Acute Coronary Syndromes

Immediate complete revascularization during the index procedure might become the new treatment paradigm in patients with an acute coronary syndrome (ACS) and multivessel disease, based on results of the BIOVASC trial.

In the trial, in patients presenting with ACS and multivessel disease, immediate complete revascularization was noninferior to staged complete revascularization for the primary composite outcome and was associated with a reduction in myocardial infarction and unplanned ischemia-driven revascularization.

The BIOVASC trial was presented on March 5 by Roberto Diletti, MD, Erasmus University Medical Center, Rotterdam, the Netherlands, at the joint scientific sessions of the American College of Cardiology and the World Heart Federation. The study was simultaneously published online in The Lancet.

“We did not detect an early safety signal against an immediate complete revascularization strategy,” the authors state in the Lancet paper, adding: “Treating physicians should not be concerned about potential risks associated with immediate treatment of nonculprit lesions.”

They note, “This strategy might be particularly effective in patients with only two-vessel disease and reasonably simple lesions, with a high likelihood of procedural success without excessive use of radiation, contrast dye, or other resources.”

The trial also showed a shorter hospital stay with an immediate complete revascularization strategy.

“Immediate complete revascularization might have potential health economic benefits because of the lower rate of myocardial infarction, including spontaneous myocardial infarction, and unplanned revascularizations, and the shorter overall hospital stay,” the researchers conclude.

Introducing his presentation, Dr. Diletti explained that multiple studies have established the clinical benefit of complete coronary revascularization as compared with exclusive reperfusion of the culprit lesion, but the optimal timing for nonculprit lesion revascularization remains unclear.

The BIOVASC trial, conducted in Belgium, Italy, the Netherlands, and Spain, involved 1,525 patients with ST-segment elevation MI (STEMI) or non-STEMI ACS and multivessel coronary artery disease with a clearly identifiable culprit lesion.

They were randomly assigned to undergo immediate complete revascularization (percutaneous coronary intervention [PCI] of the culprit lesion first, followed by other nonculprit lesions deemed to be clinically significant by the operator during the index procedure) or staged complete revascularization (PCI of only the culprit lesion during the index procedure and PCI of all nonculprit lesions deemed to be clinically significant within 6 weeks after the index procedure).

The primary outcome was the composite of all-cause mortality, MI, any unplanned ischemia-driven revascularization, or cerebrovascular events at 1 year after the index procedure.

The trial had a noninferiority design, with noninferiority of immediate to staged complete revascularization considered to be met if the upper boundary of the 95% confidence interval of the hazard ratio for the primary outcome did not exceed 1.39.

Among the trial population, 40% of patients had STEMI, 52% had non-STEMI, and 8% had unstable angina.

In the immediate complete revascularization group, 16 patients did not receive complete revascularization during the index procedure primarily because of prolonged procedure time, procedural complexity, or excessive contrast dye use. 

In the staged group, 30% of patients underwent all subsequent procedures during the index hospitalization.

Results showed that the primary composite outcome at 1 year occurred in 7.6% of the immediate revascularization group and in 9.4% of the staged group, meeting the noninferiority criteria (HR, 0.78; 95% CI, 0.55-1.11; P for noninferiority = .0011).

Superiority of the immediate over the staged complete revascularization strategy was not met at 1-year follow-up (P for superiority = .17).

However, in the prespecified analysis of clinical events at 30 days after the index procedure, immediate complete revascularization was superior to staged revascularization in terms of the composite primary outcome (2.2% vs. 5.8%; HR, 0.38; P for superiority = .0007).

One-year results showed no difference in all-cause death between the two groups, but the immediate complete revascularization group appeared to have a reduction in MI (1.9% vs. 4.5%)  and fewer unplanned ischemia-driven revascularizations (4.2% vs. 6.7%).

The difference in MI was mainly driven by spontaneous MIs (not procedure related) that predominantly occurred in the time window between the index procedure and the planned date for the staged intervention, and an originally nonculprit lesion was identified as the cause for these events in almost all cases.

Subgroup analysis showed similar results across the patient population, including age, sex, and STEMI vs. non-STEMI presentation.

High rate of MI in staged group

Discussant of the study at the ACC session, Dipti Itchhaporia, MD, University of California, Irvine, said this was a “very important trial.”  

She expressed surprise over the “remarkably high rate” of MI in the staged procedure group and asked Dr. Diletti why that might have occurred.

He responded that the operator may have misjudged the culprit lesion or that patients with ACS may have multiple unstable plaques and “treating the culprit lesion alone does not do the job.”

He added: “We need to look at the data more thoroughly to better understand this, but in both scenarios, immediate complete revascularization would prevent these events.” 

Dr. Itchhaporia also pointed out a low rate of functional imaging used in the study.  

Dr. Diletti replied that this reflected current European practice, but he acknowledged that, “in my opinion this reduces our ability to detect the culprit lesion.”

Commenting at an ACC press conference, David Moliterno, MD, Gill Heart and Vascular Institute, Lexington, Ky., said the trial poses the question  “Can we fix it all at once?” and the results suggest “Yes, we can.”

He said this approach had the advantage of removing any uncertainly as to which was the culprit lesion. “We just fix everything – leave no blockage behind.”

But he pointed out that for  some patients this may not be appropriate, such as those with compromised renal function, in whom excessive amounts of contrast material should be avoided.

CABG still needs to be considered

In a comment accompanying the Lancet publication, Tobias Pustjens, MD, Pieter Vriesendorp, MD, and Arnoud W.J. van’t Hof, MD, Cardiovascular Research Institute Maastricht (the Netherlands), note that more than half of the patients presenting with an ACS have multivessel coronary disease. 

They say the trial results suggest that “pursuing an immediate complete revascularisation strategy, especially in times of reduced hospital capacity and staff scarcity, not only benefits the individual patient in clinical outcomes but can also safely reduce the pressure on health care systems.”

But they also point out that the possibility of coronary artery bypass grafting (CABG) should not be omitted, and that CABG is still the treatment of choice in patients with diabetes or complex coronary artery disease.

They conclude: “The results of the BIOVASC study move clinical practice forward from culprit-only to an immediate, complete revascularisation strategy. … However, further fine tuning of this treatment strategy to substantiate a role for intracoronary physiology assessment, intracoronary imaging, and guidance of the heart team decision is needed.”

The BIOVASC trial was supported by an unrestricted research grant from Biotronik AG. Dr. Diletti has received institutional research grants from Biotronik, Medtronic, ACIST Medical Systems, and Boston Scientific. Dr. van’t Hof has received institutional research grants from Biotronik.

A version of this article first appeared on Medscape.com.

Immediate complete revascularization during the index procedure might become the new treatment paradigm in patients with an acute coronary syndrome (ACS) and multivessel disease, based on results of the BIOVASC trial.

In the trial, in patients presenting with ACS and multivessel disease, immediate complete revascularization was noninferior to staged complete revascularization for the primary composite outcome and was associated with a reduction in myocardial infarction and unplanned ischemia-driven revascularization.

The BIOVASC trial was presented on March 5 by Roberto Diletti, MD, Erasmus University Medical Center, Rotterdam, the Netherlands, at the joint scientific sessions of the American College of Cardiology and the World Heart Federation. The study was simultaneously published online in The Lancet.

“We did not detect an early safety signal against an immediate complete revascularization strategy,” the authors state in the Lancet paper, adding: “Treating physicians should not be concerned about potential risks associated with immediate treatment of nonculprit lesions.”

They note, “This strategy might be particularly effective in patients with only two-vessel disease and reasonably simple lesions, with a high likelihood of procedural success without excessive use of radiation, contrast dye, or other resources.”

The trial also showed a shorter hospital stay with an immediate complete revascularization strategy.

“Immediate complete revascularization might have potential health economic benefits because of the lower rate of myocardial infarction, including spontaneous myocardial infarction, and unplanned revascularizations, and the shorter overall hospital stay,” the researchers conclude.

Introducing his presentation, Dr. Diletti explained that multiple studies have established the clinical benefit of complete coronary revascularization as compared with exclusive reperfusion of the culprit lesion, but the optimal timing for nonculprit lesion revascularization remains unclear.

The BIOVASC trial, conducted in Belgium, Italy, the Netherlands, and Spain, involved 1,525 patients with ST-segment elevation MI (STEMI) or non-STEMI ACS and multivessel coronary artery disease with a clearly identifiable culprit lesion.

They were randomly assigned to undergo immediate complete revascularization (percutaneous coronary intervention [PCI] of the culprit lesion first, followed by other nonculprit lesions deemed to be clinically significant by the operator during the index procedure) or staged complete revascularization (PCI of only the culprit lesion during the index procedure and PCI of all nonculprit lesions deemed to be clinically significant within 6 weeks after the index procedure).

The primary outcome was the composite of all-cause mortality, MI, any unplanned ischemia-driven revascularization, or cerebrovascular events at 1 year after the index procedure.

The trial had a noninferiority design, with noninferiority of immediate to staged complete revascularization considered to be met if the upper boundary of the 95% confidence interval of the hazard ratio for the primary outcome did not exceed 1.39.

Among the trial population, 40% of patients had STEMI, 52% had non-STEMI, and 8% had unstable angina.

In the immediate complete revascularization group, 16 patients did not receive complete revascularization during the index procedure primarily because of prolonged procedure time, procedural complexity, or excessive contrast dye use. 

In the staged group, 30% of patients underwent all subsequent procedures during the index hospitalization.

Results showed that the primary composite outcome at 1 year occurred in 7.6% of the immediate revascularization group and in 9.4% of the staged group, meeting the noninferiority criteria (HR, 0.78; 95% CI, 0.55-1.11; P for noninferiority = .0011).

Superiority of the immediate over the staged complete revascularization strategy was not met at 1-year follow-up (P for superiority = .17).

However, in the prespecified analysis of clinical events at 30 days after the index procedure, immediate complete revascularization was superior to staged revascularization in terms of the composite primary outcome (2.2% vs. 5.8%; HR, 0.38; P for superiority = .0007).

One-year results showed no difference in all-cause death between the two groups, but the immediate complete revascularization group appeared to have a reduction in MI (1.9% vs. 4.5%)  and fewer unplanned ischemia-driven revascularizations (4.2% vs. 6.7%).

The difference in MI was mainly driven by spontaneous MIs (not procedure related) that predominantly occurred in the time window between the index procedure and the planned date for the staged intervention, and an originally nonculprit lesion was identified as the cause for these events in almost all cases.

Subgroup analysis showed similar results across the patient population, including age, sex, and STEMI vs. non-STEMI presentation.

High rate of MI in staged group

Discussant of the study at the ACC session, Dipti Itchhaporia, MD, University of California, Irvine, said this was a “very important trial.”  

She expressed surprise over the “remarkably high rate” of MI in the staged procedure group and asked Dr. Diletti why that might have occurred.

He responded that the operator may have misjudged the culprit lesion or that patients with ACS may have multiple unstable plaques and “treating the culprit lesion alone does not do the job.”

He added: “We need to look at the data more thoroughly to better understand this, but in both scenarios, immediate complete revascularization would prevent these events.” 

Dr. Itchhaporia also pointed out a low rate of functional imaging used in the study.  

Dr. Diletti replied that this reflected current European practice, but he acknowledged that, “in my opinion this reduces our ability to detect the culprit lesion.”

Commenting at an ACC press conference, David Moliterno, MD, Gill Heart and Vascular Institute, Lexington, Ky., said the trial poses the question  “Can we fix it all at once?” and the results suggest “Yes, we can.”

He said this approach had the advantage of removing any uncertainly as to which was the culprit lesion. “We just fix everything – leave no blockage behind.”

But he pointed out that for  some patients this may not be appropriate, such as those with compromised renal function, in whom excessive amounts of contrast material should be avoided.

CABG still needs to be considered

In a comment accompanying the Lancet publication, Tobias Pustjens, MD, Pieter Vriesendorp, MD, and Arnoud W.J. van’t Hof, MD, Cardiovascular Research Institute Maastricht (the Netherlands), note that more than half of the patients presenting with an ACS have multivessel coronary disease. 

They say the trial results suggest that “pursuing an immediate complete revascularisation strategy, especially in times of reduced hospital capacity and staff scarcity, not only benefits the individual patient in clinical outcomes but can also safely reduce the pressure on health care systems.”

But they also point out that the possibility of coronary artery bypass grafting (CABG) should not be omitted, and that CABG is still the treatment of choice in patients with diabetes or complex coronary artery disease.

They conclude: “The results of the BIOVASC study move clinical practice forward from culprit-only to an immediate, complete revascularisation strategy. … However, further fine tuning of this treatment strategy to substantiate a role for intracoronary physiology assessment, intracoronary imaging, and guidance of the heart team decision is needed.”

The BIOVASC trial was supported by an unrestricted research grant from Biotronik AG. Dr. Diletti has received institutional research grants from Biotronik, Medtronic, ACIST Medical Systems, and Boston Scientific. Dr. van’t Hof has received institutional research grants from Biotronik.

A version of this article first appeared on Medscape.com.

Immediate complete revascularization during the index procedure might become the new treatment paradigm in patients with an acute coronary syndrome (ACS) and multivessel disease, based on results of the BIOVASC trial.

In the trial, in patients presenting with ACS and multivessel disease, immediate complete revascularization was noninferior to staged complete revascularization for the primary composite outcome and was associated with a reduction in myocardial infarction and unplanned ischemia-driven revascularization.

The BIOVASC trial was presented on March 5 by Roberto Diletti, MD, Erasmus University Medical Center, Rotterdam, the Netherlands, at the joint scientific sessions of the American College of Cardiology and the World Heart Federation. The study was simultaneously published online in The Lancet.

“We did not detect an early safety signal against an immediate complete revascularization strategy,” the authors state in the Lancet paper, adding: “Treating physicians should not be concerned about potential risks associated with immediate treatment of nonculprit lesions.”

They note, “This strategy might be particularly effective in patients with only two-vessel disease and reasonably simple lesions, with a high likelihood of procedural success without excessive use of radiation, contrast dye, or other resources.”

The trial also showed a shorter hospital stay with an immediate complete revascularization strategy.

“Immediate complete revascularization might have potential health economic benefits because of the lower rate of myocardial infarction, including spontaneous myocardial infarction, and unplanned revascularizations, and the shorter overall hospital stay,” the researchers conclude.

Introducing his presentation, Dr. Diletti explained that multiple studies have established the clinical benefit of complete coronary revascularization as compared with exclusive reperfusion of the culprit lesion, but the optimal timing for nonculprit lesion revascularization remains unclear.

The BIOVASC trial, conducted in Belgium, Italy, the Netherlands, and Spain, involved 1,525 patients with ST-segment elevation MI (STEMI) or non-STEMI ACS and multivessel coronary artery disease with a clearly identifiable culprit lesion.

They were randomly assigned to undergo immediate complete revascularization (percutaneous coronary intervention [PCI] of the culprit lesion first, followed by other nonculprit lesions deemed to be clinically significant by the operator during the index procedure) or staged complete revascularization (PCI of only the culprit lesion during the index procedure and PCI of all nonculprit lesions deemed to be clinically significant within 6 weeks after the index procedure).

The primary outcome was the composite of all-cause mortality, MI, any unplanned ischemia-driven revascularization, or cerebrovascular events at 1 year after the index procedure.

The trial had a noninferiority design, with noninferiority of immediate to staged complete revascularization considered to be met if the upper boundary of the 95% confidence interval of the hazard ratio for the primary outcome did not exceed 1.39.

Among the trial population, 40% of patients had STEMI, 52% had non-STEMI, and 8% had unstable angina.

In the immediate complete revascularization group, 16 patients did not receive complete revascularization during the index procedure primarily because of prolonged procedure time, procedural complexity, or excessive contrast dye use. 

In the staged group, 30% of patients underwent all subsequent procedures during the index hospitalization.

Results showed that the primary composite outcome at 1 year occurred in 7.6% of the immediate revascularization group and in 9.4% of the staged group, meeting the noninferiority criteria (HR, 0.78; 95% CI, 0.55-1.11; P for noninferiority = .0011).

Superiority of the immediate over the staged complete revascularization strategy was not met at 1-year follow-up (P for superiority = .17).

However, in the prespecified analysis of clinical events at 30 days after the index procedure, immediate complete revascularization was superior to staged revascularization in terms of the composite primary outcome (2.2% vs. 5.8%; HR, 0.38; P for superiority = .0007).

One-year results showed no difference in all-cause death between the two groups, but the immediate complete revascularization group appeared to have a reduction in MI (1.9% vs. 4.5%)  and fewer unplanned ischemia-driven revascularizations (4.2% vs. 6.7%).

The difference in MI was mainly driven by spontaneous MIs (not procedure related) that predominantly occurred in the time window between the index procedure and the planned date for the staged intervention, and an originally nonculprit lesion was identified as the cause for these events in almost all cases.

Subgroup analysis showed similar results across the patient population, including age, sex, and STEMI vs. non-STEMI presentation.

High rate of MI in staged group

Discussant of the study at the ACC session, Dipti Itchhaporia, MD, University of California, Irvine, said this was a “very important trial.”  

She expressed surprise over the “remarkably high rate” of MI in the staged procedure group and asked Dr. Diletti why that might have occurred.

He responded that the operator may have misjudged the culprit lesion or that patients with ACS may have multiple unstable plaques and “treating the culprit lesion alone does not do the job.”

He added: “We need to look at the data more thoroughly to better understand this, but in both scenarios, immediate complete revascularization would prevent these events.” 

Dr. Itchhaporia also pointed out a low rate of functional imaging used in the study.  

Dr. Diletti replied that this reflected current European practice, but he acknowledged that, “in my opinion this reduces our ability to detect the culprit lesion.”

Commenting at an ACC press conference, David Moliterno, MD, Gill Heart and Vascular Institute, Lexington, Ky., said the trial poses the question  “Can we fix it all at once?” and the results suggest “Yes, we can.”

He said this approach had the advantage of removing any uncertainly as to which was the culprit lesion. “We just fix everything – leave no blockage behind.”

But he pointed out that for  some patients this may not be appropriate, such as those with compromised renal function, in whom excessive amounts of contrast material should be avoided.

CABG still needs to be considered

In a comment accompanying the Lancet publication, Tobias Pustjens, MD, Pieter Vriesendorp, MD, and Arnoud W.J. van’t Hof, MD, Cardiovascular Research Institute Maastricht (the Netherlands), note that more than half of the patients presenting with an ACS have multivessel coronary disease. 

They say the trial results suggest that “pursuing an immediate complete revascularisation strategy, especially in times of reduced hospital capacity and staff scarcity, not only benefits the individual patient in clinical outcomes but can also safely reduce the pressure on health care systems.”

But they also point out that the possibility of coronary artery bypass grafting (CABG) should not be omitted, and that CABG is still the treatment of choice in patients with diabetes or complex coronary artery disease.

They conclude: “The results of the BIOVASC study move clinical practice forward from culprit-only to an immediate, complete revascularisation strategy. … However, further fine tuning of this treatment strategy to substantiate a role for intracoronary physiology assessment, intracoronary imaging, and guidance of the heart team decision is needed.”

The BIOVASC trial was supported by an unrestricted research grant from Biotronik AG. Dr. Diletti has received institutional research grants from Biotronik, Medtronic, ACIST Medical Systems, and Boston Scientific. Dr. van’t Hof has received institutional research grants from Biotronik.

A version of this article first appeared on Medscape.com.

NEW ORLEANS – In patients undergoing percutaneous intervention (PCI) for complex coronary lesions, intravascular imaging is superior to angiography for reducing the risk of target lesion failure (TLF), according to results of a randomized trial.

Previous studies have produced the same conclusion, but the advantage was demonstrated this time in a multicenter well-powered randomized trial, principal investigator Joo Yong Hahn, MD, PhD, said at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.

Ted Bosworth/MDedge News

The earlier studies “were not definitive,” said Dr. Hahn, pointing out that even those that were randomized lacked sufficient duration of follow-up or were not inclusive of a broad array of types of complex PCI.

