Cardiology

A new document from the American Heart Association summarizes the latest research on cardiovascular risk factor management in type 2 diabetes, including medications, lifestyle, and social determinants of health.

Despite the availability of effective therapies for improving cardiovascular risk, in the United States fewer than one in five people with type 2 diabetes and without known cardiovascular disease meet control targets for a combination of A1c, blood pressure, LDL cholesterol, and nonsmoking status.

Volkan Ünalan/Thinkstock

That proportion drops to less than 1 in 10 if body mass index less than 30 kg/m² is included among the targets, and even less than that among individuals with established atherosclerotic cardiovascular disease, Joshua J. Joseph, MD, and colleagues point out in their paper, published online Jan. 10 in Circulation.

“This new scientific statement is an urgent call to action to follow the latest evidence-based approaches and to develop new best practices to advance type 2 diabetes treatment and care and reduce cardiovascular disease risk,” wrote Dr. Joseph, assistant professor of medicine in the division of endocrinology, diabetes, and metabolism at The Ohio State University, Columbus, Ohio, and coauthors.

The statement is not a guideline but an expert analysis that may inform future clinical practice guidelines, according to a press release from the AHA.

The new statement reviews evidence through June 2020 for lifestyle management of diabetes and weight, glycemic targets and control, blood pressure management, lipid management, antithrombotic therapy, and screening for cardiovascular and renal complications, including imaging. It also discusses the clinical implications of recent cardiovascular outcomes trials of newer glucose-lowering medications.

However, Dr. Joseph and colleagues point out, clinical care and treatment account for just 10%-20% of modifiable contributors to health outcomes. The other 80%-90% relate to social determinants of health, including health-related behaviors, socioeconomic factors, environmental factors, and racism.

“If we are to continue to advance the management of cardiovascular risk factors, we must also address the [social determinants of health] in the delivery of health care,” they noted.

Overall, they advise a patient-centered approach, meaning “reframing our clinical encounters to think about patients as people who live in families, communities, and societies that must be considered in their cardiovascular risk management.”

“People with [type 2 diabetes] face numerous barriers to health including access to care and equitable care, which must be considered when developing individualized care plans with our patients,” Dr. Joseph said in the AHA press release.
 

Lifestyle, medications for lowering A1c, BP, lipids

For lifestyle management, the authors say, “culturally appropriate recommendations through diabetes self-management education and support and medical nutrition therapy are key to meeting individualized goals for behavioral change and diabetes self-management.”

The document summarizes recommendations from other professional societies regarding glycemic targets and glucose lowering medications, i.e., target A1c levels of either < 7% or < 6.5% for the majority, with adjustments based on individual factors, such as life expectancy. It advises on use of metformin as first-line therapy followed by a sodium-glucose cotransporter-2 inhibitor or a glucagon-like peptide-1 agonist for those with established cardiovascular disease or risk factors.

“Cost may be a barrier to taking some [type 2 diabetes] medications as prescribed; however, many of these medications are now more commonly covered by more health insurance plans,” Dr. Joseph said.

“Another barrier is recognition by patients that these newer [type 2 diabetes] medications are also effective in reducing the risk of heart disease, stroke, heart failure, and kidney disease.”

Blood pressure treatment guidelines differ between those of the AHA/American College of Cardiology (ACC) and the American Diabetes Association (ADA), most notably that the AHA/ACC guidelines advise a general target of < 130/80 mm Hg, whereas ADA advises < 140/90 mm Hg or < 130/80 mm Hg for those with high risk if it can be safely achieved.

The decision should be “patient-centered with shared decision-making,” Dr. Joseph and colleagues advised.

For lipid-lowering, the document cites the 2018 ACC/AHA cholesterol guidelines, which include advising statins as first-line therapy for both primary and secondary prevention in diabetes, with highest intensity statins used in those at highest risk. But again, treatment should be individualized, and other agents should be used for patients in whom statins don’t work or aren’t tolerated.

And while use of antiplatelets – that is, aspirin – is well established as secondary prevention in type 2 diabetes, given new data suggesting that the risk for major bleeding could outweigh the benefits for primary prevention, “the relative benefits of antithrombotic approaches need to be weighed carefully against risks using a patient-centered approach,” the authors advised.

Among the many imaging tests available to facilitate cardiovascular risk stratification in type 2 diabetes, coronary artery calcification (CAC) CT screening is one of the few with sufficient data to support routine use in selected patients. The National Lipid Association, for example, recommends escalation to high-intensity statin for CAC > 100.

“One avenue to continue to address and advance diabetes management is through breaking down the four walls of the clinic or hospital through community engagement, clinic-to-community connections, and academic-community-government partnerships that may help address and support modifiable lifestyle behaviors such as physical activity, nutrition, smoking cessation and stress management,” Dr. Joseph concluded.

The AHA receives funding primarily from individuals. Foundations and corporations, including pharmaceutical, device manufacturers, and other companies, also make donations and fund AHA programs and events. The AHA’s strict policies prevent these relationships from influencing the science content. Revenues from pharmaceutical and biotech companies, device manufacturers, and health insurance providers and the AHA’s financial information are available on the association’s website. Dr. Joseph has disclosed no relevant financial relationships.

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

A new document from the American Heart Association summarizes the latest research on cardiovascular risk factor management in type 2 diabetes, including medications, lifestyle, and social determinants of health.

Despite the availability of effective therapies for improving cardiovascular risk, in the United States fewer than one in five people with type 2 diabetes and without known cardiovascular disease meet control targets for a combination of A1c, blood pressure, LDL cholesterol, and nonsmoking status.

Volkan Ünalan/Thinkstock

That proportion drops to less than 1 in 10 if body mass index less than 30 kg/m² is included among the targets, and even less than that among individuals with established atherosclerotic cardiovascular disease, Joshua J. Joseph, MD, and colleagues point out in their paper, published online Jan. 10 in Circulation.

“This new scientific statement is an urgent call to action to follow the latest evidence-based approaches and to develop new best practices to advance type 2 diabetes treatment and care and reduce cardiovascular disease risk,” wrote Dr. Joseph, assistant professor of medicine in the division of endocrinology, diabetes, and metabolism at The Ohio State University, Columbus, Ohio, and coauthors.

The statement is not a guideline but an expert analysis that may inform future clinical practice guidelines, according to a press release from the AHA.

The new statement reviews evidence through June 2020 for lifestyle management of diabetes and weight, glycemic targets and control, blood pressure management, lipid management, antithrombotic therapy, and screening for cardiovascular and renal complications, including imaging. It also discusses the clinical implications of recent cardiovascular outcomes trials of newer glucose-lowering medications.

However, Dr. Joseph and colleagues point out, clinical care and treatment account for just 10%-20% of modifiable contributors to health outcomes. The other 80%-90% relate to social determinants of health, including health-related behaviors, socioeconomic factors, environmental factors, and racism.

“If we are to continue to advance the management of cardiovascular risk factors, we must also address the [social determinants of health] in the delivery of health care,” they noted.

Overall, they advise a patient-centered approach, meaning “reframing our clinical encounters to think about patients as people who live in families, communities, and societies that must be considered in their cardiovascular risk management.”

“People with [type 2 diabetes] face numerous barriers to health including access to care and equitable care, which must be considered when developing individualized care plans with our patients,” Dr. Joseph said in the AHA press release.
 

Lifestyle, medications for lowering A1c, BP, lipids

For lifestyle management, the authors say, “culturally appropriate recommendations through diabetes self-management education and support and medical nutrition therapy are key to meeting individualized goals for behavioral change and diabetes self-management.”

The document summarizes recommendations from other professional societies regarding glycemic targets and glucose lowering medications, i.e., target A1c levels of either < 7% or < 6.5% for the majority, with adjustments based on individual factors, such as life expectancy. It advises on use of metformin as first-line therapy followed by a sodium-glucose cotransporter-2 inhibitor or a glucagon-like peptide-1 agonist for those with established cardiovascular disease or risk factors.

“Cost may be a barrier to taking some [type 2 diabetes] medications as prescribed; however, many of these medications are now more commonly covered by more health insurance plans,” Dr. Joseph said.

“Another barrier is recognition by patients that these newer [type 2 diabetes] medications are also effective in reducing the risk of heart disease, stroke, heart failure, and kidney disease.”

Blood pressure treatment guidelines differ between those of the AHA/American College of Cardiology (ACC) and the American Diabetes Association (ADA), most notably that the AHA/ACC guidelines advise a general target of < 130/80 mm Hg, whereas ADA advises < 140/90 mm Hg or < 130/80 mm Hg for those with high risk if it can be safely achieved.

The decision should be “patient-centered with shared decision-making,” Dr. Joseph and colleagues advised.

For lipid-lowering, the document cites the 2018 ACC/AHA cholesterol guidelines, which include advising statins as first-line therapy for both primary and secondary prevention in diabetes, with highest intensity statins used in those at highest risk. But again, treatment should be individualized, and other agents should be used for patients in whom statins don’t work or aren’t tolerated.

And while use of antiplatelets – that is, aspirin – is well established as secondary prevention in type 2 diabetes, given new data suggesting that the risk for major bleeding could outweigh the benefits for primary prevention, “the relative benefits of antithrombotic approaches need to be weighed carefully against risks using a patient-centered approach,” the authors advised.

Among the many imaging tests available to facilitate cardiovascular risk stratification in type 2 diabetes, coronary artery calcification (CAC) CT screening is one of the few with sufficient data to support routine use in selected patients. The National Lipid Association, for example, recommends escalation to high-intensity statin for CAC > 100.

“One avenue to continue to address and advance diabetes management is through breaking down the four walls of the clinic or hospital through community engagement, clinic-to-community connections, and academic-community-government partnerships that may help address and support modifiable lifestyle behaviors such as physical activity, nutrition, smoking cessation and stress management,” Dr. Joseph concluded.

The AHA receives funding primarily from individuals. Foundations and corporations, including pharmaceutical, device manufacturers, and other companies, also make donations and fund AHA programs and events. The AHA’s strict policies prevent these relationships from influencing the science content. Revenues from pharmaceutical and biotech companies, device manufacturers, and health insurance providers and the AHA’s financial information are available on the association’s website. Dr. Joseph has disclosed no relevant financial relationships.

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

A new document from the American Heart Association summarizes the latest research on cardiovascular risk factor management in type 2 diabetes, including medications, lifestyle, and social determinants of health.