In this clinical outcomes–driven study, called RENOVATE-COMPLEX-PCI, 1,639 patients undergoing complex PCI in 20 South Korean treatment centers were randomized in a 2:1 ratio to PCI guided by intravascular imaging or angiography alone. There were nine types of complex PCI eligible for trial entry, including bifurcated lesions, long lesions (expected stent length ≥ 38 mm), total coronary occlusions, lesions requiring multiple stents, severely calcified lesions, and lesions in multiple vessels.

Intravascular imaging in the experimental arm could be performed with either intravascular ultrasound (IVUS) or optical coherence tomography (OCT), according to Dr. Hahn. Because one might be better than the other for specific patient and lesions characteristics, the type of intravascular imaging in the experimental group was selected at the discretion of the treating investigator, reported Dr. Hahn, of the Heart Vascular Stroke Institute, Samsung Medical Center, Sungkyunkwan University, Seoul.

The primary TLF endpoint was defined as death from cardiovascular causes, target-vessel-related MI, and target-vessel revascularization.

Risk reduction of > 35% observed

After a median of 2.1 years of follow-up, the lower TLF incidence in the group with PCI guided by intravascular imaging (7.7% vs. 12.3%) translated into a 36% reduction in risk (hazard ratio, 0.64; P = .008).

Intravascular imaging was associated with a numerical reduction of each component of TLF. In the case of death from cardiovascular causes, the confidence interval remained below the line of unity (HR 0.47; 95% CI, 0.24-0.93).

Although this was not true for target vessel–related MI (HR, 0.74, 95% CI, 0.45-1.22) or target vessel revascularization (HR, 0.66; 95% CI, 0.36-1.22), it was also true of TLF without procedural-related MI (HR, 0.59; 95% CI, 0.39-0.90) and cardiac death or target vessel–related MI (HR, 0.63; 95% CI, 0.42-0.93).

With few exceptions, all of the secondary outcomes “moved in the right direction” to favor intravascular imaging, including death from any cause (HR 0.71, 95% CI, 0.44-1.15), reported Dr. Hahn, who noted that the results were simultaneously published in the New England Journal of Medicine.

When compared, there were no major baseline differences in the 1,092 patients with PCI guided by intravascular imaging relative to the 547 guided by angiography. The median age was 65.5 years. Most (79%) were male. About half (51%) had an acute coronary syndrome and the remainder had stable ischemic heart disease. The proportions of patients with hypertension (61%), dyslipidemia (51%), and diabetes (38%) were substantial. About 18% of patients were current smokers, 24% had a previous PCI, and 7% had a previous MI.

Stent types were similar in the two groups, and they were delivered by radial access. Procedural success was achieved in about 98% of both groups. Almost all patients were discharged on a statin, aspirin, and a P2Y₁₂ inhibitor, and the other specific postprocedural medications were comparable in the two groups.

Advantage of intravascular imaging consistent

Of the complex lesions, most (55%) had diffuse long coronary artery lesions, but other types of complex PCI, including bifurcated lesions (22%), chronic total occlusions (20%), severely calcified lesions (14%), and ostial lesions of a major coronary artery (15%) were represented. Across these lesion types, intravascular imaging was favored over angiography for TLF at least numerically. The potential exceptions were lesions requiring at least three stents (HR, 1.24; 95% CI, 0.49-3.18), but confidence intervals were wide.

The trial was unblinded, but Dr. Hahn reported that imaging analyses were performed at a core laboratory and events were adjudicated by a committee with members unaware of trial group assignments.

One unanswered question is cost. Because intravascular imaging adds cost to PCI relative to angiography, cost-effectiveness analyses are needed to provide context for the decision to use this approach in all complex PCI patients. These analyses are planned.

Based on the consistency of these trial results with previous studies, almost all of which showed the same thing, “the intravascular imaging world has spoken,” said Wayne B. Batchelor, MD, director of interventional cardiology, Inova Heart and Vascular Institute, Fairfax, Va. “The only question now is when will the interventional community is going to listen.”

Ted Bosworth/MDedge News

Dr. Batchelor predicted that these data will change the mindset of many practitioners “to shift the debate to why not do it [intravascular imaging] from why do it.”

“Only about 15% of PCI is performed with intravascular imaging in the United States, and these [results] argue that this number needs to go up,” Dr. Batchelor said. Although he said there are technical reasons, such as diffuse lesions or small vessels, that prevent intravascular imaging from being used in every complex patient, he suggested the data are compelling.

“If you apply this to the one million patients undergoing PCI in the United States, this will translate potentially into tens of thousands of patients protected from the TVF endpoint,” Dr. Batchelor said.

Dr. Hahn reports no potential conflicts of interest, but this investigator-initiated trial received funding from Boston Scientific and Abbott Vascular. Dr. Batchelor reports financial relationships with Abbott Vascular, Boston Scientific, Idorsia, Medtronic, and V-Wave Medical.

NEW ORLEANS – In patients undergoing percutaneous intervention (PCI) for complex coronary lesions, intravascular imaging is superior to angiography for reducing the risk of target lesion failure (TLF), according to results of a randomized trial.

Previous studies have produced the same conclusion, but the advantage was demonstrated this time in a multicenter well-powered randomized trial, principal investigator Joo Yong Hahn, MD, PhD, said at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.

Ted Bosworth/MDedge News

The earlier studies “were not definitive,” said Dr. Hahn, pointing out that even those that were randomized lacked sufficient duration of follow-up or were not inclusive of a broad array of types of complex PCI.

In this clinical outcomes–driven study, called RENOVATE-COMPLEX-PCI, 1,639 patients undergoing complex PCI in 20 South Korean treatment centers were randomized in a 2:1 ratio to PCI guided by intravascular imaging or angiography alone. There were nine types of complex PCI eligible for trial entry, including bifurcated lesions, long lesions (expected stent length ≥ 38 mm), total coronary occlusions, lesions requiring multiple stents, severely calcified lesions, and lesions in multiple vessels.

Intravascular imaging in the experimental arm could be performed with either intravascular ultrasound (IVUS) or optical coherence tomography (OCT), according to Dr. Hahn. Because one might be better than the other for specific patient and lesions characteristics, the type of intravascular imaging in the experimental group was selected at the discretion of the treating investigator, reported Dr. Hahn, of the Heart Vascular Stroke Institute, Samsung Medical Center, Sungkyunkwan University, Seoul.

The primary TLF endpoint was defined as death from cardiovascular causes, target-vessel-related MI, and target-vessel revascularization.

Risk reduction of > 35% observed

After a median of 2.1 years of follow-up, the lower TLF incidence in the group with PCI guided by intravascular imaging (7.7% vs. 12.3%) translated into a 36% reduction in risk (hazard ratio, 0.64; P = .008).

Intravascular imaging was associated with a numerical reduction of each component of TLF. In the case of death from cardiovascular causes, the confidence interval remained below the line of unity (HR 0.47; 95% CI, 0.24-0.93).

Although this was not true for target vessel–related MI (HR, 0.74, 95% CI, 0.45-1.22) or target vessel revascularization (HR, 0.66; 95% CI, 0.36-1.22), it was also true of TLF without procedural-related MI (HR, 0.59; 95% CI, 0.39-0.90) and cardiac death or target vessel–related MI (HR, 0.63; 95% CI, 0.42-0.93).

With few exceptions, all of the secondary outcomes “moved in the right direction” to favor intravascular imaging, including death from any cause (HR 0.71, 95% CI, 0.44-1.15), reported Dr. Hahn, who noted that the results were simultaneously published in the New England Journal of Medicine.

When compared, there were no major baseline differences in the 1,092 patients with PCI guided by intravascular imaging relative to the 547 guided by angiography. The median age was 65.5 years. Most (79%) were male. About half (51%) had an acute coronary syndrome and the remainder had stable ischemic heart disease. The proportions of patients with hypertension (61%), dyslipidemia (51%), and diabetes (38%) were substantial. About 18% of patients were current smokers, 24% had a previous PCI, and 7% had a previous MI.

Stent types were similar in the two groups, and they were delivered by radial access. Procedural success was achieved in about 98% of both groups. Almost all patients were discharged on a statin, aspirin, and a P2Y₁₂ inhibitor, and the other specific postprocedural medications were comparable in the two groups.

Advantage of intravascular imaging consistent

Of the complex lesions, most (55%) had diffuse long coronary artery lesions, but other types of complex PCI, including bifurcated lesions (22%), chronic total occlusions (20%), severely calcified lesions (14%), and ostial lesions of a major coronary artery (15%) were represented. Across these lesion types, intravascular imaging was favored over angiography for TLF at least numerically. The potential exceptions were lesions requiring at least three stents (HR, 1.24; 95% CI, 0.49-3.18), but confidence intervals were wide.

The trial was unblinded, but Dr. Hahn reported that imaging analyses were performed at a core laboratory and events were adjudicated by a committee with members unaware of trial group assignments.

One unanswered question is cost. Because intravascular imaging adds cost to PCI relative to angiography, cost-effectiveness analyses are needed to provide context for the decision to use this approach in all complex PCI patients. These analyses are planned.

Based on the consistency of these trial results with previous studies, almost all of which showed the same thing, “the intravascular imaging world has spoken,” said Wayne B. Batchelor, MD, director of interventional cardiology, Inova Heart and Vascular Institute, Fairfax, Va. “The only question now is when will the interventional community is going to listen.”

Ted Bosworth/MDedge News

Dr. Batchelor predicted that these data will change the mindset of many practitioners “to shift the debate to why not do it [intravascular imaging] from why do it.”

“Only about 15% of PCI is performed with intravascular imaging in the United States, and these [results] argue that this number needs to go up,” Dr. Batchelor said. Although he said there are technical reasons, such as diffuse lesions or small vessels, that prevent intravascular imaging from being used in every complex patient, he suggested the data are compelling.

“If you apply this to the one million patients undergoing PCI in the United States, this will translate potentially into tens of thousands of patients protected from the TVF endpoint,” Dr. Batchelor said.

Dr. Hahn reports no potential conflicts of interest, but this investigator-initiated trial received funding from Boston Scientific and Abbott Vascular. Dr. Batchelor reports financial relationships with Abbott Vascular, Boston Scientific, Idorsia, Medtronic, and V-Wave Medical.

NEW ORLEANS – In patients undergoing percutaneous intervention (PCI) for complex coronary lesions, intravascular imaging is superior to angiography for reducing the risk of target lesion failure (TLF), according to results of a randomized trial.

Previous studies have produced the same conclusion, but the advantage was demonstrated this time in a multicenter well-powered randomized trial, principal investigator Joo Yong Hahn, MD, PhD, said at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.

Ted Bosworth/MDedge News

The earlier studies “were not definitive,” said Dr. Hahn, pointing out that even those that were randomized lacked sufficient duration of follow-up or were not inclusive of a broad array of types of complex PCI.

In this clinical outcomes–driven study, called RENOVATE-COMPLEX-PCI, 1,639 patients undergoing complex PCI in 20 South Korean treatment centers were randomized in a 2:1 ratio to PCI guided by intravascular imaging or angiography alone. There were nine types of complex PCI eligible for trial entry, including bifurcated lesions, long lesions (expected stent length ≥ 38 mm), total coronary occlusions, lesions requiring multiple stents, severely calcified lesions, and lesions in multiple vessels.

Intravascular imaging in the experimental arm could be performed with either intravascular ultrasound (IVUS) or optical coherence tomography (OCT), according to Dr. Hahn. Because one might be better than the other for specific patient and lesions characteristics, the type of intravascular imaging in the experimental group was selected at the discretion of the treating investigator, reported Dr. Hahn, of the Heart Vascular Stroke Institute, Samsung Medical Center, Sungkyunkwan University, Seoul.

The primary TLF endpoint was defined as death from cardiovascular causes, target-vessel-related MI, and target-vessel revascularization.

Risk reduction of > 35% observed

After a median of 2.1 years of follow-up, the lower TLF incidence in the group with PCI guided by intravascular imaging (7.7% vs. 12.3%) translated into a 36% reduction in risk (hazard ratio, 0.64; P = .008).

Intravascular imaging was associated with a numerical reduction of each component of TLF. In the case of death from cardiovascular causes, the confidence interval remained below the line of unity (HR 0.47; 95% CI, 0.24-0.93).

Although this was not true for target vessel–related MI (HR, 0.74, 95% CI, 0.45-1.22) or target vessel revascularization (HR, 0.66; 95% CI, 0.36-1.22), it was also true of TLF without procedural-related MI (HR, 0.59; 95% CI, 0.39-0.90) and cardiac death or target vessel–related MI (HR, 0.63; 95% CI, 0.42-0.93).

With few exceptions, all of the secondary outcomes “moved in the right direction” to favor intravascular imaging, including death from any cause (HR 0.71, 95% CI, 0.44-1.15), reported Dr. Hahn, who noted that the results were simultaneously published in the New England Journal of Medicine.

When compared, there were no major baseline differences in the 1,092 patients with PCI guided by intravascular imaging relative to the 547 guided by angiography. The median age was 65.5 years. Most (79%) were male. About half (51%) had an acute coronary syndrome and the remainder had stable ischemic heart disease. The proportions of patients with hypertension (61%), dyslipidemia (51%), and diabetes (38%) were substantial. About 18% of patients were current smokers, 24% had a previous PCI, and 7% had a previous MI.

Stent types were similar in the two groups, and they were delivered by radial access. Procedural success was achieved in about 98% of both groups. Almost all patients were discharged on a statin, aspirin, and a P2Y₁₂ inhibitor, and the other specific postprocedural medications were comparable in the two groups.

Advantage of intravascular imaging consistent

Of the complex lesions, most (55%) had diffuse long coronary artery lesions, but other types of complex PCI, including bifurcated lesions (22%), chronic total occlusions (20%), severely calcified lesions (14%), and ostial lesions of a major coronary artery (15%) were represented. Across these lesion types, intravascular imaging was favored over angiography for TLF at least numerically. The potential exceptions were lesions requiring at least three stents (HR, 1.24; 95% CI, 0.49-3.18), but confidence intervals were wide.

The trial was unblinded, but Dr. Hahn reported that imaging analyses were performed at a core laboratory and events were adjudicated by a committee with members unaware of trial group assignments.

One unanswered question is cost. Because intravascular imaging adds cost to PCI relative to angiography, cost-effectiveness analyses are needed to provide context for the decision to use this approach in all complex PCI patients. These analyses are planned.

Based on the consistency of these trial results with previous studies, almost all of which showed the same thing, “the intravascular imaging world has spoken,” said Wayne B. Batchelor, MD, director of interventional cardiology, Inova Heart and Vascular Institute, Fairfax, Va. “The only question now is when will the interventional community is going to listen.”

Ted Bosworth/MDedge News

Dr. Batchelor predicted that these data will change the mindset of many practitioners “to shift the debate to why not do it [intravascular imaging] from why do it.”

“Only about 15% of PCI is performed with intravascular imaging in the United States, and these [results] argue that this number needs to go up,” Dr. Batchelor said. Although he said there are technical reasons, such as diffuse lesions or small vessels, that prevent intravascular imaging from being used in every complex patient, he suggested the data are compelling.

“If you apply this to the one million patients undergoing PCI in the United States, this will translate potentially into tens of thousands of patients protected from the TVF endpoint,” Dr. Batchelor said.

Dr. Hahn reports no potential conflicts of interest, but this investigator-initiated trial received funding from Boston Scientific and Abbott Vascular. Dr. Batchelor reports financial relationships with Abbott Vascular, Boston Scientific, Idorsia, Medtronic, and V-Wave Medical.

There is no magical amount of viable ventricular myocardium that makes percutaneous coronary intervention (PCI) an effective addition to optimal medical therapy (OMT) in stable patients with coronary disease and poor ventricular function, suggests an analysis from a major trial.

The REVIVED-BCIS2 trial recently made waves when it showed no clinical advantage from adding PCI to OMT in stable patients with severe ischemic left ventricular (LV) dysfunction. All the patients had shown viable but dysfunctional myocardium that could potentially be revascularized.

But in a secondary analysis, extent of such hibernating heart muscle was not a good predictor of clinical outcomes, which in the trial meant death from any cause or hospitalization for heart failure (HHF).

Burden of myocardial scar tissue, however, turned out to be a potent predictor of clinical risk regardless of coronary disease severity or even LV ejection fraction (LVEF).

Because myocardial viability tracks poorly with outcomes in patients like those enrolled in the trial, as the new analysis suggests, conventional viability testing isn’t an effective guide for deciding who among them should get PCI, Divaka Perera, MD, said in an interview.

Dr. Perera, of King’s College London and the trial’s principal investigator, presented the REVIVED-BCIS2 secondary results at the joint scientific sessions of the American College of Cardiology and the World Heart Federation..

Viability testing for ischemia, he noted, is often used in practice to aid revascularization decisions. As the extent of myocardial viability can vary, it’s been asked – ever since the trial’s primary publication – whether there could be “a sweet spot or Goldilocks zone of viability that would allow prediction of which patients will do better with PCI compared to medical therapy,” Dr. Perera said. “The trial conclusively shows that is not the case.”

That the extent of hibernating myocardium, which is viable but dysfunctional, didn’t predict clinical outcomes or LV functional recovery “is disruptive of current practice and challenges a view that’s been held for decades.”

The trial’s 700 patients receiving OMT had been randomly assigned to undergo PCI or not, 347 and 353 patients, respectively. About 12% of the total were women.

About 70% of patients underwent baseline and follow-up myocardial viability testing using cardiac magnetic resonance (CMR) imaging with late gadolinium enhancement for estimation of scar burden; the remainder underwent dobutamine-stress echocardiography. All imaging assessments were conducted at independent core laboratories, Dr. Perera reported.

Extent of myocardial viability was defined three ways: volume of hibernating heart muscle, total volume of viable myocardium, and scar burden – all expressed as a percentage of total LV volume.

Every 10% increment in LV volume found to be hibernating related to a hazard ratio of 0.98 (95% confidence interval, 0.93-1.04; P = .56) for all-cause mortality or HHF at a median of 3.3 years. The analysis was adjusted for age, sex, diabetes, previous HHF, chronic renal failure, extent of CAD, type of viability testing, and baseline LVEF.

The adjusted HR for the same percentage increment in total viable myocardium was marginally significantly reduced at 0.93 (95% CI, 0.87-1.00; P = .048).

The correlation with scar burden was stronger. The adjusted composite-endpoint HR per 10% increment in scar burden was significantly increased at 1.18 (95% CI, 1.04-1.33; P = .009).

Extent of myocardial viability by tertiles, regardless of viability definition, did not highlight any group with a reduced risk for death or HHF, or group with better LV functional recovery, from OMT plus PCI, compared with OMT alone.

The findings appear to suggest that scar burden, but not extent of viability as it’s usually measured, may effectively guide PCI decisions in such patients, Dr. Perera said.

“I would say that viability testing as we understand it now, based on the paradigm of hibernating myocardium, is very useful,” he said, “but that is not the only information we can get from a viability test.”

Scar burden can also be determined from the same tests but isn’t typically looked at. “We’re actually collecting this information  but not using it,” Dr. Perera said. “When we do, it is really powerfully predictive” of both clinical outcomes and LV functional recovery. “Yet scar burden is not in any of the guidelines for stratifying risk.”

REVIVED-BCIS2 was funded by the National Institute for Health and Care Research Health Technology Assessment Program. Dr. Perera had no disclosures.

A version of this article first appeared on Medscape.com.

There is no magical amount of viable ventricular myocardium that makes percutaneous coronary intervention (PCI) an effective addition to optimal medical therapy (OMT) in stable patients with coronary disease and poor ventricular function, suggests an analysis from a major trial.

The REVIVED-BCIS2 trial recently made waves when it showed no clinical advantage from adding PCI to OMT in stable patients with severe ischemic left ventricular (LV) dysfunction. All the patients had shown viable but dysfunctional myocardium that could potentially be revascularized.

But in a secondary analysis, extent of such hibernating heart muscle was not a good predictor of clinical outcomes, which in the trial meant death from any cause or hospitalization for heart failure (HHF).

Burden of myocardial scar tissue, however, turned out to be a potent predictor of clinical risk regardless of coronary disease severity or even LV ejection fraction (LVEF).

Because myocardial viability tracks poorly with outcomes in patients like those enrolled in the trial, as the new analysis suggests, conventional viability testing isn’t an effective guide for deciding who among them should get PCI, Divaka Perera, MD, said in an interview.

Dr. Perera, of King’s College London and the trial’s principal investigator, presented the REVIVED-BCIS2 secondary results at the joint scientific sessions of the American College of Cardiology and the World Heart Federation..

Viability testing for ischemia, he noted, is often used in practice to aid revascularization decisions. As the extent of myocardial viability can vary, it’s been asked – ever since the trial’s primary publication – whether there could be “a sweet spot or Goldilocks zone of viability that would allow prediction of which patients will do better with PCI compared to medical therapy,” Dr. Perera said. “The trial conclusively shows that is not the case.”

That the extent of hibernating myocardium, which is viable but dysfunctional, didn’t predict clinical outcomes or LV functional recovery “is disruptive of current practice and challenges a view that’s been held for decades.”

The trial’s 700 patients receiving OMT had been randomly assigned to undergo PCI or not, 347 and 353 patients, respectively. About 12% of the total were women.

About 70% of patients underwent baseline and follow-up myocardial viability testing using cardiac magnetic resonance (CMR) imaging with late gadolinium enhancement for estimation of scar burden; the remainder underwent dobutamine-stress echocardiography. All imaging assessments were conducted at independent core laboratories, Dr. Perera reported.

Extent of myocardial viability was defined three ways: volume of hibernating heart muscle, total volume of viable myocardium, and scar burden – all expressed as a percentage of total LV volume.

Every 10% increment in LV volume found to be hibernating related to a hazard ratio of 0.98 (95% confidence interval, 0.93-1.04; P = .56) for all-cause mortality or HHF at a median of 3.3 years. The analysis was adjusted for age, sex, diabetes, previous HHF, chronic renal failure, extent of CAD, type of viability testing, and baseline LVEF.

The adjusted HR for the same percentage increment in total viable myocardium was marginally significantly reduced at 0.93 (95% CI, 0.87-1.00; P = .048).

The correlation with scar burden was stronger. The adjusted composite-endpoint HR per 10% increment in scar burden was significantly increased at 1.18 (95% CI, 1.04-1.33; P = .009).

Extent of myocardial viability by tertiles, regardless of viability definition, did not highlight any group with a reduced risk for death or HHF, or group with better LV functional recovery, from OMT plus PCI, compared with OMT alone.

The findings appear to suggest that scar burden, but not extent of viability as it’s usually measured, may effectively guide PCI decisions in such patients, Dr. Perera said.

“I would say that viability testing as we understand it now, based on the paradigm of hibernating myocardium, is very useful,” he said, “but that is not the only information we can get from a viability test.”

Scar burden can also be determined from the same tests but isn’t typically looked at. “We’re actually collecting this information  but not using it,” Dr. Perera said. “When we do, it is really powerfully predictive” of both clinical outcomes and LV functional recovery. “Yet scar burden is not in any of the guidelines for stratifying risk.”

REVIVED-BCIS2 was funded by the National Institute for Health and Care Research Health Technology Assessment Program. Dr. Perera had no disclosures.

A version of this article first appeared on Medscape.com.

There is no magical amount of viable ventricular myocardium that makes percutaneous coronary intervention (PCI) an effective addition to optimal medical therapy (OMT) in stable patients with coronary disease and poor ventricular function, suggests an analysis from a major trial.

The REVIVED-BCIS2 trial recently made waves when it showed no clinical advantage from adding PCI to OMT in stable patients with severe ischemic left ventricular (LV) dysfunction. All the patients had shown viable but dysfunctional myocardium that could potentially be revascularized.

But in a secondary analysis, extent of such hibernating heart muscle was not a good predictor of clinical outcomes, which in the trial meant death from any cause or hospitalization for heart failure (HHF).

Burden of myocardial scar tissue, however, turned out to be a potent predictor of clinical risk regardless of coronary disease severity or even LV ejection fraction (LVEF).

Because myocardial viability tracks poorly with outcomes in patients like those enrolled in the trial, as the new analysis suggests, conventional viability testing isn’t an effective guide for deciding who among them should get PCI, Divaka Perera, MD, said in an interview.

Dr. Perera, of King’s College London and the trial’s principal investigator, presented the REVIVED-BCIS2 secondary results at the joint scientific sessions of the American College of Cardiology and the World Heart Federation..

Viability testing for ischemia, he noted, is often used in practice to aid revascularization decisions. As the extent of myocardial viability can vary, it’s been asked – ever since the trial’s primary publication – whether there could be “a sweet spot or Goldilocks zone of viability that would allow prediction of which patients will do better with PCI compared to medical therapy,” Dr. Perera said. “The trial conclusively shows that is not the case.”

That the extent of hibernating myocardium, which is viable but dysfunctional, didn’t predict clinical outcomes or LV functional recovery “is disruptive of current practice and challenges a view that’s been held for decades.”

The trial’s 700 patients receiving OMT had been randomly assigned to undergo PCI or not, 347 and 353 patients, respectively. About 12% of the total were women.

About 70% of patients underwent baseline and follow-up myocardial viability testing using cardiac magnetic resonance (CMR) imaging with late gadolinium enhancement for estimation of scar burden; the remainder underwent dobutamine-stress echocardiography. All imaging assessments were conducted at independent core laboratories, Dr. Perera reported.

Extent of myocardial viability was defined three ways: volume of hibernating heart muscle, total volume of viable myocardium, and scar burden – all expressed as a percentage of total LV volume.

Every 10% increment in LV volume found to be hibernating related to a hazard ratio of 0.98 (95% confidence interval, 0.93-1.04; P = .56) for all-cause mortality or HHF at a median of 3.3 years. The analysis was adjusted for age, sex, diabetes, previous HHF, chronic renal failure, extent of CAD, type of viability testing, and baseline LVEF.

The adjusted HR for the same percentage increment in total viable myocardium was marginally significantly reduced at 0.93 (95% CI, 0.87-1.00; P = .048).

The correlation with scar burden was stronger. The adjusted composite-endpoint HR per 10% increment in scar burden was significantly increased at 1.18 (95% CI, 1.04-1.33; P = .009).

Extent of myocardial viability by tertiles, regardless of viability definition, did not highlight any group with a reduced risk for death or HHF, or group with better LV functional recovery, from OMT plus PCI, compared with OMT alone.

The findings appear to suggest that scar burden, but not extent of viability as it’s usually measured, may effectively guide PCI decisions in such patients, Dr. Perera said.

“I would say that viability testing as we understand it now, based on the paradigm of hibernating myocardium, is very useful,” he said, “but that is not the only information we can get from a viability test.”

Scar burden can also be determined from the same tests but isn’t typically looked at. “We’re actually collecting this information  but not using it,” Dr. Perera said. “When we do, it is really powerfully predictive” of both clinical outcomes and LV functional recovery. “Yet scar burden is not in any of the guidelines for stratifying risk.”

REVIVED-BCIS2 was funded by the National Institute for Health and Care Research Health Technology Assessment Program. Dr. Perera had no disclosures.

A version of this article first appeared on Medscape.com.

A new approach to lowering cholesterol with the use of bempedoic acid (Nexletol, Esperion) brought about a significant reduction in cardiovascular events in patients intolerant to statins in the large phase 3, placebo-controlled CLEAR Outcomes trial.

The drug lowered LDL cholesterol by 21% in the study and reduced the composite primary endpoint, including cardiovascular death, MI, stroke, or coronary revascularization, by 13%; MI was reduced by 23% and coronary revascularization, by 19%.

The drug was also well tolerated in the mixed population of primary and secondary prevention patients unable or unwilling to take statins.

Mitchel L. Zoler/MDedge News

“These findings establish bempedoic acid as an effective approach to reduce major cardiovascular events in statin-intolerant patients,” study chair, Steven E. Nissen, MD, of the Cleveland Clinic concluded.

Dr. Nissen presented the CLEAR Outcomes trial at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.

The study was simultaneously published online in the New England Journal of Medicine. Top-line results were previously reported in December 2022.

Dr. Nissen pointed out that, while in the current study bempedoic acid was studied as monotherapy, he believes the drug will mainly be used in clinical practice in combination with ezetimibe, a combination shown to reduce LDL by 38%. “I think this is how it will be used in clinical practice. So, we can get an almost 40% LDL reduction – that’s about the same as 40 mg simvastatin or 20 mg atorvastatin – without giving a statin. And I think that’s where I see the potential of this therapy,” he said.

Dr. Nissen described statin intolerance as “a vexing problem” that prevents many patients from achieving LDL cholesterol levels associated with cardiovascular benefits.

He explained that bempedoic acid, an adenosine triphosphate citrate lyase inhibitor, inhibits hepatic cholesterol synthesis upstream of hydroxymethylglutaryl coenzyme A reductase, the enzyme inhibited by statins. Bempedoic acid is a prodrug activated in the liver, but not in peripheral tissues, resulting in a low incidence of muscle-related adverse events. Although bempedoic acid is approved for lowering LDL cholesterol, this is the first trial to assess its effects on cardiovascular outcomes.
 

CLEAR Outcomes

The CLEAR Outcomes trial included 13,970 patients (48% women) from 32 countries who were unable or unwilling to take statins owing to unacceptable adverse effects and who had, or were at high risk for, cardiovascular disease. They were randomly assigned to oral bempedoic acid, 180 mg daily, or placebo.

The mean LDL cholesterol level at baseline was 139 mg/dL in both groups, and after 6 months, the reduction in the level was greater with bempedoic acid than with placebo by 29.2 mg/dL (a 21.1% reduction).

The drug was also associated with a 22% reduction in high-sensitivity C-reactive protein.

After a median duration of follow-up of 40.6 months, the incidence of a primary endpoint (cardiovascular death, MI, stroke, or coronary revascularization) was significantly lower (by 13%) with bempedoic acid than with placebo (11.7% vs. 13.3%; hazard ratio, 0.87; P = .004).

The absolute risk reduction was 1.6 percentage points, and the number needed to treat for 40 months to prevent one event was 63.

The secondary composite endpoint of cardiovascular death/stroke/MI was reduced by 15% (8.2% vs. 9.5%; HR, 0.85; P = .006). Fatal or nonfatal MI was reduced by 23% (3.7% vs. 4.8%; HR, 0.77; P = .002), and coronary revascularization was reduced by 19% (6.2% vs. 7.6%; HR, 0.81; P = .001).

Bempedoic acid had no significant effects on fatal or nonfatal stroke, death from cardiovascular causes, and death from any cause.

Subgroup analysis showed similar results across all groups and no difference in treatment effect between men and women.

Adverse events were reported by 25% of patients in both groups, with adverse events leading to discontinuation reported by 10.8% of the bempedoic acid group and 10.4% of the placebo group.

Muscle disorders were reported in 15.0% of the bempedoic acid group versus 15.4% of the placebo group. And there was also no difference in new cases of diabetes (16.1% vs. 17.1%).

Bempedoic acid was associated with small increases in the incidence of gout (3.1% vs. 2.1%) and cholelithiasis (2.2% vs. 1.2%), and also small increases in serum creatinine, uric acid, and hepatic enzyme levels.

In the NEJM article, the authors pointed out that the concept of statin intolerance remains controversial. Some recent studies suggested that reported adverse effects represent an anticipation of harm, often described as the “nocebo” effect.

“Whether real or perceived, statin intolerance remains a vexing clinical problem that can prevent patients who are guideline eligible for statin treatment from reaching LDL cholesterol levels associated with clinical benefits. Accordingly, alternative nonstatin therapies are needed to manage the LDL cholesterol level in these patients,” they wrote.

“Management of patients unable or unwilling to take statins represents a challenging and frustrating clinical issue. Regardless whether this problem represents the ‘nocebo’ effect or actual intolerance, these high-risk patients need effective alternative therapies,” Dr. Nissen concluded. “The CLEAR Outcomes trial provides a sound rationale for use of bempedoic acid to reduce major adverse cardiovascular outcomes in patients intolerant to statins.”
 

‘Compelling findings’

Discussing the trial at the ACC late-breaking clinical trial session, Michelle O’Donoghue, MD, Brigham and Women’s Hospital, Boston, noted that this is the largest trial to date in statin-intolerant patients.

She pointed out that although the issue of statin intolerance remains controversial, adherence to statins is often not good, so this is an important patient population to study.

She said it was “quite remarkable” that 48% of the study were women, adding: “There is still much that we need to understand about why women appear to be less willing or able to tolerate statin therapy.” 

Dr. O’Donoghue concluded that the study showed “compelling findings,” and the event reduction was in line with what would be expected from the LDL cholesterol reduction, further supporting the LDL cholesterol hypothesis. 

She added: “Bempedoic acid is an important addition to our arsenal of nonstatin LDL-lowering therapies. And while it was overall well tolerated, it did not get a complete free pass, as there were some modest safety concerns.”

In an editorial accompanying the NEJM publication, John Alexander, MD, Duke Clinical Research Institute, Durham, N.C., wrote: “The compelling results of the CLEAR Outcomes trial will and should increase the use of bempedoic acid in patients with established atherosclerotic vascular disease and in those at high risk for vascular disease who are unable or unwilling to take statins.”

He warned, however, that it is premature to consider bempedoic acid as an alternative to statins. “Given the overwhelming evidence of the vascular benefits of statins, clinicians should continue their efforts to prescribe them at the maximum tolerated doses for appropriate patients, including those who may have discontinued statins because of presumed side effects.”.

Dr. Alexander also pointed out that although bempedoic acid also reduces the LDL cholesterol level in patients taking statins, the clinical benefits of bempedoic acid added to standard statin therapy are unknown. 

On the observation that bempedoic acid had no observed effect on mortality, he noted that “Many individual trials of statins have also not shown an effect of the agent on mortality; it was only through the meta-analysis of multiple clinical trials that the effects of statins on mortality became clear.”

“Bempedoic acid has now entered the list of evidence-based alternatives to statins for primary and secondary prevention in patients at high cardiovascular risk,” Dr. Alexander concluded. “The benefits of bempedoic acid are now clearer, and it is now our responsibility to translate this information into better primary and secondary prevention for more at-risk patients, who will, as a result, benefit from fewer cardiovascular events.”

In a second editorial, John F. Keaney Jr., MD, Brigham and Women’s Hospital, said the lack of a clear association between bempedoic acid and muscle disorders, new-onset diabetes, or worsening hyperglycemia is “welcome news” for statin-intolerant patients.

But he cautioned that “these data must be interpreted cautiously, because bempedoic acid, when combined with a statin, appears to enhance the occurrence of muscle symptoms. Moreover, bempedoic acid has its own reported side effects, including tendon rupture, increased uric acid levels, gout, and reduced glomerular filtration rate, which are not seen with statin use.”

In terms of drug interactions, Dr. Keaney noted that bempedoic acid can increase the circulating levels of simvastatin and pravastatin, so it should not be used in patients who are receiving these agents at doses above 20 mg and 40 mg, respectively. Similarly, bempedoic acid should not be used with fibrates other than fenofibrate because of concerns regarding cholelithiasis.

“Available data clearly indicate that bempedoic acid can be used as an adjunct to statin and nonstatin therapies (except as noted above) to produce an additional 16%-26% reduction in the LDL cholesterol level,” he added. “However, it is not yet clear to what extent adjunctive bempedoic acid will further reduce the risk of cardiovascular events.”

The CLEAR Outcomes trial was supported by Esperion Therapeutics. Dr. Nissen reported receiving grants from AbbVie, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Esperion, Novartis, and Silence Pharmaceuticals and consultancies with Amgen and Glenmark Pharmaceuticals.

A version of this article first appeared on Medscape.com.

A new approach to lowering cholesterol with the use of bempedoic acid (Nexletol, Esperion) brought about a significant reduction in cardiovascular events in patients intolerant to statins in the large phase 3, placebo-controlled CLEAR Outcomes trial.

The drug lowered LDL cholesterol by 21% in the study and reduced the composite primary endpoint, including cardiovascular death, MI, stroke, or coronary revascularization, by 13%; MI was reduced by 23% and coronary revascularization, by 19%.

The drug was also well tolerated in the mixed population of primary and secondary prevention patients unable or unwilling to take statins.

Mitchel L. Zoler/MDedge News

“These findings establish bempedoic acid as an effective approach to reduce major cardiovascular events in statin-intolerant patients,” study chair, Steven E. Nissen, MD, of the Cleveland Clinic concluded.

Dr. Nissen presented the CLEAR Outcomes trial at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.

The study was simultaneously published online in the New England Journal of Medicine. Top-line results were previously reported in December 2022.

Dr. Nissen pointed out that, while in the current study bempedoic acid was studied as monotherapy, he believes the drug will mainly be used in clinical practice in combination with ezetimibe, a combination shown to reduce LDL by 38%. “I think this is how it will be used in clinical practice. So, we can get an almost 40% LDL reduction – that’s about the same as 40 mg simvastatin or 20 mg atorvastatin – without giving a statin. And I think that’s where I see the potential of this therapy,” he said.

Dr. Nissen described statin intolerance as “a vexing problem” that prevents many patients from achieving LDL cholesterol levels associated with cardiovascular benefits.

He explained that bempedoic acid, an adenosine triphosphate citrate lyase inhibitor, inhibits hepatic cholesterol synthesis upstream of hydroxymethylglutaryl coenzyme A reductase, the enzyme inhibited by statins. Bempedoic acid is a prodrug activated in the liver, but not in peripheral tissues, resulting in a low incidence of muscle-related adverse events. Although bempedoic acid is approved for lowering LDL cholesterol, this is the first trial to assess its effects on cardiovascular outcomes.
 

CLEAR Outcomes

The CLEAR Outcomes trial included 13,970 patients (48% women) from 32 countries who were unable or unwilling to take statins owing to unacceptable adverse effects and who had, or were at high risk for, cardiovascular disease. They were randomly assigned to oral bempedoic acid, 180 mg daily, or placebo.

The mean LDL cholesterol level at baseline was 139 mg/dL in both groups, and after 6 months, the reduction in the level was greater with bempedoic acid than with placebo by 29.2 mg/dL (a 21.1% reduction).

The drug was also associated with a 22% reduction in high-sensitivity C-reactive protein.

After a median duration of follow-up of 40.6 months, the incidence of a primary endpoint (cardiovascular death, MI, stroke, or coronary revascularization) was significantly lower (by 13%) with bempedoic acid than with placebo (11.7% vs. 13.3%; hazard ratio, 0.87; P = .004).

The absolute risk reduction was 1.6 percentage points, and the number needed to treat for 40 months to prevent one event was 63.

The secondary composite endpoint of cardiovascular death/stroke/MI was reduced by 15% (8.2% vs. 9.5%; HR, 0.85; P = .006). Fatal or nonfatal MI was reduced by 23% (3.7% vs. 4.8%; HR, 0.77; P = .002), and coronary revascularization was reduced by 19% (6.2% vs. 7.6%; HR, 0.81; P = .001).

Bempedoic acid had no significant effects on fatal or nonfatal stroke, death from cardiovascular causes, and death from any cause.

Subgroup analysis showed similar results across all groups and no difference in treatment effect between men and women.

Adverse events were reported by 25% of patients in both groups, with adverse events leading to discontinuation reported by 10.8% of the bempedoic acid group and 10.4% of the placebo group.

Muscle disorders were reported in 15.0% of the bempedoic acid group versus 15.4% of the placebo group. And there was also no difference in new cases of diabetes (16.1% vs. 17.1%).

Bempedoic acid was associated with small increases in the incidence of gout (3.1% vs. 2.1%) and cholelithiasis (2.2% vs. 1.2%), and also small increases in serum creatinine, uric acid, and hepatic enzyme levels.

In the NEJM article, the authors pointed out that the concept of statin intolerance remains controversial. Some recent studies suggested that reported adverse effects represent an anticipation of harm, often described as the “nocebo” effect.

“Whether real or perceived, statin intolerance remains a vexing clinical problem that can prevent patients who are guideline eligible for statin treatment from reaching LDL cholesterol levels associated with clinical benefits. Accordingly, alternative nonstatin therapies are needed to manage the LDL cholesterol level in these patients,” they wrote.

“Management of patients unable or unwilling to take statins represents a challenging and frustrating clinical issue. Regardless whether this problem represents the ‘nocebo’ effect or actual intolerance, these high-risk patients need effective alternative therapies,” Dr. Nissen concluded. “The CLEAR Outcomes trial provides a sound rationale for use of bempedoic acid to reduce major adverse cardiovascular outcomes in patients intolerant to statins.”
 