Despite the availability of effective therapies for improving cardiovascular risk, in the United States fewer than one in five people with type 2 diabetes and without known cardiovascular disease meet control targets for a combination of A1c, blood pressure, LDL cholesterol, and nonsmoking status.

Volkan Ünalan/Thinkstock

That proportion drops to less than 1 in 10 if body mass index less than 30 kg/m² is included among the targets, and even less than that among individuals with established atherosclerotic cardiovascular disease, Joshua J. Joseph, MD, and colleagues point out in their paper, published online Jan. 10 in Circulation.

“This new scientific statement is an urgent call to action to follow the latest evidence-based approaches and to develop new best practices to advance type 2 diabetes treatment and care and reduce cardiovascular disease risk,” wrote Dr. Joseph, assistant professor of medicine in the division of endocrinology, diabetes, and metabolism at The Ohio State University, Columbus, Ohio, and coauthors.

The statement is not a guideline but an expert analysis that may inform future clinical practice guidelines, according to a press release from the AHA.

The new statement reviews evidence through June 2020 for lifestyle management of diabetes and weight, glycemic targets and control, blood pressure management, lipid management, antithrombotic therapy, and screening for cardiovascular and renal complications, including imaging. It also discusses the clinical implications of recent cardiovascular outcomes trials of newer glucose-lowering medications.

However, Dr. Joseph and colleagues point out, clinical care and treatment account for just 10%-20% of modifiable contributors to health outcomes. The other 80%-90% relate to social determinants of health, including health-related behaviors, socioeconomic factors, environmental factors, and racism.

“If we are to continue to advance the management of cardiovascular risk factors, we must also address the [social determinants of health] in the delivery of health care,” they noted.

Overall, they advise a patient-centered approach, meaning “reframing our clinical encounters to think about patients as people who live in families, communities, and societies that must be considered in their cardiovascular risk management.”

“People with [type 2 diabetes] face numerous barriers to health including access to care and equitable care, which must be considered when developing individualized care plans with our patients,” Dr. Joseph said in the AHA press release.
 

Lifestyle, medications for lowering A1c, BP, lipids

For lifestyle management, the authors say, “culturally appropriate recommendations through diabetes self-management education and support and medical nutrition therapy are key to meeting individualized goals for behavioral change and diabetes self-management.”

The document summarizes recommendations from other professional societies regarding glycemic targets and glucose lowering medications, i.e., target A1c levels of either < 7% or < 6.5% for the majority, with adjustments based on individual factors, such as life expectancy. It advises on use of metformin as first-line therapy followed by a sodium-glucose cotransporter-2 inhibitor or a glucagon-like peptide-1 agonist for those with established cardiovascular disease or risk factors.

“Cost may be a barrier to taking some [type 2 diabetes] medications as prescribed; however, many of these medications are now more commonly covered by more health insurance plans,” Dr. Joseph said.

“Another barrier is recognition by patients that these newer [type 2 diabetes] medications are also effective in reducing the risk of heart disease, stroke, heart failure, and kidney disease.”

Blood pressure treatment guidelines differ between those of the AHA/American College of Cardiology (ACC) and the American Diabetes Association (ADA), most notably that the AHA/ACC guidelines advise a general target of < 130/80 mm Hg, whereas ADA advises < 140/90 mm Hg or < 130/80 mm Hg for those with high risk if it can be safely achieved.

The decision should be “patient-centered with shared decision-making,” Dr. Joseph and colleagues advised.

For lipid-lowering, the document cites the 2018 ACC/AHA cholesterol guidelines, which include advising statins as first-line therapy for both primary and secondary prevention in diabetes, with highest intensity statins used in those at highest risk. But again, treatment should be individualized, and other agents should be used for patients in whom statins don’t work or aren’t tolerated.

And while use of antiplatelets – that is, aspirin – is well established as secondary prevention in type 2 diabetes, given new data suggesting that the risk for major bleeding could outweigh the benefits for primary prevention, “the relative benefits of antithrombotic approaches need to be weighed carefully against risks using a patient-centered approach,” the authors advised.

Among the many imaging tests available to facilitate cardiovascular risk stratification in type 2 diabetes, coronary artery calcification (CAC) CT screening is one of the few with sufficient data to support routine use in selected patients. The National Lipid Association, for example, recommends escalation to high-intensity statin for CAC > 100.

“One avenue to continue to address and advance diabetes management is through breaking down the four walls of the clinic or hospital through community engagement, clinic-to-community connections, and academic-community-government partnerships that may help address and support modifiable lifestyle behaviors such as physical activity, nutrition, smoking cessation and stress management,” Dr. Joseph concluded.

The AHA receives funding primarily from individuals. Foundations and corporations, including pharmaceutical, device manufacturers, and other companies, also make donations and fund AHA programs and events. The AHA’s strict policies prevent these relationships from influencing the science content. Revenues from pharmaceutical and biotech companies, device manufacturers, and health insurance providers and the AHA’s financial information are available on the association’s website. Dr. Joseph has disclosed no relevant financial relationships.

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

In 2014, when the Food and Drug Administration found serious problems with a life-sustaining heart pump, its warning letter to the manufacturer threatened to notify other federal health agencies about the inspection’s findings.

But for years, no such alert ever went out. Instead, the agency added the warning letter to an online database alongside thousands of others, following its typical procedures, an FDA spokesperson said.