‘Compelling findings’

Discussing the trial at the ACC late-breaking clinical trial session, Michelle O’Donoghue, MD, Brigham and Women’s Hospital, Boston, noted that this is the largest trial to date in statin-intolerant patients.

She pointed out that although the issue of statin intolerance remains controversial, adherence to statins is often not good, so this is an important patient population to study.

She said it was “quite remarkable” that 48% of the study were women, adding: “There is still much that we need to understand about why women appear to be less willing or able to tolerate statin therapy.” 

Dr. O’Donoghue concluded that the study showed “compelling findings,” and the event reduction was in line with what would be expected from the LDL cholesterol reduction, further supporting the LDL cholesterol hypothesis. 

She added: “Bempedoic acid is an important addition to our arsenal of nonstatin LDL-lowering therapies. And while it was overall well tolerated, it did not get a complete free pass, as there were some modest safety concerns.”

In an editorial accompanying the NEJM publication, John Alexander, MD, Duke Clinical Research Institute, Durham, N.C., wrote: “The compelling results of the CLEAR Outcomes trial will and should increase the use of bempedoic acid in patients with established atherosclerotic vascular disease and in those at high risk for vascular disease who are unable or unwilling to take statins.”

He warned, however, that it is premature to consider bempedoic acid as an alternative to statins. “Given the overwhelming evidence of the vascular benefits of statins, clinicians should continue their efforts to prescribe them at the maximum tolerated doses for appropriate patients, including those who may have discontinued statins because of presumed side effects.”.

Dr. Alexander also pointed out that although bempedoic acid also reduces the LDL cholesterol level in patients taking statins, the clinical benefits of bempedoic acid added to standard statin therapy are unknown. 

On the observation that bempedoic acid had no observed effect on mortality, he noted that “Many individual trials of statins have also not shown an effect of the agent on mortality; it was only through the meta-analysis of multiple clinical trials that the effects of statins on mortality became clear.”

“Bempedoic acid has now entered the list of evidence-based alternatives to statins for primary and secondary prevention in patients at high cardiovascular risk,” Dr. Alexander concluded. “The benefits of bempedoic acid are now clearer, and it is now our responsibility to translate this information into better primary and secondary prevention for more at-risk patients, who will, as a result, benefit from fewer cardiovascular events.”

In a second editorial, John F. Keaney Jr., MD, Brigham and Women’s Hospital, said the lack of a clear association between bempedoic acid and muscle disorders, new-onset diabetes, or worsening hyperglycemia is “welcome news” for statin-intolerant patients.

But he cautioned that “these data must be interpreted cautiously, because bempedoic acid, when combined with a statin, appears to enhance the occurrence of muscle symptoms. Moreover, bempedoic acid has its own reported side effects, including tendon rupture, increased uric acid levels, gout, and reduced glomerular filtration rate, which are not seen with statin use.”

In terms of drug interactions, Dr. Keaney noted that bempedoic acid can increase the circulating levels of simvastatin and pravastatin, so it should not be used in patients who are receiving these agents at doses above 20 mg and 40 mg, respectively. Similarly, bempedoic acid should not be used with fibrates other than fenofibrate because of concerns regarding cholelithiasis.

“Available data clearly indicate that bempedoic acid can be used as an adjunct to statin and nonstatin therapies (except as noted above) to produce an additional 16%-26% reduction in the LDL cholesterol level,” he added. “However, it is not yet clear to what extent adjunctive bempedoic acid will further reduce the risk of cardiovascular events.”

The CLEAR Outcomes trial was supported by Esperion Therapeutics. Dr. Nissen reported receiving grants from AbbVie, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Esperion, Novartis, and Silence Pharmaceuticals and consultancies with Amgen and Glenmark Pharmaceuticals.

A version of this article first appeared on Medscape.com.

A new approach to lowering cholesterol with the use of bempedoic acid (Nexletol, Esperion) brought about a significant reduction in cardiovascular events in patients intolerant to statins in the large phase 3, placebo-controlled CLEAR Outcomes trial.

The drug lowered LDL cholesterol by 21% in the study and reduced the composite primary endpoint, including cardiovascular death, MI, stroke, or coronary revascularization, by 13%; MI was reduced by 23% and coronary revascularization, by 19%.

The drug was also well tolerated in the mixed population of primary and secondary prevention patients unable or unwilling to take statins.

Mitchel L. Zoler/MDedge News

“These findings establish bempedoic acid as an effective approach to reduce major cardiovascular events in statin-intolerant patients,” study chair, Steven E. Nissen, MD, of the Cleveland Clinic concluded.

Dr. Nissen presented the CLEAR Outcomes trial at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.

The study was simultaneously published online in the New England Journal of Medicine. Top-line results were previously reported in December 2022.

Dr. Nissen pointed out that, while in the current study bempedoic acid was studied as monotherapy, he believes the drug will mainly be used in clinical practice in combination with ezetimibe, a combination shown to reduce LDL by 38%. “I think this is how it will be used in clinical practice. So, we can get an almost 40% LDL reduction – that’s about the same as 40 mg simvastatin or 20 mg atorvastatin – without giving a statin. And I think that’s where I see the potential of this therapy,” he said.

Dr. Nissen described statin intolerance as “a vexing problem” that prevents many patients from achieving LDL cholesterol levels associated with cardiovascular benefits.

He explained that bempedoic acid, an adenosine triphosphate citrate lyase inhibitor, inhibits hepatic cholesterol synthesis upstream of hydroxymethylglutaryl coenzyme A reductase, the enzyme inhibited by statins. Bempedoic acid is a prodrug activated in the liver, but not in peripheral tissues, resulting in a low incidence of muscle-related adverse events. Although bempedoic acid is approved for lowering LDL cholesterol, this is the first trial to assess its effects on cardiovascular outcomes.
 

CLEAR Outcomes

The CLEAR Outcomes trial included 13,970 patients (48% women) from 32 countries who were unable or unwilling to take statins owing to unacceptable adverse effects and who had, or were at high risk for, cardiovascular disease. They were randomly assigned to oral bempedoic acid, 180 mg daily, or placebo.

The mean LDL cholesterol level at baseline was 139 mg/dL in both groups, and after 6 months, the reduction in the level was greater with bempedoic acid than with placebo by 29.2 mg/dL (a 21.1% reduction).

The drug was also associated with a 22% reduction in high-sensitivity C-reactive protein.

After a median duration of follow-up of 40.6 months, the incidence of a primary endpoint (cardiovascular death, MI, stroke, or coronary revascularization) was significantly lower (by 13%) with bempedoic acid than with placebo (11.7% vs. 13.3%; hazard ratio, 0.87; P = .004).

The absolute risk reduction was 1.6 percentage points, and the number needed to treat for 40 months to prevent one event was 63.

The secondary composite endpoint of cardiovascular death/stroke/MI was reduced by 15% (8.2% vs. 9.5%; HR, 0.85; P = .006). Fatal or nonfatal MI was reduced by 23% (3.7% vs. 4.8%; HR, 0.77; P = .002), and coronary revascularization was reduced by 19% (6.2% vs. 7.6%; HR, 0.81; P = .001).

Bempedoic acid had no significant effects on fatal or nonfatal stroke, death from cardiovascular causes, and death from any cause.

Subgroup analysis showed similar results across all groups and no difference in treatment effect between men and women.

Adverse events were reported by 25% of patients in both groups, with adverse events leading to discontinuation reported by 10.8% of the bempedoic acid group and 10.4% of the placebo group.

Muscle disorders were reported in 15.0% of the bempedoic acid group versus 15.4% of the placebo group. And there was also no difference in new cases of diabetes (16.1% vs. 17.1%).

Bempedoic acid was associated with small increases in the incidence of gout (3.1% vs. 2.1%) and cholelithiasis (2.2% vs. 1.2%), and also small increases in serum creatinine, uric acid, and hepatic enzyme levels.

In the NEJM article, the authors pointed out that the concept of statin intolerance remains controversial. Some recent studies suggested that reported adverse effects represent an anticipation of harm, often described as the “nocebo” effect.

“Whether real or perceived, statin intolerance remains a vexing clinical problem that can prevent patients who are guideline eligible for statin treatment from reaching LDL cholesterol levels associated with clinical benefits. Accordingly, alternative nonstatin therapies are needed to manage the LDL cholesterol level in these patients,” they wrote.

“Management of patients unable or unwilling to take statins represents a challenging and frustrating clinical issue. Regardless whether this problem represents the ‘nocebo’ effect or actual intolerance, these high-risk patients need effective alternative therapies,” Dr. Nissen concluded. “The CLEAR Outcomes trial provides a sound rationale for use of bempedoic acid to reduce major adverse cardiovascular outcomes in patients intolerant to statins.”
 

‘Compelling findings’

Discussing the trial at the ACC late-breaking clinical trial session, Michelle O’Donoghue, MD, Brigham and Women’s Hospital, Boston, noted that this is the largest trial to date in statin-intolerant patients.

She pointed out that although the issue of statin intolerance remains controversial, adherence to statins is often not good, so this is an important patient population to study.

She said it was “quite remarkable” that 48% of the study were women, adding: “There is still much that we need to understand about why women appear to be less willing or able to tolerate statin therapy.” 

Dr. O’Donoghue concluded that the study showed “compelling findings,” and the event reduction was in line with what would be expected from the LDL cholesterol reduction, further supporting the LDL cholesterol hypothesis. 

She added: “Bempedoic acid is an important addition to our arsenal of nonstatin LDL-lowering therapies. And while it was overall well tolerated, it did not get a complete free pass, as there were some modest safety concerns.”

In an editorial accompanying the NEJM publication, John Alexander, MD, Duke Clinical Research Institute, Durham, N.C., wrote: “The compelling results of the CLEAR Outcomes trial will and should increase the use of bempedoic acid in patients with established atherosclerotic vascular disease and in those at high risk for vascular disease who are unable or unwilling to take statins.”

He warned, however, that it is premature to consider bempedoic acid as an alternative to statins. “Given the overwhelming evidence of the vascular benefits of statins, clinicians should continue their efforts to prescribe them at the maximum tolerated doses for appropriate patients, including those who may have discontinued statins because of presumed side effects.”.

Dr. Alexander also pointed out that although bempedoic acid also reduces the LDL cholesterol level in patients taking statins, the clinical benefits of bempedoic acid added to standard statin therapy are unknown. 

On the observation that bempedoic acid had no observed effect on mortality, he noted that “Many individual trials of statins have also not shown an effect of the agent on mortality; it was only through the meta-analysis of multiple clinical trials that the effects of statins on mortality became clear.”

“Bempedoic acid has now entered the list of evidence-based alternatives to statins for primary and secondary prevention in patients at high cardiovascular risk,” Dr. Alexander concluded. “The benefits of bempedoic acid are now clearer, and it is now our responsibility to translate this information into better primary and secondary prevention for more at-risk patients, who will, as a result, benefit from fewer cardiovascular events.”

In a second editorial, John F. Keaney Jr., MD, Brigham and Women’s Hospital, said the lack of a clear association between bempedoic acid and muscle disorders, new-onset diabetes, or worsening hyperglycemia is “welcome news” for statin-intolerant patients.

But he cautioned that “these data must be interpreted cautiously, because bempedoic acid, when combined with a statin, appears to enhance the occurrence of muscle symptoms. Moreover, bempedoic acid has its own reported side effects, including tendon rupture, increased uric acid levels, gout, and reduced glomerular filtration rate, which are not seen with statin use.”

In terms of drug interactions, Dr. Keaney noted that bempedoic acid can increase the circulating levels of simvastatin and pravastatin, so it should not be used in patients who are receiving these agents at doses above 20 mg and 40 mg, respectively. Similarly, bempedoic acid should not be used with fibrates other than fenofibrate because of concerns regarding cholelithiasis.

“Available data clearly indicate that bempedoic acid can be used as an adjunct to statin and nonstatin therapies (except as noted above) to produce an additional 16%-26% reduction in the LDL cholesterol level,” he added. “However, it is not yet clear to what extent adjunctive bempedoic acid will further reduce the risk of cardiovascular events.”

The CLEAR Outcomes trial was supported by Esperion Therapeutics. Dr. Nissen reported receiving grants from AbbVie, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Esperion, Novartis, and Silence Pharmaceuticals and consultancies with Amgen and Glenmark Pharmaceuticals.

A version of this article first appeared on Medscape.com.

In a pooled analysis from two randomized trials, transcatheter aortic valve implantation (TAVI) was associated with significantly less bioprosthetic valve dysfunction (BVD) than a surgical prosthetic implantation, according to data presented as a late-breaker at the Cardiovascular Research Technologies conference, sponsored by MedStar Heart & Vascular Institute.

“The difference in valve performance was driven by a twofold lower SVD [structural valve deterioration] and a 3-fold lower severe PPM [prothesis-patient mismatch] for TAVI versus surgery,” reported Steven J. Yakubov, MD.

Ted Bosworth/MDedge News

The data were pooled from the CoreValve U.S. Pivotal and SURTAVI randomized trials. Of patients participating in these two trials, 5-year follow-up data were available for 1,128 randomized to the CoreValve/Evolut TAVI and 971 randomized to surgical prosthetic valve replacement.

The major focus of the study was on the cumulative incidence of BVD, but the study also included separate analyses on the relationship between BVD and clinical outcomes. Preprocedural indicators for BVD at 5 years were also analyzed.

SVD was defined as a mean gradient increase of at least 10 mm Hg from discharge to 30 days, along with at least 20 mm Hg at last echo or new-onset aortic regurgitation. Nonstructural valve deterioration (NSVD) was defined as severe PPM at discharge or 30 days or severe paravalvular regurgitation through 5 years. In addition to these two components, the BVD endpoint also included thrombosis and endocarditis.
 

Surgical valve deterioration high at 5 years

On the basis of these definitions, the rate of BVD at 5 years was 14.2% in the surgery group and 7.8% in the TAVI group, translating into a 50% risk reduction in favor of TAVI (hazard ratio, 0.50; P < .001).

Thrombosis or endocarditis occurred in low rates in both groups, but every other component of BVD favored TAVI significantly, not just numerically. This included SVD (2.2% vs. 4.4%; P = .004), and the two components of NSVD, PPM (3.7% vs. 11.8%; P < .001) and severe paravalvular regurgitation (0.2% vs. 1.2%; P = .02).

When stratified by annular diameter, the relative advantage of TAVI over surgery was greatest in those valves with diameters of up to 23 mm. In this group, the lower relative rate in the TAVI group (8.6% vs. 19.7%) represented a nearly 70% reduction in risk of valve deterioration at 5 years (HR, 0.31; P < .001).

However, the advantage at 5 years also remained substantial and significant in larger valves (8.1% vs. 12.6%), translating into a 40% risk reduction in favor of TAVI (HR, 0.60; P = .002).

Independent of type of valve replacement, BVD at 5 years was associated with worse outcomes, including significantly increased risks for all-cause mortality (HR, 1.46; P = .004), cardiovascular mortality (1.84; P < .001), and hospitalization for valve disease or worsening heart failure (HR, 1.67; P = .001).

The baseline characteristics that were statistically associated with BVD at 5 years on multivariate analysis in pooled data from both the TAVI and surgical groups included age (P = .02), a creatinine clearance less than 30 mL/min per 1.73 m² (P = .006), and a low relative baseline left ventricular ejection fraction (P < .001).
 

BVD criteria validated for outcome prediction

The four components of valve performance employed in this analysis (SVD, NSVD, thrombosis, and endocarditis) were drawn from consensus documents issued by the Valve Academic Research Consortium and the European Association of Percutaneous Cardiovascular Interventions, but the relative importance of these components for predicting valve survival was previously unknown, according to Dr. Yakubov.

“This is the first analysis to validate clinical criteria for valve performance and its association with clinical outcomes,” said Dr. Yakubov, medical director of cardiovascular studies, OhioHealth Research Institute at Riverside Methodist Hospital, Columbus.

This is also the first study to employ randomized data to prove an advantage of TAVI over surgery in long-term follow-up.

A 10-year follow-up is planned for the patients who participated in these two trials, but the lower rate of BVD in the TAVI arm at 5 years is already a threat to surgical repairs, acknowledged several surgeons who served as panelists in the session where these results were presented.

“I think that these data are a reflection of the fact that we [surgeons] are not being as aggressive as we should be,” said Gregory P. Fontana, MD, who is national director, cardiothoracic surgery, HCA Healthcare, and is affiliated with Los Robles Health System, Thousand Oaks, Calif. “We need to be employing larger prostheses.”

Ted Bosworth/MDedge News

A very similar comment was made by Michael J. Reardon, MD, a professor of cardiothoracic surgery at Houston Methodist Hospital. Pointing to the higher rate of PVL as an example of a common postsurgical complication, he agreed that surgeons should be moving to bigger valve sizes.

While adjustments in valve size might address the steeper rise in NSVD subtypes of BVD observed in the surgical group, but Dr. Reardon and others pointed out that late BVD events also rose at a greater pace in the surgical group. These suggest other improvements in technique might also be needed to keep surgical valve repairs competitive.

Dr. Yakubov reported financial relationships with Medtronic and Boston Scientific, both of which provided funding for this study. Dr. Fontana reported financial relationships with Abbott and Medtronic. Dr. Reardon reported financial relationships with Abbott, Boston Scientific, Medtronic, and Gore Medical.

In a pooled analysis from two randomized trials, transcatheter aortic valve implantation (TAVI) was associated with significantly less bioprosthetic valve dysfunction (BVD) than a surgical prosthetic implantation, according to data presented as a late-breaker at the Cardiovascular Research Technologies conference, sponsored by MedStar Heart & Vascular Institute.

“The difference in valve performance was driven by a twofold lower SVD [structural valve deterioration] and a 3-fold lower severe PPM [prothesis-patient mismatch] for TAVI versus surgery,” reported Steven J. Yakubov, MD.

Ted Bosworth/MDedge News

The data were pooled from the CoreValve U.S. Pivotal and SURTAVI randomized trials. Of patients participating in these two trials, 5-year follow-up data were available for 1,128 randomized to the CoreValve/Evolut TAVI and 971 randomized to surgical prosthetic valve replacement.

The major focus of the study was on the cumulative incidence of BVD, but the study also included separate analyses on the relationship between BVD and clinical outcomes. Preprocedural indicators for BVD at 5 years were also analyzed.

SVD was defined as a mean gradient increase of at least 10 mm Hg from discharge to 30 days, along with at least 20 mm Hg at last echo or new-onset aortic regurgitation. Nonstructural valve deterioration (NSVD) was defined as severe PPM at discharge or 30 days or severe paravalvular regurgitation through 5 years. In addition to these two components, the BVD endpoint also included thrombosis and endocarditis.
 

Surgical valve deterioration high at 5 years

On the basis of these definitions, the rate of BVD at 5 years was 14.2% in the surgery group and 7.8% in the TAVI group, translating into a 50% risk reduction in favor of TAVI (hazard ratio, 0.50; P < .001).

Thrombosis or endocarditis occurred in low rates in both groups, but every other component of BVD favored TAVI significantly, not just numerically. This included SVD (2.2% vs. 4.4%; P = .004), and the two components of NSVD, PPM (3.7% vs. 11.8%; P < .001) and severe paravalvular regurgitation (0.2% vs. 1.2%; P = .02).

When stratified by annular diameter, the relative advantage of TAVI over surgery was greatest in those valves with diameters of up to 23 mm. In this group, the lower relative rate in the TAVI group (8.6% vs. 19.7%) represented a nearly 70% reduction in risk of valve deterioration at 5 years (HR, 0.31; P < .001).

However, the advantage at 5 years also remained substantial and significant in larger valves (8.1% vs. 12.6%), translating into a 40% risk reduction in favor of TAVI (HR, 0.60; P = .002).

Independent of type of valve replacement, BVD at 5 years was associated with worse outcomes, including significantly increased risks for all-cause mortality (HR, 1.46; P = .004), cardiovascular mortality (1.84; P < .001), and hospitalization for valve disease or worsening heart failure (HR, 1.67; P = .001).

The baseline characteristics that were statistically associated with BVD at 5 years on multivariate analysis in pooled data from both the TAVI and surgical groups included age (P = .02), a creatinine clearance less than 30 mL/min per 1.73 m² (P = .006), and a low relative baseline left ventricular ejection fraction (P < .001).
 

BVD criteria validated for outcome prediction

The four components of valve performance employed in this analysis (SVD, NSVD, thrombosis, and endocarditis) were drawn from consensus documents issued by the Valve Academic Research Consortium and the European Association of Percutaneous Cardiovascular Interventions, but the relative importance of these components for predicting valve survival was previously unknown, according to Dr. Yakubov.

“This is the first analysis to validate clinical criteria for valve performance and its association with clinical outcomes,” said Dr. Yakubov, medical director of cardiovascular studies, OhioHealth Research Institute at Riverside Methodist Hospital, Columbus.

This is also the first study to employ randomized data to prove an advantage of TAVI over surgery in long-term follow-up.

A 10-year follow-up is planned for the patients who participated in these two trials, but the lower rate of BVD in the TAVI arm at 5 years is already a threat to surgical repairs, acknowledged several surgeons who served as panelists in the session where these results were presented.

“I think that these data are a reflection of the fact that we [surgeons] are not being as aggressive as we should be,” said Gregory P. Fontana, MD, who is national director, cardiothoracic surgery, HCA Healthcare, and is affiliated with Los Robles Health System, Thousand Oaks, Calif. “We need to be employing larger prostheses.”

Ted Bosworth/MDedge News

A very similar comment was made by Michael J. Reardon, MD, a professor of cardiothoracic surgery at Houston Methodist Hospital. Pointing to the higher rate of PVL as an example of a common postsurgical complication, he agreed that surgeons should be moving to bigger valve sizes.

While adjustments in valve size might address the steeper rise in NSVD subtypes of BVD observed in the surgical group, but Dr. Reardon and others pointed out that late BVD events also rose at a greater pace in the surgical group. These suggest other improvements in technique might also be needed to keep surgical valve repairs competitive.

Dr. Yakubov reported financial relationships with Medtronic and Boston Scientific, both of which provided funding for this study. Dr. Fontana reported financial relationships with Abbott and Medtronic. Dr. Reardon reported financial relationships with Abbott, Boston Scientific, Medtronic, and Gore Medical.

In a pooled analysis from two randomized trials, transcatheter aortic valve implantation (TAVI) was associated with significantly less bioprosthetic valve dysfunction (BVD) than a surgical prosthetic implantation, according to data presented as a late-breaker at the Cardiovascular Research Technologies conference, sponsored by MedStar Heart & Vascular Institute.

“The difference in valve performance was driven by a twofold lower SVD [structural valve deterioration] and a 3-fold lower severe PPM [prothesis-patient mismatch] for TAVI versus surgery,” reported Steven J. Yakubov, MD.

Ted Bosworth/MDedge News

The data were pooled from the CoreValve U.S. Pivotal and SURTAVI randomized trials. Of patients participating in these two trials, 5-year follow-up data were available for 1,128 randomized to the CoreValve/Evolut TAVI and 971 randomized to surgical prosthetic valve replacement.

The major focus of the study was on the cumulative incidence of BVD, but the study also included separate analyses on the relationship between BVD and clinical outcomes. Preprocedural indicators for BVD at 5 years were also analyzed.

SVD was defined as a mean gradient increase of at least 10 mm Hg from discharge to 30 days, along with at least 20 mm Hg at last echo or new-onset aortic regurgitation. Nonstructural valve deterioration (NSVD) was defined as severe PPM at discharge or 30 days or severe paravalvular regurgitation through 5 years. In addition to these two components, the BVD endpoint also included thrombosis and endocarditis.
 

Surgical valve deterioration high at 5 years

On the basis of these definitions, the rate of BVD at 5 years was 14.2% in the surgery group and 7.8% in the TAVI group, translating into a 50% risk reduction in favor of TAVI (hazard ratio, 0.50; P < .001).

Thrombosis or endocarditis occurred in low rates in both groups, but every other component of BVD favored TAVI significantly, not just numerically. This included SVD (2.2% vs. 4.4%; P = .004), and the two components of NSVD, PPM (3.7% vs. 11.8%; P < .001) and severe paravalvular regurgitation (0.2% vs. 1.2%; P = .02).

When stratified by annular diameter, the relative advantage of TAVI over surgery was greatest in those valves with diameters of up to 23 mm. In this group, the lower relative rate in the TAVI group (8.6% vs. 19.7%) represented a nearly 70% reduction in risk of valve deterioration at 5 years (HR, 0.31; P < .001).

However, the advantage at 5 years also remained substantial and significant in larger valves (8.1% vs. 12.6%), translating into a 40% risk reduction in favor of TAVI (HR, 0.60; P = .002).

Independent of type of valve replacement, BVD at 5 years was associated with worse outcomes, including significantly increased risks for all-cause mortality (HR, 1.46; P = .004), cardiovascular mortality (1.84; P < .001), and hospitalization for valve disease or worsening heart failure (HR, 1.67; P = .001).

The baseline characteristics that were statistically associated with BVD at 5 years on multivariate analysis in pooled data from both the TAVI and surgical groups included age (P = .02), a creatinine clearance less than 30 mL/min per 1.73 m² (P = .006), and a low relative baseline left ventricular ejection fraction (P < .001).
 

BVD criteria validated for outcome prediction

The four components of valve performance employed in this analysis (SVD, NSVD, thrombosis, and endocarditis) were drawn from consensus documents issued by the Valve Academic Research Consortium and the European Association of Percutaneous Cardiovascular Interventions, but the relative importance of these components for predicting valve survival was previously unknown, according to Dr. Yakubov.

“This is the first analysis to validate clinical criteria for valve performance and its association with clinical outcomes,” said Dr. Yakubov, medical director of cardiovascular studies, OhioHealth Research Institute at Riverside Methodist Hospital, Columbus.

This is also the first study to employ randomized data to prove an advantage of TAVI over surgery in long-term follow-up.

A 10-year follow-up is planned for the patients who participated in these two trials, but the lower rate of BVD in the TAVI arm at 5 years is already a threat to surgical repairs, acknowledged several surgeons who served as panelists in the session where these results were presented.

“I think that these data are a reflection of the fact that we [surgeons] are not being as aggressive as we should be,” said Gregory P. Fontana, MD, who is national director, cardiothoracic surgery, HCA Healthcare, and is affiliated with Los Robles Health System, Thousand Oaks, Calif. “We need to be employing larger prostheses.”

Ted Bosworth/MDedge News

A very similar comment was made by Michael J. Reardon, MD, a professor of cardiothoracic surgery at Houston Methodist Hospital. Pointing to the higher rate of PVL as an example of a common postsurgical complication, he agreed that surgeons should be moving to bigger valve sizes.

While adjustments in valve size might address the steeper rise in NSVD subtypes of BVD observed in the surgical group, but Dr. Reardon and others pointed out that late BVD events also rose at a greater pace in the surgical group. These suggest other improvements in technique might also be needed to keep surgical valve repairs competitive.

Dr. Yakubov reported financial relationships with Medtronic and Boston Scientific, both of which provided funding for this study. Dr. Fontana reported financial relationships with Abbott and Medtronic. Dr. Reardon reported financial relationships with Abbott, Boston Scientific, Medtronic, and Gore Medical.

Infections of coronary stents appear to be uncommon, but it is not clear if they are often missed, underreported, or truly rare, according to a new analysis.

In a search of multiple databases, 79 cases of coronary stent infections (CSI) were found in 65 published reports, according to Venkatakrishnan Ramakumar, MBBS, MD, department of cardiology, All India Institute of Medical Sciences, New Delhi.

Ted Bosworth/MDedge News

Over the period of evaluation, which had no defined starting point but stretched to November 2021, the 79 infections reported worldwide occurred when millions of percutaneous coronary intervention (PCI) procedures were performed. In the United States alone, the current estimated annual number of PCIs is 600,000, according to an article published in the Journal of the American Heart Association.

If the number of reported CSI cases represented even a modest fraction of those that occurred, the risk would still be almost negligible. Yet, Dr. Ramakumar insisted that there has been little attention paid to the potential for CSI, creating a situation in which many or almost all cases are simply being missed.

“We do not know how many infections have gone unrecognized,” Dr. Ramakumar said in presenting his results at the Cardiovascular Research Technologies conference, sponsored by MedStar Heart & Vascular Institute. And even if they are identified and promptly treated, there “is the potential for a publication bias,” he added, referring to the reluctance of investigators to submit and publishers to accept manuscripts with negative results.

Regardless of the frequency with which they occur, CSI is associated with bad outcomes, according to the data evaluated by Dr. Ramakumar. On the basis of in-hospital mortality, the primary endpoint of this analysis, the rate of death in patients developing CSI was 30.3%.
 

Successful treatment varied by hospital type

This risk was not uniform. Rather, rates of in-hospital mortality and proportion of patients treated successfully varied substantially by type of hospital. At private teaching hospitals for example, successful treatment – whether medical alone or followed by bailout surgery – was 80%. The rates fell to 40% at public teaching hospitals and then to 25% at private nonteaching hospitals.

The full-text articles included in this analysis were evaluated and selected by two reviewers working independently. A CSI diagnosis made clinically or with imaging and treatment outcomes were among criteria for the case studies to be included. Dr. Ramakumar said the study, which he claimed is the largest systematic review of CSI ever conducted, has been registered with PROSPERO, an international prospective registry of systematic reviews.

The presenting symptom was fever in 72% of cases and chest pain in the others, although there was one asymptomatic CSI reported. On angiography, 62% had a concomitant mycotic aneurysm. Intramyocardial abscess (13.9%), rupture (11.3%), and coronary fistula (7.5%) were also common findings, but no angiographic abnormalities could be identified in 53% of patients.

Following PCI, most CSI developed within 8 days (43%) or the first month (23%), but CSI was reported more than 6 months after the procedure in 19%. Complex PCI accounted for 51% of cases. Of stent types, 56% were drug eluting and 13% were bare metal.

When comparing characteristics of those who survived CSI with those who did not, most (89%) of those with a non–ST-segment elevated acute coronary syndrome ultimately survived, while survival from CSI in those with structural heart disease was only 17%.

Microbiological findings were not a criterion for study inclusion, but Staphylococcus species accounted for 65% of the infections for which positive cultures were reported. Pseudomonas accounted for 13%. Less than 4% (3.8%) tested positive for multiple pathogens. A small proportion of patients had unusual infectious organisms.

As part of this analysis, the investigators developed an artificial intelligence model to predict CSI based on patient characteristics and other variables. However, the specificity of only around 70% led Dr. Ramakumar to conclude that it does not yet have practical value.

However, he believes that better methodology to detect CSI is needed, and he proposed a diagnostic algorithm that he believes would both improve detection rates and accelerate the time to diagnosis.
 

Algorithm proposed for detection of CSI

In this algorithm, the first step in symptomatic patients with a positive blood culture suspected of CSI is imaging, such as transthoracic echocardiography, to identify features of infective endocarditis or endarteritis. If the imaging is positive, further imaging, such as PET, that supports the diagnosis, should be adequate to support a diagnosis and treatment.

If initial imaging is negative, alternative diagnoses should be considered, but Dr. Ramakumar advised repeat imaging after 48 hours if symptoms persist and no other causes are found.

Dr. Ramakumar acknowledged the many limitations of this analysis, including the small sample size and the challenges of assembling coherent data from case reports with variable types of information submitted during different eras of PCI evolution. However, reiterating that CSI might be frequently missed, he emphasized that this problem might be bigger than currently understood.

It is difficult to rule out any possibility that CSI is frequently missed, but Andrew Sharp, MD, PhD, a consultant interventional cardiologist at the University Hospital of Wales, Cardiff, is skeptical.

“One might think this is a potential problem, but I cannot think of one patient in whom this has occurred,” Dr. Sharp said in an interview. He is fairly confident that they are extremely rare.

“When there is infection associated with a foreign body, such as a pacemaker, they do not typically resolve by themselves,” he explained. “Often the device has to be removed. If this was true for CSI, then I think we would be aware of these complications.”

However, he praised the investigators for taking a look at CSI in a systematic approach. An invited panelist during the CRT featured research, which is where these data were presented, Dr. Sharp was more interested in understanding why they do not occur now that data are available to suggest they are rare.

“Is there something in the coronary environment, such as the consistent blood flow, that protects against infection?” he asked. CSI is a valid area of further research, according to Dr. Sharp, but he does not consider infected stents to be a common threat based on his own sizable case series.

Dr. Ramakumar and Dr. Sharp reported no potential conflicts of interest.

Infections of coronary stents appear to be uncommon, but it is not clear if they are often missed, underreported, or truly rare, according to a new analysis.

In a search of multiple databases, 79 cases of coronary stent infections (CSI) were found in 65 published reports, according to Venkatakrishnan Ramakumar, MBBS, MD, department of cardiology, All India Institute of Medical Sciences, New Delhi.

Ted Bosworth/MDedge News

Over the period of evaluation, which had no defined starting point but stretched to November 2021, the 79 infections reported worldwide occurred when millions of percutaneous coronary intervention (PCI) procedures were performed. In the United States alone, the current estimated annual number of PCIs is 600,000, according to an article published in the Journal of the American Heart Association.

If the number of reported CSI cases represented even a modest fraction of those that occurred, the risk would still be almost negligible. Yet, Dr. Ramakumar insisted that there has been little attention paid to the potential for CSI, creating a situation in which many or almost all cases are simply being missed.

“We do not know how many infections have gone unrecognized,” Dr. Ramakumar said in presenting his results at the Cardiovascular Research Technologies conference, sponsored by MedStar Heart & Vascular Institute. And even if they are identified and promptly treated, there “is the potential for a publication bias,” he added, referring to the reluctance of investigators to submit and publishers to accept manuscripts with negative results.

Regardless of the frequency with which they occur, CSI is associated with bad outcomes, according to the data evaluated by Dr. Ramakumar. On the basis of in-hospital mortality, the primary endpoint of this analysis, the rate of death in patients developing CSI was 30.3%.
 

Successful treatment varied by hospital type

This risk was not uniform. Rather, rates of in-hospital mortality and proportion of patients treated successfully varied substantially by type of hospital. At private teaching hospitals for example, successful treatment – whether medical alone or followed by bailout surgery – was 80%. The rates fell to 40% at public teaching hospitals and then to 25% at private nonteaching hospitals.

The full-text articles included in this analysis were evaluated and selected by two reviewers working independently. A CSI diagnosis made clinically or with imaging and treatment outcomes were among criteria for the case studies to be included. Dr. Ramakumar said the study, which he claimed is the largest systematic review of CSI ever conducted, has been registered with PROSPERO, an international prospective registry of systematic reviews.

The presenting symptom was fever in 72% of cases and chest pain in the others, although there was one asymptomatic CSI reported. On angiography, 62% had a concomitant mycotic aneurysm. Intramyocardial abscess (13.9%), rupture (11.3%), and coronary fistula (7.5%) were also common findings, but no angiographic abnormalities could be identified in 53% of patients.

Following PCI, most CSI developed within 8 days (43%) or the first month (23%), but CSI was reported more than 6 months after the procedure in 19%. Complex PCI accounted for 51% of cases. Of stent types, 56% were drug eluting and 13% were bare metal.

When comparing characteristics of those who survived CSI with those who did not, most (89%) of those with a non–ST-segment elevated acute coronary syndrome ultimately survived, while survival from CSI in those with structural heart disease was only 17%.

Microbiological findings were not a criterion for study inclusion, but Staphylococcus species accounted for 65% of the infections for which positive cultures were reported. Pseudomonas accounted for 13%. Less than 4% (3.8%) tested positive for multiple pathogens. A small proportion of patients had unusual infectious organisms.

As part of this analysis, the investigators developed an artificial intelligence model to predict CSI based on patient characteristics and other variables. However, the specificity of only around 70% led Dr. Ramakumar to conclude that it does not yet have practical value.

However, he believes that better methodology to detect CSI is needed, and he proposed a diagnostic algorithm that he believes would both improve detection rates and accelerate the time to diagnosis.
 

Algorithm proposed for detection of CSI

In this algorithm, the first step in symptomatic patients with a positive blood culture suspected of CSI is imaging, such as transthoracic echocardiography, to identify features of infective endocarditis or endarteritis. If the imaging is positive, further imaging, such as PET, that supports the diagnosis, should be adequate to support a diagnosis and treatment.

If initial imaging is negative, alternative diagnoses should be considered, but Dr. Ramakumar advised repeat imaging after 48 hours if symptoms persist and no other causes are found.

Dr. Ramakumar acknowledged the many limitations of this analysis, including the small sample size and the challenges of assembling coherent data from case reports with variable types of information submitted during different eras of PCI evolution. However, reiterating that CSI might be frequently missed, he emphasized that this problem might be bigger than currently understood.

It is difficult to rule out any possibility that CSI is frequently missed, but Andrew Sharp, MD, PhD, a consultant interventional cardiologist at the University Hospital of Wales, Cardiff, is skeptical.

“One might think this is a potential problem, but I cannot think of one patient in whom this has occurred,” Dr. Sharp said in an interview. He is fairly confident that they are extremely rare.

“When there is infection associated with a foreign body, such as a pacemaker, they do not typically resolve by themselves,” he explained. “Often the device has to be removed. If this was true for CSI, then I think we would be aware of these complications.”

However, he praised the investigators for taking a look at CSI in a systematic approach. An invited panelist during the CRT featured research, which is where these data were presented, Dr. Sharp was more interested in understanding why they do not occur now that data are available to suggest they are rare.

“Is there something in the coronary environment, such as the consistent blood flow, that protects against infection?” he asked. CSI is a valid area of further research, according to Dr. Sharp, but he does not consider infected stents to be a common threat based on his own sizable case series.

Dr. Ramakumar and Dr. Sharp reported no potential conflicts of interest.

Infections of coronary stents appear to be uncommon, but it is not clear if they are often missed, underreported, or truly rare, according to a new analysis.

In a search of multiple databases, 79 cases of coronary stent infections (CSI) were found in 65 published reports, according to Venkatakrishnan Ramakumar, MBBS, MD, department of cardiology, All India Institute of Medical Sciences, New Delhi.

Ted Bosworth/MDedge News

Over the period of evaluation, which had no defined starting point but stretched to November 2021, the 79 infections reported worldwide occurred when millions of percutaneous coronary intervention (PCI) procedures were performed. In the United States alone, the current estimated annual number of PCIs is 600,000, according to an article published in the Journal of the American Heart Association.

If the number of reported CSI cases represented even a modest fraction of those that occurred, the risk would still be almost negligible. Yet, Dr. Ramakumar insisted that there has been little attention paid to the potential for CSI, creating a situation in which many or almost all cases are simply being missed.

“We do not know how many infections have gone unrecognized,” Dr. Ramakumar said in presenting his results at the Cardiovascular Research Technologies conference, sponsored by MedStar Heart & Vascular Institute. And even if they are identified and promptly treated, there “is the potential for a publication bias,” he added, referring to the reluctance of investigators to submit and publishers to accept manuscripts with negative results.

Regardless of the frequency with which they occur, CSI is associated with bad outcomes, according to the data evaluated by Dr. Ramakumar. On the basis of in-hospital mortality, the primary endpoint of this analysis, the rate of death in patients developing CSI was 30.3%.
 

Successful treatment varied by hospital type

This risk was not uniform. Rather, rates of in-hospital mortality and proportion of patients treated successfully varied substantially by type of hospital. At private teaching hospitals for example, successful treatment – whether medical alone or followed by bailout surgery – was 80%. The rates fell to 40% at public teaching hospitals and then to 25% at private nonteaching hospitals.

The full-text articles included in this analysis were evaluated and selected by two reviewers working independently. A CSI diagnosis made clinically or with imaging and treatment outcomes were among criteria for the case studies to be included. Dr. Ramakumar said the study, which he claimed is the largest systematic review of CSI ever conducted, has been registered with PROSPERO, an international prospective registry of systematic reviews.

The presenting symptom was fever in 72% of cases and chest pain in the others, although there was one asymptomatic CSI reported. On angiography, 62% had a concomitant mycotic aneurysm. Intramyocardial abscess (13.9%), rupture (11.3%), and coronary fistula (7.5%) were also common findings, but no angiographic abnormalities could be identified in 53% of patients.