Agencies such as the Centers for Medicare & Medicaid Services and the U.S. Department of Veterans Affairs went on paying to implant the HeartWare Ventricular Assist Device, or HVAD, in new patients even though federal inspectors had found problems with the device linked to patient deaths and injuries.

Taxpayer dollars continued to flow to the original device maker, HeartWare, and then to the company that acquired it in 2016, Medtronic, for 7 years while the issues raised in the warning letter remained unresolved.

If crucial safety information in FDA warning letters doesn’t make it to other arms of the government responsible for deciding which medical devices to pay for, experts said patients are the ones put at risk.

“It’s clearly a breakdown of communication,” said Dr. Rita Redberg, a cardiologist at the University of California, San Francisco, who researches medical device safety and regulation. “It’s not just the money, obviously. It’s people’s lives.”

The FDA acknowledged that it doesn’t directly notify other agencies when it issues warning letters, pointing instead to its online database, which is accessible to both government officials and the public. “The FDA’s decisions are intended to be patient-centric with the health and safety of device users as our highest priority,” the agency spokesperson said in an email.

The HeartWare letter was removed from the public database about 2 years ago, even though the problems remained unresolved and patients were still receiving implants. The database clears out letters that are more than 5 years old.

CMS, which oversees the Medicare and Medicaid programs, would not say why it continued paying for a device that didn’t meet government standards. It directed questions about the HeartWare warning letter to the FDA. “CMS does not have oversight of the manufacturing and related safety assessments of a medical device manufacturer,” a spokesperson said in an email.

The spokesperson noted that CMS requires heart pump patients to have specialized medical teams managing their care, which should monitor FDA communications regarding safety of devices.

CMS doesn’t track data on devices by manufacturer, so it’s essentially impossible to calculate its total spending on HVADs. One 2018 medical journal study found that Medicare and Medicaid paid for more than half the cost of all heart pump implants from 2009 to 2014. If that rate of spending continued, CMS may have spent more than $400 million on implanting HVADs since 2014.

A spokesperson for the VA said his agency was never notified about the HeartWare warning letter. The VA paid HeartWare and Medtronic more than $3 million after the FDA issued the letter in 2014. It offered this explanation for why: “It’s important to note that FDA Warning Letters are notifications issued to manufacturers found to be in significant violation of federal regulations. They are not product recalls.”

In the case of the HVAD, the FDA’s failure to make sure its warning reached beyond the manufacturer may have had life-and-death consequences.

In August, ProPublica reported that federal inspectors continued finding problems at the HVAD’s manufacturing plant for years. Meanwhile, the FDA received thousands of reports of suspicious deaths and injuries and more than a dozen high-risk safety alerts from the manufacturer.

The documents detailed one horrifying device failure after another. A father of four died after his device suddenly failed and his teenage daughter couldn’t resuscitate him. Another patient’s heart tissue was charred after a pump short-circuited and overheated. A teenager died after vomiting blood as his mother struggled to restart a defective pump.

In June, Medtronic ended sales and implants of the device, citing new data that showed patients with HVADs had a higher rate of deaths and strokes than those with a competing heart pump.

Medtronic declined to comment for this story. It has previously said it believed that after the 2014 warning letter the benefits of the HVAD still outweighed the risks for patients with severe heart failure.

Experts said the lack of communication between federal agencies when serious device problems are found is baffling but not surprising. It fits a broader trend of device regulators focusing more on evaluating new products than monitoring the ones already on the market.

“The priority is to get more medical devices out there, paid for and getting used,” said Dr. Joseph Ross, a professor of medicine and public health at Yale University who studies medical device regulation.

Other U.S. health care regulators move more forcefully when providers and suppliers don’t meet the government’s minimum safety requirements for an extended period, putting patients at risk.

Take hospitals. When inspectors find a facility is not meeting safety standards, CMS can issue an immediate jeopardy citation and, if problems aren’t fixed, move to withhold federal payments, which make up substantial portions of most hospitals’ revenues. In the rare cases when hospitals don’t take sufficient action, CMS follows through and revokes funding.

Redberg, the UCSF cardiologist, said the lack of similar action for medical devices offers a clear “opportunity for improvement.” At minimum, the FDA could establish processes to directly inform other agencies when it issues warning letters and finds serious problems with devices being sold in the United States.

“If the agency’s mission is to protect public health, they would want to do these things and move quickly,” she said.

This story was originally published on ProPublica. ProPublica is a nonprofit newsroom that investigates abuses of power. Sign up to receive their biggest stories as soon as they’re published.

In 2014, when the Food and Drug Administration found serious problems with a life-sustaining heart pump, its warning letter to the manufacturer threatened to notify other federal health agencies about the inspection’s findings.

But for years, no such alert ever went out. Instead, the agency added the warning letter to an online database alongside thousands of others, following its typical procedures, an FDA spokesperson said.

Agencies such as the Centers for Medicare & Medicaid Services and the U.S. Department of Veterans Affairs went on paying to implant the HeartWare Ventricular Assist Device, or HVAD, in new patients even though federal inspectors had found problems with the device linked to patient deaths and injuries.

Taxpayer dollars continued to flow to the original device maker, HeartWare, and then to the company that acquired it in 2016, Medtronic, for 7 years while the issues raised in the warning letter remained unresolved.

If crucial safety information in FDA warning letters doesn’t make it to other arms of the government responsible for deciding which medical devices to pay for, experts said patients are the ones put at risk.

“It’s clearly a breakdown of communication,” said Dr. Rita Redberg, a cardiologist at the University of California, San Francisco, who researches medical device safety and regulation. “It’s not just the money, obviously. It’s people’s lives.”

The FDA acknowledged that it doesn’t directly notify other agencies when it issues warning letters, pointing instead to its online database, which is accessible to both government officials and the public. “The FDA’s decisions are intended to be patient-centric with the health and safety of device users as our highest priority,” the agency spokesperson said in an email.

The HeartWare letter was removed from the public database about 2 years ago, even though the problems remained unresolved and patients were still receiving implants. The database clears out letters that are more than 5 years old.

CMS, which oversees the Medicare and Medicaid programs, would not say why it continued paying for a device that didn’t meet government standards. It directed questions about the HeartWare warning letter to the FDA. “CMS does not have oversight of the manufacturing and related safety assessments of a medical device manufacturer,” a spokesperson said in an email.

The spokesperson noted that CMS requires heart pump patients to have specialized medical teams managing their care, which should monitor FDA communications regarding safety of devices.

CMS doesn’t track data on devices by manufacturer, so it’s essentially impossible to calculate its total spending on HVADs. One 2018 medical journal study found that Medicare and Medicaid paid for more than half the cost of all heart pump implants from 2009 to 2014. If that rate of spending continued, CMS may have spent more than $400 million on implanting HVADs since 2014.

A spokesperson for the VA said his agency was never notified about the HeartWare warning letter. The VA paid HeartWare and Medtronic more than $3 million after the FDA issued the letter in 2014. It offered this explanation for why: “It’s important to note that FDA Warning Letters are notifications issued to manufacturers found to be in significant violation of federal regulations. They are not product recalls.”

In the case of the HVAD, the FDA’s failure to make sure its warning reached beyond the manufacturer may have had life-and-death consequences.

In August, ProPublica reported that federal inspectors continued finding problems at the HVAD’s manufacturing plant for years. Meanwhile, the FDA received thousands of reports of suspicious deaths and injuries and more than a dozen high-risk safety alerts from the manufacturer.

The documents detailed one horrifying device failure after another. A father of four died after his device suddenly failed and his teenage daughter couldn’t resuscitate him. Another patient’s heart tissue was charred after a pump short-circuited and overheated. A teenager died after vomiting blood as his mother struggled to restart a defective pump.

In June, Medtronic ended sales and implants of the device, citing new data that showed patients with HVADs had a higher rate of deaths and strokes than those with a competing heart pump.

Medtronic declined to comment for this story. It has previously said it believed that after the 2014 warning letter the benefits of the HVAD still outweighed the risks for patients with severe heart failure.

Experts said the lack of communication between federal agencies when serious device problems are found is baffling but not surprising. It fits a broader trend of device regulators focusing more on evaluating new products than monitoring the ones already on the market.

“The priority is to get more medical devices out there, paid for and getting used,” said Dr. Joseph Ross, a professor of medicine and public health at Yale University who studies medical device regulation.

Other U.S. health care regulators move more forcefully when providers and suppliers don’t meet the government’s minimum safety requirements for an extended period, putting patients at risk.

Take hospitals. When inspectors find a facility is not meeting safety standards, CMS can issue an immediate jeopardy citation and, if problems aren’t fixed, move to withhold federal payments, which make up substantial portions of most hospitals’ revenues. In the rare cases when hospitals don’t take sufficient action, CMS follows through and revokes funding.

Redberg, the UCSF cardiologist, said the lack of similar action for medical devices offers a clear “opportunity for improvement.” At minimum, the FDA could establish processes to directly inform other agencies when it issues warning letters and finds serious problems with devices being sold in the United States.

“If the agency’s mission is to protect public health, they would want to do these things and move quickly,” she said.

This story was originally published on ProPublica. ProPublica is a nonprofit newsroom that investigates abuses of power. Sign up to receive their biggest stories as soon as they’re published.

In 2014, when the Food and Drug Administration found serious problems with a life-sustaining heart pump, its warning letter to the manufacturer threatened to notify other federal health agencies about the inspection’s findings.

But for years, no such alert ever went out. Instead, the agency added the warning letter to an online database alongside thousands of others, following its typical procedures, an FDA spokesperson said.

Agencies such as the Centers for Medicare & Medicaid Services and the U.S. Department of Veterans Affairs went on paying to implant the HeartWare Ventricular Assist Device, or HVAD, in new patients even though federal inspectors had found problems with the device linked to patient deaths and injuries.

Taxpayer dollars continued to flow to the original device maker, HeartWare, and then to the company that acquired it in 2016, Medtronic, for 7 years while the issues raised in the warning letter remained unresolved.

If crucial safety information in FDA warning letters doesn’t make it to other arms of the government responsible for deciding which medical devices to pay for, experts said patients are the ones put at risk.

“It’s clearly a breakdown of communication,” said Dr. Rita Redberg, a cardiologist at the University of California, San Francisco, who researches medical device safety and regulation. “It’s not just the money, obviously. It’s people’s lives.”

The FDA acknowledged that it doesn’t directly notify other agencies when it issues warning letters, pointing instead to its online database, which is accessible to both government officials and the public. “The FDA’s decisions are intended to be patient-centric with the health and safety of device users as our highest priority,” the agency spokesperson said in an email.