Following PCI, most CSI developed within 8 days (43%) or the first month (23%), but CSI was reported more than 6 months after the procedure in 19%. Complex PCI accounted for 51% of cases. Of stent types, 56% were drug eluting and 13% were bare metal.

When comparing characteristics of those who survived CSI with those who did not, most (89%) of those with a non–ST-segment elevated acute coronary syndrome ultimately survived, while survival from CSI in those with structural heart disease was only 17%.

Microbiological findings were not a criterion for study inclusion, but Staphylococcus species accounted for 65% of the infections for which positive cultures were reported. Pseudomonas accounted for 13%. Less than 4% (3.8%) tested positive for multiple pathogens. A small proportion of patients had unusual infectious organisms.

As part of this analysis, the investigators developed an artificial intelligence model to predict CSI based on patient characteristics and other variables. However, the specificity of only around 70% led Dr. Ramakumar to conclude that it does not yet have practical value.

However, he believes that better methodology to detect CSI is needed, and he proposed a diagnostic algorithm that he believes would both improve detection rates and accelerate the time to diagnosis.
 

Algorithm proposed for detection of CSI

In this algorithm, the first step in symptomatic patients with a positive blood culture suspected of CSI is imaging, such as transthoracic echocardiography, to identify features of infective endocarditis or endarteritis. If the imaging is positive, further imaging, such as PET, that supports the diagnosis, should be adequate to support a diagnosis and treatment.

If initial imaging is negative, alternative diagnoses should be considered, but Dr. Ramakumar advised repeat imaging after 48 hours if symptoms persist and no other causes are found.

Dr. Ramakumar acknowledged the many limitations of this analysis, including the small sample size and the challenges of assembling coherent data from case reports with variable types of information submitted during different eras of PCI evolution. However, reiterating that CSI might be frequently missed, he emphasized that this problem might be bigger than currently understood.

It is difficult to rule out any possibility that CSI is frequently missed, but Andrew Sharp, MD, PhD, a consultant interventional cardiologist at the University Hospital of Wales, Cardiff, is skeptical.

“One might think this is a potential problem, but I cannot think of one patient in whom this has occurred,” Dr. Sharp said in an interview. He is fairly confident that they are extremely rare.

“When there is infection associated with a foreign body, such as a pacemaker, they do not typically resolve by themselves,” he explained. “Often the device has to be removed. If this was true for CSI, then I think we would be aware of these complications.”

However, he praised the investigators for taking a look at CSI in a systematic approach. An invited panelist during the CRT featured research, which is where these data were presented, Dr. Sharp was more interested in understanding why they do not occur now that data are available to suggest they are rare.

“Is there something in the coronary environment, such as the consistent blood flow, that protects against infection?” he asked. CSI is a valid area of further research, according to Dr. Sharp, but he does not consider infected stents to be a common threat based on his own sizable case series.

Dr. Ramakumar and Dr. Sharp reported no potential conflicts of interest.

Older adults who added a quarter mile of steps to their day showed a reduction in risk of cardiovascular events by 14% within 4 years, according to a study in more than 400 individuals.

“Aging is such a dynamic process, but most studies of daily steps and step goals are conducted on younger populations,” lead author Erin E. Dooley, PhD, an epidemiologist at the University of Alabama at Birmingham, said in an interview.

American Heart Association

The impact of more modest step goals in older adults has not been well studied, Dr. Dooley said.

The population in the current study ranged from 71 to 92 years, with an average age of 78 years. The older age and relatively short follow-up period show the importance of steps and physical activity in older adults, she said.

Dr. Dooley presented the study at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health meeting.

She and her colleagues analyzed a subsample of participants in Atherosclerosis Risk in Communities (ARIC) study, an ongoing study conducted by the National Heart, Lung, and Blood Institute. The study population included 452 adults for whom step data were available at visit 6 of the ARIC study between 2016 and 2017. Participants wore an accelerometer on the waist for at least 10 hours a day for at least 3 days. The mean age of the participants was 78.4 years, 59% were women, and 20% were Black.

Outcomes were measured through December 2019 and included fatal and nonfatal cardiovascular disease (CVD) events of coronary heart disease, stroke, and heart failure.

Overall, each additional 500 steps per day was linked to a 14% reduction in risk of a CVD event (hazard ratio, 0.86; 95% confidence interval, 0.76-0.98). The mean step count was 3,447 steps per day, and 34 participants (7.5%) experienced a CVD event over 1,269 person-years of follow-up.

The cumulative risk of CVD was significantly higher (11.5%) in the quartile of adults with the lowest step count (defined as fewer than 2,077 steps per day), compared with 3.5% in those with the highest step count (defined as at least 4,453 steps per day).

In addition, adults in the highest quartile of steps had a 77% reduced risk of a proximal CVD (within 3.5 years) event over the study period (HR, 0.23).

Kei Uesugi/Stone/Getty Images

Additional research is needed to explore whether increased steps prevent or delay CVD and whether low step counts may be a biomarker for underlying disease, the researchers noted in their abstract.

However, the results support the value of even a modest increase in activity to reduce CVD risk in older adults.

Small steps may get patients started

Dr. Dooley said she was surprised at the degree of benefits on heart health from 500 steps, and noted that the findings have clinical implications.

“Steps may be a more understandable metric for physical activity for patients than talking about moderate to vigorous intensity physical activity,” she said in an interview. “While we do not want to diminish the importance of higher intensity physical activity, encouraging small increases in the number of daily steps can also have great benefits for heart health.

“Steps are counted using a variety of devices and phones, so it may be helpful for patients to show clinicians their activity during well visits,” Dr. Dooley said. “Walking may also be more manageable for people as it is low impact. Achievable goals are also important. This study suggests that, for older adults, around 3,000 steps or more was associated with reduced CVD risk,” although the greatest benefits were seen with the most active group who averaged 4,500 or more steps per day.

More research is needed to show how steps may change over time, and how this relates to CVD and heart health,” she said. “At this time, we only had a single measure of physical activity.”

Study fills research gap for older adults

“Currently, the majority of the literature exploring a relationship between physical activity and the risk for developing cardiovascular disease has evaluated all adults together, not only those who are 70 year of age and older,” Monica C. Serra, PhD, of the University of Texas, San Antonio, said in an interview. “This study allows us to start to target specific cardiovascular recommendations for older adults.”.

“It is always exciting to see results from physical activity studies that continue to support prior evidence that even small amounts of physical activity are beneficial to cardiovascular health,” said Dr. Serra, who is also vice chair of the program committee for the meeting. “These results suggest that even if only small additions in physical activity are achievable, they may have cumulative benefits in reducing cardiovascular disease risk.” For clinicians, the results also provide targets that are easy for patients to understand, said Dr. Serra. Daily step counts allow clinicians to provide specific and measurable goals to help their older patients increase physical activity.

“Small additions in total daily step counts may have clinically meaningful benefits to heart health, so promoting their patients to make any slight changes that are able to be consistently incorporated into their schedule should be encouraged. This may be best monitored by encouraging the use of an activity tracker,” she said.

Although the current study adds to the literature with objective measures of physical activity utilizing accelerometers, these devices are not as sensitive at picking up activities such as bicycling or swimming, which may be more appropriate for some older adults with mobility limitations and chronic conditions, Dr. Serra said. Additional research is needed to assess the impact of other activities on CVD in the older population.

The meeting was sponsored by the American Heart Association. The study received no outside funding. Dr. Dooley and Dr. Serra had no financial conflicts to disclose.

Older adults who added a quarter mile of steps to their day showed a reduction in risk of cardiovascular events by 14% within 4 years, according to a study in more than 400 individuals.

“Aging is such a dynamic process, but most studies of daily steps and step goals are conducted on younger populations,” lead author Erin E. Dooley, PhD, an epidemiologist at the University of Alabama at Birmingham, said in an interview.

American Heart Association

The impact of more modest step goals in older adults has not been well studied, Dr. Dooley said.

The population in the current study ranged from 71 to 92 years, with an average age of 78 years. The older age and relatively short follow-up period show the importance of steps and physical activity in older adults, she said.

Dr. Dooley presented the study at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health meeting.

She and her colleagues analyzed a subsample of participants in Atherosclerosis Risk in Communities (ARIC) study, an ongoing study conducted by the National Heart, Lung, and Blood Institute. The study population included 452 adults for whom step data were available at visit 6 of the ARIC study between 2016 and 2017. Participants wore an accelerometer on the waist for at least 10 hours a day for at least 3 days. The mean age of the participants was 78.4 years, 59% were women, and 20% were Black.

Outcomes were measured through December 2019 and included fatal and nonfatal cardiovascular disease (CVD) events of coronary heart disease, stroke, and heart failure.

Overall, each additional 500 steps per day was linked to a 14% reduction in risk of a CVD event (hazard ratio, 0.86; 95% confidence interval, 0.76-0.98). The mean step count was 3,447 steps per day, and 34 participants (7.5%) experienced a CVD event over 1,269 person-years of follow-up.

The cumulative risk of CVD was significantly higher (11.5%) in the quartile of adults with the lowest step count (defined as fewer than 2,077 steps per day), compared with 3.5% in those with the highest step count (defined as at least 4,453 steps per day).

In addition, adults in the highest quartile of steps had a 77% reduced risk of a proximal CVD (within 3.5 years) event over the study period (HR, 0.23).

Kei Uesugi/Stone/Getty Images

Additional research is needed to explore whether increased steps prevent or delay CVD and whether low step counts may be a biomarker for underlying disease, the researchers noted in their abstract.

However, the results support the value of even a modest increase in activity to reduce CVD risk in older adults.

Small steps may get patients started

Dr. Dooley said she was surprised at the degree of benefits on heart health from 500 steps, and noted that the findings have clinical implications.

“Steps may be a more understandable metric for physical activity for patients than talking about moderate to vigorous intensity physical activity,” she said in an interview. “While we do not want to diminish the importance of higher intensity physical activity, encouraging small increases in the number of daily steps can also have great benefits for heart health.

“Steps are counted using a variety of devices and phones, so it may be helpful for patients to show clinicians their activity during well visits,” Dr. Dooley said. “Walking may also be more manageable for people as it is low impact. Achievable goals are also important. This study suggests that, for older adults, around 3,000 steps or more was associated with reduced CVD risk,” although the greatest benefits were seen with the most active group who averaged 4,500 or more steps per day.

More research is needed to show how steps may change over time, and how this relates to CVD and heart health,” she said. “At this time, we only had a single measure of physical activity.”

Study fills research gap for older adults

“Currently, the majority of the literature exploring a relationship between physical activity and the risk for developing cardiovascular disease has evaluated all adults together, not only those who are 70 year of age and older,” Monica C. Serra, PhD, of the University of Texas, San Antonio, said in an interview. “This study allows us to start to target specific cardiovascular recommendations for older adults.”.

“It is always exciting to see results from physical activity studies that continue to support prior evidence that even small amounts of physical activity are beneficial to cardiovascular health,” said Dr. Serra, who is also vice chair of the program committee for the meeting. “These results suggest that even if only small additions in physical activity are achievable, they may have cumulative benefits in reducing cardiovascular disease risk.” For clinicians, the results also provide targets that are easy for patients to understand, said Dr. Serra. Daily step counts allow clinicians to provide specific and measurable goals to help their older patients increase physical activity.

“Small additions in total daily step counts may have clinically meaningful benefits to heart health, so promoting their patients to make any slight changes that are able to be consistently incorporated into their schedule should be encouraged. This may be best monitored by encouraging the use of an activity tracker,” she said.

Although the current study adds to the literature with objective measures of physical activity utilizing accelerometers, these devices are not as sensitive at picking up activities such as bicycling or swimming, which may be more appropriate for some older adults with mobility limitations and chronic conditions, Dr. Serra said. Additional research is needed to assess the impact of other activities on CVD in the older population.

The meeting was sponsored by the American Heart Association. The study received no outside funding. Dr. Dooley and Dr. Serra had no financial conflicts to disclose.

Older adults who added a quarter mile of steps to their day showed a reduction in risk of cardiovascular events by 14% within 4 years, according to a study in more than 400 individuals.

“Aging is such a dynamic process, but most studies of daily steps and step goals are conducted on younger populations,” lead author Erin E. Dooley, PhD, an epidemiologist at the University of Alabama at Birmingham, said in an interview.

American Heart Association

The impact of more modest step goals in older adults has not been well studied, Dr. Dooley said.

The population in the current study ranged from 71 to 92 years, with an average age of 78 years. The older age and relatively short follow-up period show the importance of steps and physical activity in older adults, she said.

Dr. Dooley presented the study at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health meeting.

She and her colleagues analyzed a subsample of participants in Atherosclerosis Risk in Communities (ARIC) study, an ongoing study conducted by the National Heart, Lung, and Blood Institute. The study population included 452 adults for whom step data were available at visit 6 of the ARIC study between 2016 and 2017. Participants wore an accelerometer on the waist for at least 10 hours a day for at least 3 days. The mean age of the participants was 78.4 years, 59% were women, and 20% were Black.

Outcomes were measured through December 2019 and included fatal and nonfatal cardiovascular disease (CVD) events of coronary heart disease, stroke, and heart failure.

Overall, each additional 500 steps per day was linked to a 14% reduction in risk of a CVD event (hazard ratio, 0.86; 95% confidence interval, 0.76-0.98). The mean step count was 3,447 steps per day, and 34 participants (7.5%) experienced a CVD event over 1,269 person-years of follow-up.

The cumulative risk of CVD was significantly higher (11.5%) in the quartile of adults with the lowest step count (defined as fewer than 2,077 steps per day), compared with 3.5% in those with the highest step count (defined as at least 4,453 steps per day).

In addition, adults in the highest quartile of steps had a 77% reduced risk of a proximal CVD (within 3.5 years) event over the study period (HR, 0.23).

Kei Uesugi/Stone/Getty Images

Additional research is needed to explore whether increased steps prevent or delay CVD and whether low step counts may be a biomarker for underlying disease, the researchers noted in their abstract.

However, the results support the value of even a modest increase in activity to reduce CVD risk in older adults.

Small steps may get patients started

Dr. Dooley said she was surprised at the degree of benefits on heart health from 500 steps, and noted that the findings have clinical implications.

“Steps may be a more understandable metric for physical activity for patients than talking about moderate to vigorous intensity physical activity,” she said in an interview. “While we do not want to diminish the importance of higher intensity physical activity, encouraging small increases in the number of daily steps can also have great benefits for heart health.

“Steps are counted using a variety of devices and phones, so it may be helpful for patients to show clinicians their activity during well visits,” Dr. Dooley said. “Walking may also be more manageable for people as it is low impact. Achievable goals are also important. This study suggests that, for older adults, around 3,000 steps or more was associated with reduced CVD risk,” although the greatest benefits were seen with the most active group who averaged 4,500 or more steps per day.

More research is needed to show how steps may change over time, and how this relates to CVD and heart health,” she said. “At this time, we only had a single measure of physical activity.”

Study fills research gap for older adults

“Currently, the majority of the literature exploring a relationship between physical activity and the risk for developing cardiovascular disease has evaluated all adults together, not only those who are 70 year of age and older,” Monica C. Serra, PhD, of the University of Texas, San Antonio, said in an interview. “This study allows us to start to target specific cardiovascular recommendations for older adults.”.

“It is always exciting to see results from physical activity studies that continue to support prior evidence that even small amounts of physical activity are beneficial to cardiovascular health,” said Dr. Serra, who is also vice chair of the program committee for the meeting. “These results suggest that even if only small additions in physical activity are achievable, they may have cumulative benefits in reducing cardiovascular disease risk.” For clinicians, the results also provide targets that are easy for patients to understand, said Dr. Serra. Daily step counts allow clinicians to provide specific and measurable goals to help their older patients increase physical activity.

“Small additions in total daily step counts may have clinically meaningful benefits to heart health, so promoting their patients to make any slight changes that are able to be consistently incorporated into their schedule should be encouraged. This may be best monitored by encouraging the use of an activity tracker,” she said.

Although the current study adds to the literature with objective measures of physical activity utilizing accelerometers, these devices are not as sensitive at picking up activities such as bicycling or swimming, which may be more appropriate for some older adults with mobility limitations and chronic conditions, Dr. Serra said. Additional research is needed to assess the impact of other activities on CVD in the older population.

The meeting was sponsored by the American Heart Association. The study received no outside funding. Dr. Dooley and Dr. Serra had no financial conflicts to disclose.

Insomnia – difficulty falling or staying asleep – was associated with a 69% greater risk of having a myocardial infarction than among adults without insomnia, according to new research.

Those who slept 5 or fewer hours per night had the highest risk for MI, and those with both diabetes and insomnia had double the risk for MI, compared with patients without these comorbidities.

amenic181/Getty Images

The findings are from a meta-analysis of studies in more than 1 million patients, almost all without prior MI who were, on average, in their early 50s and followed for 9 years.

Yomna E. Dean, a medical student at Alexandria (Egypt) University, reported these results in a press briefing, and the study was simultaneously published in Clinical Cardiology. It will be presented at the upcoming at the annual scientific sessions of the American College of Cardiology.

“Insomnia and ]at least] 5 hours of sleep are highly associated with increased incidence of MI, an association comparable to that of other MI risk factors and as such, it should be considered as a risk factor for MI and to be incorporated into MI prevention guidelines,” the researchers concluded.

“We believe that [insomnia] should be screened and patients should be educated about the importance of sleep because nowadays insomnia is no longer a disease – sleep deprivation could also be a life choice,” Ms, Dean told a press conference prior to the meeting.

“Clinicians must educate the patients about the importance of sleep in maintaining a healthy heart and encourage proper sleep hygiene,” Ms. Dean reiterated in an email. “And if a patient still has insomnia, other methods should be considered such as cognitive-behavior[al] therapy for insomnia [CBT-I].”
 

Adds to growing evidence

This study does not allow any conclusion about whether treating insomnia will reduce heart attack risk, Jennifer L. Martin, PhD, president of the American Academy of Sleep Medicine, noted in a comment. Nor does it report the diversity of study participants, since insomnia is also a health equity issue, she noted, and insomnia symptoms and comorbidities were self-reported.

However, this analysis “adds to the growing evidence that poor quality or insufficient sleep is associated with poor health,” said Dr. Martin, professor of medicine at the University of California, Los Angeles, who was not involved with this research.

The study reinforces the recommendation from the American Heart Association, which includes “Get Healthy Sleep” as one of “Life’s Essential 8” for heart health, Dr. Martin noted.

“Particularly in primary care where disease prevention and health promotion are important, clinicians should be asking all patients about their sleep – just like they ask about diet and exercise – as a key aspect of maintaining heart health,” she said.

Advice about basic sleep hygiene advice is a first step, she noted.

When improved sleep hygiene is not enough to address chronic insomnia, the AASM’s clinical practice guidelines and the guidelines of the Department of Veterans Affairs/Department of Defense, recommend first-line treatment with CBT-I, typically offered by a sleep specialist or mental health clinician.

Similarly, the American College of Physicians suggests that sleeping pills should be reserved for short-term use in patients who may not benefit sufficiently from CBT-I.
 

Sleeping too little, too much, equally harmful

“Studies have found that insomnia and subsequent sleep deprivation puts the body under stress,” Ms. Dean said. “This triggers cortisol release which could accelerate atherosclerosis,” and increase risk of MI.

For this analysis, the researchers identified nine observational studies, published from 1998 to 2019, with data on incident MI in adults who had insomnia.

The diagnosis of insomnia was based on ICD diagnostic codes or on the DSM‐5, which defines insomnia as the presence of any of the following three symptoms: difficulty initiating sleep, difficulty maintaining sleep, or early morning awakening with inability to return to sleep. Patients with sleep apnea were excluded.

The studies were in populations in China, Germany, Norway, Taiwan, United Kingdom, and United States, in 1.1 million adults aged 18 and older. The patients had a mean age of 52 years and 13% had insomnia.

During follow-up, 2,406 of 153,881 patients with insomnia, and 12,398 of 1,030,375 patients without insomnia had an MI.