The HeartWare letter was removed from the public database about 2 years ago, even though the problems remained unresolved and patients were still receiving implants. The database clears out letters that are more than 5 years old.

CMS, which oversees the Medicare and Medicaid programs, would not say why it continued paying for a device that didn’t meet government standards. It directed questions about the HeartWare warning letter to the FDA. “CMS does not have oversight of the manufacturing and related safety assessments of a medical device manufacturer,” a spokesperson said in an email.

The spokesperson noted that CMS requires heart pump patients to have specialized medical teams managing their care, which should monitor FDA communications regarding safety of devices.

CMS doesn’t track data on devices by manufacturer, so it’s essentially impossible to calculate its total spending on HVADs. One 2018 medical journal study found that Medicare and Medicaid paid for more than half the cost of all heart pump implants from 2009 to 2014. If that rate of spending continued, CMS may have spent more than $400 million on implanting HVADs since 2014.

A spokesperson for the VA said his agency was never notified about the HeartWare warning letter. The VA paid HeartWare and Medtronic more than $3 million after the FDA issued the letter in 2014. It offered this explanation for why: “It’s important to note that FDA Warning Letters are notifications issued to manufacturers found to be in significant violation of federal regulations. They are not product recalls.”

In the case of the HVAD, the FDA’s failure to make sure its warning reached beyond the manufacturer may have had life-and-death consequences.

In August, ProPublica reported that federal inspectors continued finding problems at the HVAD’s manufacturing plant for years. Meanwhile, the FDA received thousands of reports of suspicious deaths and injuries and more than a dozen high-risk safety alerts from the manufacturer.

The documents detailed one horrifying device failure after another. A father of four died after his device suddenly failed and his teenage daughter couldn’t resuscitate him. Another patient’s heart tissue was charred after a pump short-circuited and overheated. A teenager died after vomiting blood as his mother struggled to restart a defective pump.

In June, Medtronic ended sales and implants of the device, citing new data that showed patients with HVADs had a higher rate of deaths and strokes than those with a competing heart pump.

Medtronic declined to comment for this story. It has previously said it believed that after the 2014 warning letter the benefits of the HVAD still outweighed the risks for patients with severe heart failure.

Experts said the lack of communication between federal agencies when serious device problems are found is baffling but not surprising. It fits a broader trend of device regulators focusing more on evaluating new products than monitoring the ones already on the market.

“The priority is to get more medical devices out there, paid for and getting used,” said Dr. Joseph Ross, a professor of medicine and public health at Yale University who studies medical device regulation.

Other U.S. health care regulators move more forcefully when providers and suppliers don’t meet the government’s minimum safety requirements for an extended period, putting patients at risk.

Take hospitals. When inspectors find a facility is not meeting safety standards, CMS can issue an immediate jeopardy citation and, if problems aren’t fixed, move to withhold federal payments, which make up substantial portions of most hospitals’ revenues. In the rare cases when hospitals don’t take sufficient action, CMS follows through and revokes funding.

Redberg, the UCSF cardiologist, said the lack of similar action for medical devices offers a clear “opportunity for improvement.” At minimum, the FDA could establish processes to directly inform other agencies when it issues warning letters and finds serious problems with devices being sold in the United States.

“If the agency’s mission is to protect public health, they would want to do these things and move quickly,” she said.

This story was originally published on ProPublica. ProPublica is a nonprofit newsroom that investigates abuses of power. Sign up to receive their biggest stories as soon as they’re published.

The damage to the heart caused by a myocardial infarction is not just a result of ischemia caused by the blocked artery but is also brought about by bleeding in the myocardium after the artery has been opened, a new study suggests.

This observation is leading to new approaches to limiting infarct size and treating MI.

“In MI treatment, we have always focused on opening up the artery as quickly as possible to limit the myocardial damage caused by ischemia,” the study’s senior author, Rohan Dharmakumar, PhD, Indiana University, Indianapolis, told this news organization.

“We are pursuing a completely new approach focusing on limiting the damage after revascularization,” he said. “We are totally rethinking what a myocardial infarction is – what causes the injury and the time course of the injury – our results suggest that it’s not just ischemic damage and a lot of the harm is caused by hemorrhage after reperfusion.”

It has been known for many years that hemorrhage is often seen in the myocardium in large MIs, but it has not been established before now whether it contributes to the injury or not, Dr. Dharmakumar explained.

“This study was done to look at that – and we found that the hemorrhage drives a second layer of injury on top of the ischemia.”

Dr. Dharmakumar said this hemorrhage is part of the phenomenon known as reperfusion injury. “This has been known to exist for many years, but we haven’t fully understood all the factors contributing to it. Our results suggest that hemorrhage is a major component of reperfusion injury – probably the dominant factor,” he said.  

The researchers are now working on therapeutic approaches to try to prevent this hemorrhage and/or to minimize its effect.

“We are studying how hemorrhage drives damage and how to block these biological processes,” Dr. Dharmakumar said. “Our studies suggest that hemorrhage could account for up to half of the damage caused by a myocardial infarction. If we can limit that, we should be able to reduce the size of the infarct and this should translate into better long-term outcomes.

“I’m very excited about these results,” he added. “We are already seeing a remarkable improvement in animal models with some of the potential therapeutic approaches we are working on.”

The current study is published in the January 2022 issue of the Journal of the American College of Cardiology (JACC).

The authors explain that it is now recognized that reperfusion injury can contribute to increasing infarct size, which they refer to as “infarct surge.” Previous studies have also shown that reperfusion injury can contribute to as much as 50% of the final infarct size, but the factors contributing to the observed variability are not known, and previous attempts to limit infarct surge from reperfusion injury have failed.

They noted that after reperfusion, microvessels can remain obstructed, resulting in intramyocardial hemorrhage. They conducted the current study to investigate whether such hemorrhage causes expansion of the infarct.

They studied 70 patients with ST-segment elevation MI who were categorized with cardiovascular MRI to have intramyocardial hemorrhage or not following primary PCI, and for whom serial cardiac troponin measures were used to assess infarct size.

Results showed that while troponin levels were not different before reperfusion, patients with intramyocardial hemorrhage had significantly higher cardiac troponin levels after reperfusion and these levels peaked earlier than in patients without hemorrhage.

In animal models, those with intramyocardial hemorrhage had a more rapid expansion of myocardial necrosis than did those without hemorrhage, and within 72 hours of reperfusion, a fourfold greater loss in salvageable myocardium was evident in hemorrhagic MIs.

“We have shown that damage to the heart continues after revascularization as measured by rapidly increasing troponin levels in the hearts that have had a hemorrhage,” Dr. Dharmakumar said.

“Hemorrhage in the myocardium was associated with larger infarctions, and in infarcts causing the same area of myocardium to be at risk, those with hemorrhage after revascularization lost a lot more of the salvageable myocardium than those without hemorrhage,” he added.

Dr. Dharmakumar estimates that such hemorrhage occurs in about half of MIs after revascularization, with risk factors including male gender, anterior wall MIs, and smoking.

He pointed out that previous attempts to treat or prevent reperfusion injury have not been successful, probably because they have not been addressing the key mechanism. “We have not been looking at hemorrhage in this regard until now. This is because it is only recently that we have had the tools to be able to identify hemorrhage in the heart with the use of cardiac MRI.” 
 

Final frontier

In an accompanying editorial, Colin Berry, MBChB, University of Glasgow, and Borja Ibáñez, MD, Jiménez Díaz Foundation University Hospital, Madrid, said they applaud the investigators for providing new, mechanistic insights into a difficult clinical problem that has an unmet therapeutic need.

But they pointed out that it is difficult to completely dissect the impact of hemorrhage versus MI size on adverse remodeling, noting that it might be the case that more severe ischemia/reperfusion events are associated with large MI sizes and higher degree of hemorrhage.

However, they concluded that: “Intramyocardial hemorrhage represents the final frontier for preventing heart failure post-MI. It is readily detected using CMR, and clinical research of novel therapeutic approaches merits prioritization.”

This work was supported by grants from National Institutes of Health/National Heart, Lung, and Blood Institute. Dr. Dharmakumar and coauthor Robert Finney, PhD, have ownership interest in Cardiotheranostics. Dr. Berry is employed by the University of Glasgow, which holds consultancy and research agreements for his work with Abbott Vascular, AstraZeneca, Boehringer Ingelheim, Causeway Therapeutics, Coroventis, Genentech, GlaxoSmithKline, HeartFlow, Menarini, Neovasc, Siemens Healthcare, and Valo Health.

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

The damage to the heart caused by a myocardial infarction is not just a result of ischemia caused by the blocked artery but is also brought about by bleeding in the myocardium after the artery has been opened, a new study suggests.

This observation is leading to new approaches to limiting infarct size and treating MI.

“In MI treatment, we have always focused on opening up the artery as quickly as possible to limit the myocardial damage caused by ischemia,” the study’s senior author, Rohan Dharmakumar, PhD, Indiana University, Indianapolis, told this news organization.

“We are pursuing a completely new approach focusing on limiting the damage after revascularization,” he said. “We are totally rethinking what a myocardial infarction is – what causes the injury and the time course of the injury – our results suggest that it’s not just ischemic damage and a lot of the harm is caused by hemorrhage after reperfusion.”

It has been known for many years that hemorrhage is often seen in the myocardium in large MIs, but it has not been established before now whether it contributes to the injury or not, Dr. Dharmakumar explained.

“This study was done to look at that – and we found that the hemorrhage drives a second layer of injury on top of the ischemia.”

Dr. Dharmakumar said this hemorrhage is part of the phenomenon known as reperfusion injury. “This has been known to exist for many years, but we haven’t fully understood all the factors contributing to it. Our results suggest that hemorrhage is a major component of reperfusion injury – probably the dominant factor,” he said.  

The researchers are now working on therapeutic approaches to try to prevent this hemorrhage and/or to minimize its effect.

“We are studying how hemorrhage drives damage and how to block these biological processes,” Dr. Dharmakumar said. “Our studies suggest that hemorrhage could account for up to half of the damage caused by a myocardial infarction. If we can limit that, we should be able to reduce the size of the infarct and this should translate into better long-term outcomes.

“I’m very excited about these results,” he added. “We are already seeing a remarkable improvement in animal models with some of the potential therapeutic approaches we are working on.”

The current study is published in the January 2022 issue of the Journal of the American College of Cardiology (JACC).