In the pooled analysis, patients with insomnia had a significantly increased risk of MI (relative risk, 1.69; P < .00001), after adjusting for age, gender, diabetes, hypertension, high cholesterol, and smoking.

Sleeping 5 hours or less was associated with a greater risk for MI than sleeping 6 hours, or 7-8 hours, but sleeping 9 hours or more was just as harmful.

Patients who had difficulty initiating and maintaining sleep – two symptoms of insomnia – had a 13% increased risk for MI compared with other patients (RR, 1.13; P = .003).

However, patients who had nonrestorative sleep and daytime dysfunction despite adequate sleep – which is common – did not have an increased risk of MI, compared with other patients (RR, 1.06; P = .46).

Women with insomnia had a 2.24-fold greater risk for MI than other women, whereas men with insomnia had a 2.03-fold greater risk for MI than other men.

Patients with insomnia had a greater risk for MI than those without insomnia in subgroups based on patients’ age (< 65 and > 65), follow up duration (≤ 5 years and > 5 years), and comorbidities (diabetes, hypertension, and hyperlipidemia).

The authors reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Insomnia – difficulty falling or staying asleep – was associated with a 69% greater risk of having a myocardial infarction than among adults without insomnia, according to new research.

Those who slept 5 or fewer hours per night had the highest risk for MI, and those with both diabetes and insomnia had double the risk for MI, compared with patients without these comorbidities.

amenic181/Getty Images

The findings are from a meta-analysis of studies in more than 1 million patients, almost all without prior MI who were, on average, in their early 50s and followed for 9 years.

Yomna E. Dean, a medical student at Alexandria (Egypt) University, reported these results in a press briefing, and the study was simultaneously published in Clinical Cardiology. It will be presented at the upcoming at the annual scientific sessions of the American College of Cardiology.

“Insomnia and ]at least] 5 hours of sleep are highly associated with increased incidence of MI, an association comparable to that of other MI risk factors and as such, it should be considered as a risk factor for MI and to be incorporated into MI prevention guidelines,” the researchers concluded.

“We believe that [insomnia] should be screened and patients should be educated about the importance of sleep because nowadays insomnia is no longer a disease – sleep deprivation could also be a life choice,” Ms, Dean told a press conference prior to the meeting.

“Clinicians must educate the patients about the importance of sleep in maintaining a healthy heart and encourage proper sleep hygiene,” Ms. Dean reiterated in an email. “And if a patient still has insomnia, other methods should be considered such as cognitive-behavior[al] therapy for insomnia [CBT-I].”
 

Adds to growing evidence

This study does not allow any conclusion about whether treating insomnia will reduce heart attack risk, Jennifer L. Martin, PhD, president of the American Academy of Sleep Medicine, noted in a comment. Nor does it report the diversity of study participants, since insomnia is also a health equity issue, she noted, and insomnia symptoms and comorbidities were self-reported.

However, this analysis “adds to the growing evidence that poor quality or insufficient sleep is associated with poor health,” said Dr. Martin, professor of medicine at the University of California, Los Angeles, who was not involved with this research.

The study reinforces the recommendation from the American Heart Association, which includes “Get Healthy Sleep” as one of “Life’s Essential 8” for heart health, Dr. Martin noted.

“Particularly in primary care where disease prevention and health promotion are important, clinicians should be asking all patients about their sleep – just like they ask about diet and exercise – as a key aspect of maintaining heart health,” she said.

Advice about basic sleep hygiene advice is a first step, she noted.

When improved sleep hygiene is not enough to address chronic insomnia, the AASM’s clinical practice guidelines and the guidelines of the Department of Veterans Affairs/Department of Defense, recommend first-line treatment with CBT-I, typically offered by a sleep specialist or mental health clinician.

Similarly, the American College of Physicians suggests that sleeping pills should be reserved for short-term use in patients who may not benefit sufficiently from CBT-I.
 

Sleeping too little, too much, equally harmful

“Studies have found that insomnia and subsequent sleep deprivation puts the body under stress,” Ms. Dean said. “This triggers cortisol release which could accelerate atherosclerosis,” and increase risk of MI.

For this analysis, the researchers identified nine observational studies, published from 1998 to 2019, with data on incident MI in adults who had insomnia.

The diagnosis of insomnia was based on ICD diagnostic codes or on the DSM‐5, which defines insomnia as the presence of any of the following three symptoms: difficulty initiating sleep, difficulty maintaining sleep, or early morning awakening with inability to return to sleep. Patients with sleep apnea were excluded.

The studies were in populations in China, Germany, Norway, Taiwan, United Kingdom, and United States, in 1.1 million adults aged 18 and older. The patients had a mean age of 52 years and 13% had insomnia.

During follow-up, 2,406 of 153,881 patients with insomnia, and 12,398 of 1,030,375 patients without insomnia had an MI.

In the pooled analysis, patients with insomnia had a significantly increased risk of MI (relative risk, 1.69; P < .00001), after adjusting for age, gender, diabetes, hypertension, high cholesterol, and smoking.

Sleeping 5 hours or less was associated with a greater risk for MI than sleeping 6 hours, or 7-8 hours, but sleeping 9 hours or more was just as harmful.

Patients who had difficulty initiating and maintaining sleep – two symptoms of insomnia – had a 13% increased risk for MI compared with other patients (RR, 1.13; P = .003).

However, patients who had nonrestorative sleep and daytime dysfunction despite adequate sleep – which is common – did not have an increased risk of MI, compared with other patients (RR, 1.06; P = .46).

Women with insomnia had a 2.24-fold greater risk for MI than other women, whereas men with insomnia had a 2.03-fold greater risk for MI than other men.

Patients with insomnia had a greater risk for MI than those without insomnia in subgroups based on patients’ age (< 65 and > 65), follow up duration (≤ 5 years and > 5 years), and comorbidities (diabetes, hypertension, and hyperlipidemia).

The authors reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Insomnia – difficulty falling or staying asleep – was associated with a 69% greater risk of having a myocardial infarction than among adults without insomnia, according to new research.

Those who slept 5 or fewer hours per night had the highest risk for MI, and those with both diabetes and insomnia had double the risk for MI, compared with patients without these comorbidities.

amenic181/Getty Images

The findings are from a meta-analysis of studies in more than 1 million patients, almost all without prior MI who were, on average, in their early 50s and followed for 9 years.

Yomna E. Dean, a medical student at Alexandria (Egypt) University, reported these results in a press briefing, and the study was simultaneously published in Clinical Cardiology. It will be presented at the upcoming at the annual scientific sessions of the American College of Cardiology.

“Insomnia and ]at least] 5 hours of sleep are highly associated with increased incidence of MI, an association comparable to that of other MI risk factors and as such, it should be considered as a risk factor for MI and to be incorporated into MI prevention guidelines,” the researchers concluded.

“We believe that [insomnia] should be screened and patients should be educated about the importance of sleep because nowadays insomnia is no longer a disease – sleep deprivation could also be a life choice,” Ms, Dean told a press conference prior to the meeting.

“Clinicians must educate the patients about the importance of sleep in maintaining a healthy heart and encourage proper sleep hygiene,” Ms. Dean reiterated in an email. “And if a patient still has insomnia, other methods should be considered such as cognitive-behavior[al] therapy for insomnia [CBT-I].”
 

Adds to growing evidence

This study does not allow any conclusion about whether treating insomnia will reduce heart attack risk, Jennifer L. Martin, PhD, president of the American Academy of Sleep Medicine, noted in a comment. Nor does it report the diversity of study participants, since insomnia is also a health equity issue, she noted, and insomnia symptoms and comorbidities were self-reported.

However, this analysis “adds to the growing evidence that poor quality or insufficient sleep is associated with poor health,” said Dr. Martin, professor of medicine at the University of California, Los Angeles, who was not involved with this research.

The study reinforces the recommendation from the American Heart Association, which includes “Get Healthy Sleep” as one of “Life’s Essential 8” for heart health, Dr. Martin noted.

“Particularly in primary care where disease prevention and health promotion are important, clinicians should be asking all patients about their sleep – just like they ask about diet and exercise – as a key aspect of maintaining heart health,” she said.

Advice about basic sleep hygiene advice is a first step, she noted.

When improved sleep hygiene is not enough to address chronic insomnia, the AASM’s clinical practice guidelines and the guidelines of the Department of Veterans Affairs/Department of Defense, recommend first-line treatment with CBT-I, typically offered by a sleep specialist or mental health clinician.

Similarly, the American College of Physicians suggests that sleeping pills should be reserved for short-term use in patients who may not benefit sufficiently from CBT-I.
 

Sleeping too little, too much, equally harmful

“Studies have found that insomnia and subsequent sleep deprivation puts the body under stress,” Ms. Dean said. “This triggers cortisol release which could accelerate atherosclerosis,” and increase risk of MI.

For this analysis, the researchers identified nine observational studies, published from 1998 to 2019, with data on incident MI in adults who had insomnia.

The diagnosis of insomnia was based on ICD diagnostic codes or on the DSM‐5, which defines insomnia as the presence of any of the following three symptoms: difficulty initiating sleep, difficulty maintaining sleep, or early morning awakening with inability to return to sleep. Patients with sleep apnea were excluded.

The studies were in populations in China, Germany, Norway, Taiwan, United Kingdom, and United States, in 1.1 million adults aged 18 and older. The patients had a mean age of 52 years and 13% had insomnia.

During follow-up, 2,406 of 153,881 patients with insomnia, and 12,398 of 1,030,375 patients without insomnia had an MI.

In the pooled analysis, patients with insomnia had a significantly increased risk of MI (relative risk, 1.69; P < .00001), after adjusting for age, gender, diabetes, hypertension, high cholesterol, and smoking.

Sleeping 5 hours or less was associated with a greater risk for MI than sleeping 6 hours, or 7-8 hours, but sleeping 9 hours or more was just as harmful.

Patients who had difficulty initiating and maintaining sleep – two symptoms of insomnia – had a 13% increased risk for MI compared with other patients (RR, 1.13; P = .003).

However, patients who had nonrestorative sleep and daytime dysfunction despite adequate sleep – which is common – did not have an increased risk of MI, compared with other patients (RR, 1.06; P = .46).

Women with insomnia had a 2.24-fold greater risk for MI than other women, whereas men with insomnia had a 2.03-fold greater risk for MI than other men.

Patients with insomnia had a greater risk for MI than those without insomnia in subgroups based on patients’ age (< 65 and > 65), follow up duration (≤ 5 years and > 5 years), and comorbidities (diabetes, hypertension, and hyperlipidemia).

The authors reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A multipart study reports that erythritol – a sugar alcohol (polyol) increasingly used as an artificial sweetener that is also made in the body – is associated with risk of major adverse cardiovascular events (MACE) and promotes clotting (thrombosis).

Erythritol is one of the most widely used artificial sweeteners with rapidly increasing prevalence in processed and “keto-related” foods. Artificial sweeteners are “generally recognized as safe” (GRAS) by the U.S. Food and Drug Administration, so there is no requirement for long-term safety studies, and little is known about the long-term health effects.

The current research, published online in Nature Medicine by Marco Witkowski, MD, of the Lerner Research Institute at Cleveland Clinic and colleagues, had multiple parts.

First, in a group of patients undergoing cardiac risk assessment, the researchers found that high levels of polyols, especially erythritol, were associated with increased 3-year risk of MACE, defined as cardiovascular death or nonfatal myocardial infarction or stroke. 

Next, the association of erythritol with this outcome was reproduced in two large U.S. and European groups of stable patients undergoing elective cardiac evaluation.

Next, adding erythritol to whole blood or platelets led to clot activation. And lastly, in eight healthy volunteers, ingesting 30 g of an erythritol-sweetened drink – comparable to a single can of commercially available beverage or a pint of keto ice cream – induced marked and sustained (> 2 day) increases in levels of plasma erythritol.

“Our study shows that when participants consumed an artificially sweetened beverage with an amount of erythritol found in many processed foods, markedly elevated levels in the blood are observed for days – levels well above those observed to enhance clotting risks,” said senior author Stanley L. Hazen, MD, PhD.  

“It is important that further safety studies are conducted to examine the long-term effects of artificial sweeteners in general, and erythritol specifically, on risks for heart attack and stroke, particularly in people at higher risk for cardiovascular disease,” Dr. Hazen, co–section head of preventive cardiology at Cleveland Clinic, said in a press release from his institution.

“Sweeteners like erythritol have rapidly increased in popularity in recent years, but there needs to be more in-depth research into their long-term effects. Cardiovascular disease builds over time, and heart disease is the leading cause of death globally. We need to make sure the foods we eat aren’t hidden contributors,” Dr. Hazen urged.

The topic remains controversial.

Duane Mellor, PhD, a registered dietitian and senior teaching fellow at Aston University, Birmingham, England, told the U.K. Science Media Centre: “This paper effectively shows multiple pieces of a jigsaw exploring the effects of erythritol – although it claims to show an associated risk with the use of erythritol as an artificial sweetener and cardiovascular disease, I believe it fails to do so, as ultimately, erythritol can be made inside our bodies and the intake in most people’s diet is much lower than the amount given in this study.” 

Dr. Hazen countered that data from the 2013-2014 National Health and Nutrition Examination Survey (NHANES) in the United States show that, in some individuals, daily intake of erythritol is estimated to reach 30 g/day. 

“Many try and reduce sugar intake by taking many teaspoons of erythritol in their tea, coffee, etc., instead of sugar,” Dr. Hazen added. “Or they eat keto processed foods that have significant quantities of erythritol within it.”

“These studies are a warning for how our processed food (keto and zero sugar, especially) may inadvertently be causing risk/harm. … in the very subset of subjects who are most vulnerable,” according to Dr. Hazen.
 

Erythritol marketed as ‘zero calorie’, ‘non-nutritive’, or ‘natural’

Patients with type 2 diabetes and obesity are often advised to replace sugar with artificial sweeteners for better glucose control and weight loss, but growing epidemiologic evidence links artificial sweetener consumption with weight gain, insulin resistance, type 2 diabetes, and cardiovascular disease, the researchers write.

Erythritol is naturally present in low amounts in fruits and vegetables; the artificial sweetener erythritol that is produced from corn is only 70% as sweet as sugar.

Upon ingestion it is poorly metabolized, and most is excreted in the urine, so it is characterized as a “zero-calorie,” “non-nutritive,” or “natural sweetener.” It is predicted to double in marketshare in the sweetener sector in the next 5 years.
 

Multipart study

In the first part of their study, in a discovery cohort in 1,157 patients undergoing cardiovascular assessment with 3-year outcomes, the researchers identified polyols that were associated with MACE, and erythritol was among the top MACE-associated molecules.

Next, in a U.S. validation cohort of 2,149 patients, over a 3-year follow-up, patients with plasma levels of erythritol in the highest quartile had a 1.8-fold higher risk of MACE than patients in the lowest quartile (P = .007), after adjusting for cardiovascular risk factors.

In a European validation cohort of 833 patients, over a 3-year follow-up, patients with plasma levels of erythritol in the highest quartile had a 2.21-fold higher risk of MACE than patients in the lowest quartile (P = .010, after adjustment).

At physiologic levels, erythritol enhanced platelet reactivity in vitro and thrombosis formation in vivo.

Finally, in a prospective pilot intervention study, erythritol ingestion in healthy volunteers induced marked and sustained increases in plasma erythritol levels well above thresholds associated with heightened platelet reactivity and thrombosis potential in in vitro and in vivo studies.
 

Others weigh in

“While I think the finding certainly warrants further investigation, don’t throw out your sweeteners just yet,” commented Oliver Jones, PhD, professor of chemistry at the Royal Melbourne Institute of Technology.

“This study only looks at erythritol, and artificial sweeteners are generally considered safe. Any possible (and, as yet unproven) risks of excess erythritol would also need to be balanced against the very real health risks of excess glucose consumption,” he said.

Dr. Hazen responded: “True enough. Erythritol is but one of many artificial sweeteners. That is why it is important to read labels. This study can make patients be informed about how to potentially avoid something that might cause them inadvertent harm.”

“The key findings of this study are that high blood levels of erythritol are strongly associated with cardiovascular outcomes in high-risk patients, which has been replicated in separate validation studies,” said Tom Sanders, DSc, PhD, professor emeritus of nutrition and dietetics, King’s College London.

“Diabetes UK currently advises diabetes patients not to use polyols,” he added.

Dr. Hazen noted that “About three-quarters of the participants had coronary disease, high blood pressure, and about a fifth had diabetes.”

The researchers acknowledge, however, that the observational studies cannot show cause and effect.

The study was supported by the Office of Dietary Supplements at the National Institutes of Health, the Leducq Foundation, and the German Research Foundation (Deutsche Forschungsgemeinschaft). Dr. Mellor, Dr. Jones, and Dr. Sanders have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A multipart study reports that erythritol – a sugar alcohol (polyol) increasingly used as an artificial sweetener that is also made in the body – is associated with risk of major adverse cardiovascular events (MACE) and promotes clotting (thrombosis).

Erythritol is one of the most widely used artificial sweeteners with rapidly increasing prevalence in processed and “keto-related” foods. Artificial sweeteners are “generally recognized as safe” (GRAS) by the U.S. Food and Drug Administration, so there is no requirement for long-term safety studies, and little is known about the long-term health effects.

The current research, published online in Nature Medicine by Marco Witkowski, MD, of the Lerner Research Institute at Cleveland Clinic and colleagues, had multiple parts.

First, in a group of patients undergoing cardiac risk assessment, the researchers found that high levels of polyols, especially erythritol, were associated with increased 3-year risk of MACE, defined as cardiovascular death or nonfatal myocardial infarction or stroke. 

Next, the association of erythritol with this outcome was reproduced in two large U.S. and European groups of stable patients undergoing elective cardiac evaluation.

Next, adding erythritol to whole blood or platelets led to clot activation. And lastly, in eight healthy volunteers, ingesting 30 g of an erythritol-sweetened drink – comparable to a single can of commercially available beverage or a pint of keto ice cream – induced marked and sustained (> 2 day) increases in levels of plasma erythritol.

“Our study shows that when participants consumed an artificially sweetened beverage with an amount of erythritol found in many processed foods, markedly elevated levels in the blood are observed for days – levels well above those observed to enhance clotting risks,” said senior author Stanley L. Hazen, MD, PhD.  

“It is important that further safety studies are conducted to examine the long-term effects of artificial sweeteners in general, and erythritol specifically, on risks for heart attack and stroke, particularly in people at higher risk for cardiovascular disease,” Dr. Hazen, co–section head of preventive cardiology at Cleveland Clinic, said in a press release from his institution.

“Sweeteners like erythritol have rapidly increased in popularity in recent years, but there needs to be more in-depth research into their long-term effects. Cardiovascular disease builds over time, and heart disease is the leading cause of death globally. We need to make sure the foods we eat aren’t hidden contributors,” Dr. Hazen urged.

The topic remains controversial.

Duane Mellor, PhD, a registered dietitian and senior teaching fellow at Aston University, Birmingham, England, told the U.K. Science Media Centre: “This paper effectively shows multiple pieces of a jigsaw exploring the effects of erythritol – although it claims to show an associated risk with the use of erythritol as an artificial sweetener and cardiovascular disease, I believe it fails to do so, as ultimately, erythritol can be made inside our bodies and the intake in most people’s diet is much lower than the amount given in this study.” 

Dr. Hazen countered that data from the 2013-2014 National Health and Nutrition Examination Survey (NHANES) in the United States show that, in some individuals, daily intake of erythritol is estimated to reach 30 g/day. 

“Many try and reduce sugar intake by taking many teaspoons of erythritol in their tea, coffee, etc., instead of sugar,” Dr. Hazen added. “Or they eat keto processed foods that have significant quantities of erythritol within it.”

“These studies are a warning for how our processed food (keto and zero sugar, especially) may inadvertently be causing risk/harm. … in the very subset of subjects who are most vulnerable,” according to Dr. Hazen.
 

Erythritol marketed as ‘zero calorie’, ‘non-nutritive’, or ‘natural’

Patients with type 2 diabetes and obesity are often advised to replace sugar with artificial sweeteners for better glucose control and weight loss, but growing epidemiologic evidence links artificial sweetener consumption with weight gain, insulin resistance, type 2 diabetes, and cardiovascular disease, the researchers write.

Erythritol is naturally present in low amounts in fruits and vegetables; the artificial sweetener erythritol that is produced from corn is only 70% as sweet as sugar.

Upon ingestion it is poorly metabolized, and most is excreted in the urine, so it is characterized as a “zero-calorie,” “non-nutritive,” or “natural sweetener.” It is predicted to double in marketshare in the sweetener sector in the next 5 years.
 

Multipart study

In the first part of their study, in a discovery cohort in 1,157 patients undergoing cardiovascular assessment with 3-year outcomes, the researchers identified polyols that were associated with MACE, and erythritol was among the top MACE-associated molecules.

Next, in a U.S. validation cohort of 2,149 patients, over a 3-year follow-up, patients with plasma levels of erythritol in the highest quartile had a 1.8-fold higher risk of MACE than patients in the lowest quartile (P = .007), after adjusting for cardiovascular risk factors.

In a European validation cohort of 833 patients, over a 3-year follow-up, patients with plasma levels of erythritol in the highest quartile had a 2.21-fold higher risk of MACE than patients in the lowest quartile (P = .010, after adjustment).

At physiologic levels, erythritol enhanced platelet reactivity in vitro and thrombosis formation in vivo.

Finally, in a prospective pilot intervention study, erythritol ingestion in healthy volunteers induced marked and sustained increases in plasma erythritol levels well above thresholds associated with heightened platelet reactivity and thrombosis potential in in vitro and in vivo studies.
 

Others weigh in

“While I think the finding certainly warrants further investigation, don’t throw out your sweeteners just yet,” commented Oliver Jones, PhD, professor of chemistry at the Royal Melbourne Institute of Technology.

“This study only looks at erythritol, and artificial sweeteners are generally considered safe. Any possible (and, as yet unproven) risks of excess erythritol would also need to be balanced against the very real health risks of excess glucose consumption,” he said.

Dr. Hazen responded: “True enough. Erythritol is but one of many artificial sweeteners. That is why it is important to read labels. This study can make patients be informed about how to potentially avoid something that might cause them inadvertent harm.”

“The key findings of this study are that high blood levels of erythritol are strongly associated with cardiovascular outcomes in high-risk patients, which has been replicated in separate validation studies,” said Tom Sanders, DSc, PhD, professor emeritus of nutrition and dietetics, King’s College London.

“Diabetes UK currently advises diabetes patients not to use polyols,” he added.

Dr. Hazen noted that “About three-quarters of the participants had coronary disease, high blood pressure, and about a fifth had diabetes.”

The researchers acknowledge, however, that the observational studies cannot show cause and effect.

The study was supported by the Office of Dietary Supplements at the National Institutes of Health, the Leducq Foundation, and the German Research Foundation (Deutsche Forschungsgemeinschaft). Dr. Mellor, Dr. Jones, and Dr. Sanders have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A multipart study reports that erythritol – a sugar alcohol (polyol) increasingly used as an artificial sweetener that is also made in the body – is associated with risk of major adverse cardiovascular events (MACE) and promotes clotting (thrombosis).

Erythritol is one of the most widely used artificial sweeteners with rapidly increasing prevalence in processed and “keto-related” foods. Artificial sweeteners are “generally recognized as safe” (GRAS) by the U.S. Food and Drug Administration, so there is no requirement for long-term safety studies, and little is known about the long-term health effects.

The current research, published online in Nature Medicine by Marco Witkowski, MD, of the Lerner Research Institute at Cleveland Clinic and colleagues, had multiple parts.

First, in a group of patients undergoing cardiac risk assessment, the researchers found that high levels of polyols, especially erythritol, were associated with increased 3-year risk of MACE, defined as cardiovascular death or nonfatal myocardial infarction or stroke. 

Next, the association of erythritol with this outcome was reproduced in two large U.S. and European groups of stable patients undergoing elective cardiac evaluation.

Next, adding erythritol to whole blood or platelets led to clot activation. And lastly, in eight healthy volunteers, ingesting 30 g of an erythritol-sweetened drink – comparable to a single can of commercially available beverage or a pint of keto ice cream – induced marked and sustained (> 2 day) increases in levels of plasma erythritol.

“Our study shows that when participants consumed an artificially sweetened beverage with an amount of erythritol found in many processed foods, markedly elevated levels in the blood are observed for days – levels well above those observed to enhance clotting risks,” said senior author Stanley L. Hazen, MD, PhD.  

“It is important that further safety studies are conducted to examine the long-term effects of artificial sweeteners in general, and erythritol specifically, on risks for heart attack and stroke, particularly in people at higher risk for cardiovascular disease,” Dr. Hazen, co–section head of preventive cardiology at Cleveland Clinic, said in a press release from his institution.

“Sweeteners like erythritol have rapidly increased in popularity in recent years, but there needs to be more in-depth research into their long-term effects. Cardiovascular disease builds over time, and heart disease is the leading cause of death globally. We need to make sure the foods we eat aren’t hidden contributors,” Dr. Hazen urged.

The topic remains controversial.

Duane Mellor, PhD, a registered dietitian and senior teaching fellow at Aston University, Birmingham, England, told the U.K. Science Media Centre: “This paper effectively shows multiple pieces of a jigsaw exploring the effects of erythritol – although it claims to show an associated risk with the use of erythritol as an artificial sweetener and cardiovascular disease, I believe it fails to do so, as ultimately, erythritol can be made inside our bodies and the intake in most people’s diet is much lower than the amount given in this study.” 

Dr. Hazen countered that data from the 2013-2014 National Health and Nutrition Examination Survey (NHANES) in the United States show that, in some individuals, daily intake of erythritol is estimated to reach 30 g/day. 

“Many try and reduce sugar intake by taking many teaspoons of erythritol in their tea, coffee, etc., instead of sugar,” Dr. Hazen added. “Or they eat keto processed foods that have significant quantities of erythritol within it.”

“These studies are a warning for how our processed food (keto and zero sugar, especially) may inadvertently be causing risk/harm. … in the very subset of subjects who are most vulnerable,” according to Dr. Hazen.
 

Erythritol marketed as ‘zero calorie’, ‘non-nutritive’, or ‘natural’

Patients with type 2 diabetes and obesity are often advised to replace sugar with artificial sweeteners for better glucose control and weight loss, but growing epidemiologic evidence links artificial sweetener consumption with weight gain, insulin resistance, type 2 diabetes, and cardiovascular disease, the researchers write.

Erythritol is naturally present in low amounts in fruits and vegetables; the artificial sweetener erythritol that is produced from corn is only 70% as sweet as sugar.

Upon ingestion it is poorly metabolized, and most is excreted in the urine, so it is characterized as a “zero-calorie,” “non-nutritive,” or “natural sweetener.” It is predicted to double in marketshare in the sweetener sector in the next 5 years.
 

Multipart study

In the first part of their study, in a discovery cohort in 1,157 patients undergoing cardiovascular assessment with 3-year outcomes, the researchers identified polyols that were associated with MACE, and erythritol was among the top MACE-associated molecules.

Next, in a U.S. validation cohort of 2,149 patients, over a 3-year follow-up, patients with plasma levels of erythritol in the highest quartile had a 1.8-fold higher risk of MACE than patients in the lowest quartile (P = .007), after adjusting for cardiovascular risk factors.

In a European validation cohort of 833 patients, over a 3-year follow-up, patients with plasma levels of erythritol in the highest quartile had a 2.21-fold higher risk of MACE than patients in the lowest quartile (P = .010, after adjustment).

At physiologic levels, erythritol enhanced platelet reactivity in vitro and thrombosis formation in vivo.

Finally, in a prospective pilot intervention study, erythritol ingestion in healthy volunteers induced marked and sustained increases in plasma erythritol levels well above thresholds associated with heightened platelet reactivity and thrombosis potential in in vitro and in vivo studies.
 

Others weigh in

“While I think the finding certainly warrants further investigation, don’t throw out your sweeteners just yet,” commented Oliver Jones, PhD, professor of chemistry at the Royal Melbourne Institute of Technology.

“This study only looks at erythritol, and artificial sweeteners are generally considered safe. Any possible (and, as yet unproven) risks of excess erythritol would also need to be balanced against the very real health risks of excess glucose consumption,” he said.

Dr. Hazen responded: “True enough. Erythritol is but one of many artificial sweeteners. That is why it is important to read labels. This study can make patients be informed about how to potentially avoid something that might cause them inadvertent harm.”

“The key findings of this study are that high blood levels of erythritol are strongly associated with cardiovascular outcomes in high-risk patients, which has been replicated in separate validation studies,” said Tom Sanders, DSc, PhD, professor emeritus of nutrition and dietetics, King’s College London.

“Diabetes UK currently advises diabetes patients not to use polyols,” he added.

Dr. Hazen noted that “About three-quarters of the participants had coronary disease, high blood pressure, and about a fifth had diabetes.”

The researchers acknowledge, however, that the observational studies cannot show cause and effect.

The study was supported by the Office of Dietary Supplements at the National Institutes of Health, the Leducq Foundation, and the German Research Foundation (Deutsche Forschungsgemeinschaft). Dr. Mellor, Dr. Jones, and Dr. Sanders have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Increased public health and research efforts to optimize prepregnancy cardiovascular health are needed, particularly among those in under-represented racial and ethnic groups, according to a new scientific statement from the American Heart Association.

“We have released this statement at this time because there is a maternal health crisis in the U.S. with rising maternal morbidity and mortality rates, which are the highest among high-income countries,” chair of the scientific statement writing group, Sadiya S. Khan, MD, told this news organization.

Cardiovascular disease (CVD) is the leading cause of death during pregnancy and the postpartum period and represents 26.5% of pregnancy-related deaths, the statement reports.

“While there is a lot of emphasis in trying to reduce cardiovascular risk during the period of actual pregnancy, much of that risk has often already developed and the women have been living with it for some time, so interventions during pregnancy may be too late,” Dr. Khan, assistant professor of medicine and preventive medicine at Northwestern University, Chicago, said.

“We wanted to try and emphasize the importance of starting to reduce cardiovascular risk earlier before pregnancy. In terms of improving cardiovascular health, this should have benefits both for the mother and the child,” she added.

The statement, “Optimizing Prepregnancy Cardiovascular Health to Improve Outcomes in Pregnant and Postpartum Individuals and Offspring” was published online in a “Go Red For Women” spotlight issue of the AHA publication Circulation.

The statement notes that low levels of prepregnancy cardiovascular health are associated with several pregnancy complications, including hypertensive disorders of pregnancy, preterm birth, small-for-gestational-age birth, and gestational diabetes. Currently, nearly one in five births are complicated by such an adverse pregnancy outcome, and there is a strong association between these complications and risk for subsequent cardiovascular disease.
 

Prepregnancy window

Over the past decade, rates of adverse pregnancy outcomes have increased significantly in the United States, with a near doubling in rates of hypertensive disorders of pregnancy, and there are persistent disparities, with Black individuals significantly more likely to experience adverse pregnancy outcomes, the statement notes.

Emerging data suggest that these complications have, at least in part, prepregnancy origins. Thus, the prepregnancy period may be a critical window during which interventions have a great potential for benefit in both women and their offspring, it says.

The authors suggest a life-course approach to measure, modify, and monitor prepregnancy cardiovascular health, with all clinicians who interact with pregnancy-capable individuals emphasizing optimization of cardiovascular health beginning early in childhood.

“Leveraging these opportunities to target cardiovascular health has the potential to improve health across the life course and for subsequent generations,” they add.
 

Critical research gap

Despite the evidence linking an individual’s prepregnancy health to their offspring’s health, there are no large trials to test whether improving overall cardiovascular health before pregnancy will reduce pregnancy complications, pregnancy-related cardiovascular death, or cardiovascular risk for offspring. The statement authors suggest that such a trial should be considered.

“This would be a big undertaking, but it could be feasible and could be really impactful,” Dr. Khan said. “Of course it would be challenging to recruit women who are planning a pregnancy and to follow them to see if they do get pregnant and consider interventions and outcomes, but given the importance of the need, we think this is something that should be invested in.”

She pointed out that the main way to improve the cardiovascular health of this cohort would be through behavioral counseling on physical activity and diet. “We need to develop strategies tailored to this age group – young women and those who may already have young children – and often the last thing they are thinking about is themselves and their own health.”

She explained that while it is presumed that controlling cardiovascular risk factors will be beneficial, the bigger question is how that can be achieved. “Behavioral interventions are difficult to achieve and often have low adherence, so the focus of the trials should be on strategies on how to deliver behavioral counseling to achieve better cardiovascular health in this population.”

Dr. Khan stressed that any approaches to improving prepregnancy cardiovascular health must address the current racial disparities that are present. “We must make sure that our policies are successful not just in improving cardiovascular health but to ensure it is done equitably. We must find ways to ensure all individuals can access care.”

A version of this article first appeared on Medscape.com.

Increased public health and research efforts to optimize prepregnancy cardiovascular health are needed, particularly among those in under-represented racial and ethnic groups, according to a new scientific statement from the American Heart Association.

“We have released this statement at this time because there is a maternal health crisis in the U.S. with rising maternal morbidity and mortality rates, which are the highest among high-income countries,” chair of the scientific statement writing group, Sadiya S. Khan, MD, told this news organization.

Cardiovascular disease (CVD) is the leading cause of death during pregnancy and the postpartum period and represents 26.5% of pregnancy-related deaths, the statement reports.

“While there is a lot of emphasis in trying to reduce cardiovascular risk during the period of actual pregnancy, much of that risk has often already developed and the women have been living with it for some time, so interventions during pregnancy may be too late,” Dr. Khan, assistant professor of medicine and preventive medicine at Northwestern University, Chicago, said.

“We wanted to try and emphasize the importance of starting to reduce cardiovascular risk earlier before pregnancy. In terms of improving cardiovascular health, this should have benefits both for the mother and the child,” she added.

The statement, “Optimizing Prepregnancy Cardiovascular Health to Improve Outcomes in Pregnant and Postpartum Individuals and Offspring” was published online in a “Go Red For Women” spotlight issue of the AHA publication Circulation.

The statement notes that low levels of prepregnancy cardiovascular health are associated with several pregnancy complications, including hypertensive disorders of pregnancy, preterm birth, small-for-gestational-age birth, and gestational diabetes. Currently, nearly one in five births are complicated by such an adverse pregnancy outcome, and there is a strong association between these complications and risk for subsequent cardiovascular disease.
 

Prepregnancy window

Over the past decade, rates of adverse pregnancy outcomes have increased significantly in the United States, with a near doubling in rates of hypertensive disorders of pregnancy, and there are persistent disparities, with Black individuals significantly more likely to experience adverse pregnancy outcomes, the statement notes.

Emerging data suggest that these complications have, at least in part, prepregnancy origins. Thus, the prepregnancy period may be a critical window during which interventions have a great potential for benefit in both women and their offspring, it says.

The authors suggest a life-course approach to measure, modify, and monitor prepregnancy cardiovascular health, with all clinicians who interact with pregnancy-capable individuals emphasizing optimization of cardiovascular health beginning early in childhood.

“Leveraging these opportunities to target cardiovascular health has the potential to improve health across the life course and for subsequent generations,” they add.
 

Critical research gap

Despite the evidence linking an individual’s prepregnancy health to their offspring’s health, there are no large trials to test whether improving overall cardiovascular health before pregnancy will reduce pregnancy complications, pregnancy-related cardiovascular death, or cardiovascular risk for offspring. The statement authors suggest that such a trial should be considered.

“This would be a big undertaking, but it could be feasible and could be really impactful,” Dr. Khan said. “Of course it would be challenging to recruit women who are planning a pregnancy and to follow them to see if they do get pregnant and consider interventions and outcomes, but given the importance of the need, we think this is something that should be invested in.”

She pointed out that the main way to improve the cardiovascular health of this cohort would be through behavioral counseling on physical activity and diet. “We need to develop strategies tailored to this age group – young women and those who may already have young children – and often the last thing they are thinking about is themselves and their own health.”

She explained that while it is presumed that controlling cardiovascular risk factors will be beneficial, the bigger question is how that can be achieved. “Behavioral interventions are difficult to achieve and often have low adherence, so the focus of the trials should be on strategies on how to deliver behavioral counseling to achieve better cardiovascular health in this population.”

Dr. Khan stressed that any approaches to improving prepregnancy cardiovascular health must address the current racial disparities that are present. “We must make sure that our policies are successful not just in improving cardiovascular health but to ensure it is done equitably. We must find ways to ensure all individuals can access care.”

A version of this article first appeared on Medscape.com.

Increased public health and research efforts to optimize prepregnancy cardiovascular health are needed, particularly among those in under-represented racial and ethnic groups, according to a new scientific statement from the American Heart Association.

“We have released this statement at this time because there is a maternal health crisis in the U.S. with rising maternal morbidity and mortality rates, which are the highest among high-income countries,” chair of the scientific statement writing group, Sadiya S. Khan, MD, told this news organization.

Cardiovascular disease (CVD) is the leading cause of death during pregnancy and the postpartum period and represents 26.5% of pregnancy-related deaths, the statement reports.

“While there is a lot of emphasis in trying to reduce cardiovascular risk during the period of actual pregnancy, much of that risk has often already developed and the women have been living with it for some time, so interventions during pregnancy may be too late,” Dr. Khan, assistant professor of medicine and preventive medicine at Northwestern University, Chicago, said.

“We wanted to try and emphasize the importance of starting to reduce cardiovascular risk earlier before pregnancy. In terms of improving cardiovascular health, this should have benefits both for the mother and the child,” she added.

The statement, “Optimizing Prepregnancy Cardiovascular Health to Improve Outcomes in Pregnant and Postpartum Individuals and Offspring” was published online in a “Go Red For Women” spotlight issue of the AHA publication Circulation.

The statement notes that low levels of prepregnancy cardiovascular health are associated with several pregnancy complications, including hypertensive disorders of pregnancy, preterm birth, small-for-gestational-age birth, and gestational diabetes. Currently, nearly one in five births are complicated by such an adverse pregnancy outcome, and there is a strong association between these complications and risk for subsequent cardiovascular disease.
 

Prepregnancy window

Over the past decade, rates of adverse pregnancy outcomes have increased significantly in the United States, with a near doubling in rates of hypertensive disorders of pregnancy, and there are persistent disparities, with Black individuals significantly more likely to experience adverse pregnancy outcomes, the statement notes.

Emerging data suggest that these complications have, at least in part, prepregnancy origins. Thus, the prepregnancy period may be a critical window during which interventions have a great potential for benefit in both women and their offspring, it says.

The authors suggest a life-course approach to measure, modify, and monitor prepregnancy cardiovascular health, with all clinicians who interact with pregnancy-capable individuals emphasizing optimization of cardiovascular health beginning early in childhood.

“Leveraging these opportunities to target cardiovascular health has the potential to improve health across the life course and for subsequent generations,” they add.
 

Critical research gap

Despite the evidence linking an individual’s prepregnancy health to their offspring’s health, there are no large trials to test whether improving overall cardiovascular health before pregnancy will reduce pregnancy complications, pregnancy-related cardiovascular death, or cardiovascular risk for offspring. The statement authors suggest that such a trial should be considered.

“This would be a big undertaking, but it could be feasible and could be really impactful,” Dr. Khan said. “Of course it would be challenging to recruit women who are planning a pregnancy and to follow them to see if they do get pregnant and consider interventions and outcomes, but given the importance of the need, we think this is something that should be invested in.”

She pointed out that the main way to improve the cardiovascular health of this cohort would be through behavioral counseling on physical activity and diet. “We need to develop strategies tailored to this age group – young women and those who may already have young children – and often the last thing they are thinking about is themselves and their own health.”

She explained that while it is presumed that controlling cardiovascular risk factors will be beneficial, the bigger question is how that can be achieved. “Behavioral interventions are difficult to achieve and often have low adherence, so the focus of the trials should be on strategies on how to deliver behavioral counseling to achieve better cardiovascular health in this population.”

Dr. Khan stressed that any approaches to improving prepregnancy cardiovascular health must address the current racial disparities that are present. “We must make sure that our policies are successful not just in improving cardiovascular health but to ensure it is done equitably. We must find ways to ensure all individuals can access care.”

A version of this article first appeared on Medscape.com.