The authors explain that it is now recognized that reperfusion injury can contribute to increasing infarct size, which they refer to as “infarct surge.” Previous studies have also shown that reperfusion injury can contribute to as much as 50% of the final infarct size, but the factors contributing to the observed variability are not known, and previous attempts to limit infarct surge from reperfusion injury have failed.

They noted that after reperfusion, microvessels can remain obstructed, resulting in intramyocardial hemorrhage. They conducted the current study to investigate whether such hemorrhage causes expansion of the infarct.

They studied 70 patients with ST-segment elevation MI who were categorized with cardiovascular MRI to have intramyocardial hemorrhage or not following primary PCI, and for whom serial cardiac troponin measures were used to assess infarct size.

Results showed that while troponin levels were not different before reperfusion, patients with intramyocardial hemorrhage had significantly higher cardiac troponin levels after reperfusion and these levels peaked earlier than in patients without hemorrhage.

In animal models, those with intramyocardial hemorrhage had a more rapid expansion of myocardial necrosis than did those without hemorrhage, and within 72 hours of reperfusion, a fourfold greater loss in salvageable myocardium was evident in hemorrhagic MIs.

“We have shown that damage to the heart continues after revascularization as measured by rapidly increasing troponin levels in the hearts that have had a hemorrhage,” Dr. Dharmakumar said.

“Hemorrhage in the myocardium was associated with larger infarctions, and in infarcts causing the same area of myocardium to be at risk, those with hemorrhage after revascularization lost a lot more of the salvageable myocardium than those without hemorrhage,” he added.

Dr. Dharmakumar estimates that such hemorrhage occurs in about half of MIs after revascularization, with risk factors including male gender, anterior wall MIs, and smoking.

He pointed out that previous attempts to treat or prevent reperfusion injury have not been successful, probably because they have not been addressing the key mechanism. “We have not been looking at hemorrhage in this regard until now. This is because it is only recently that we have had the tools to be able to identify hemorrhage in the heart with the use of cardiac MRI.” 
 

Final frontier

In an accompanying editorial, Colin Berry, MBChB, University of Glasgow, and Borja Ibáñez, MD, Jiménez Díaz Foundation University Hospital, Madrid, said they applaud the investigators for providing new, mechanistic insights into a difficult clinical problem that has an unmet therapeutic need.

But they pointed out that it is difficult to completely dissect the impact of hemorrhage versus MI size on adverse remodeling, noting that it might be the case that more severe ischemia/reperfusion events are associated with large MI sizes and higher degree of hemorrhage.

However, they concluded that: “Intramyocardial hemorrhage represents the final frontier for preventing heart failure post-MI. It is readily detected using CMR, and clinical research of novel therapeutic approaches merits prioritization.”

This work was supported by grants from National Institutes of Health/National Heart, Lung, and Blood Institute. Dr. Dharmakumar and coauthor Robert Finney, PhD, have ownership interest in Cardiotheranostics. Dr. Berry is employed by the University of Glasgow, which holds consultancy and research agreements for his work with Abbott Vascular, AstraZeneca, Boehringer Ingelheim, Causeway Therapeutics, Coroventis, Genentech, GlaxoSmithKline, HeartFlow, Menarini, Neovasc, Siemens Healthcare, and Valo Health.

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

The damage to the heart caused by a myocardial infarction is not just a result of ischemia caused by the blocked artery but is also brought about by bleeding in the myocardium after the artery has been opened, a new study suggests.

This observation is leading to new approaches to limiting infarct size and treating MI.

“In MI treatment, we have always focused on opening up the artery as quickly as possible to limit the myocardial damage caused by ischemia,” the study’s senior author, Rohan Dharmakumar, PhD, Indiana University, Indianapolis, told this news organization.

“We are pursuing a completely new approach focusing on limiting the damage after revascularization,” he said. “We are totally rethinking what a myocardial infarction is – what causes the injury and the time course of the injury – our results suggest that it’s not just ischemic damage and a lot of the harm is caused by hemorrhage after reperfusion.”

It has been known for many years that hemorrhage is often seen in the myocardium in large MIs, but it has not been established before now whether it contributes to the injury or not, Dr. Dharmakumar explained.

“This study was done to look at that – and we found that the hemorrhage drives a second layer of injury on top of the ischemia.”

Dr. Dharmakumar said this hemorrhage is part of the phenomenon known as reperfusion injury. “This has been known to exist for many years, but we haven’t fully understood all the factors contributing to it. Our results suggest that hemorrhage is a major component of reperfusion injury – probably the dominant factor,” he said.  

The researchers are now working on therapeutic approaches to try to prevent this hemorrhage and/or to minimize its effect.

“We are studying how hemorrhage drives damage and how to block these biological processes,” Dr. Dharmakumar said. “Our studies suggest that hemorrhage could account for up to half of the damage caused by a myocardial infarction. If we can limit that, we should be able to reduce the size of the infarct and this should translate into better long-term outcomes.

“I’m very excited about these results,” he added. “We are already seeing a remarkable improvement in animal models with some of the potential therapeutic approaches we are working on.”

The current study is published in the January 2022 issue of the Journal of the American College of Cardiology (JACC).

The authors explain that it is now recognized that reperfusion injury can contribute to increasing infarct size, which they refer to as “infarct surge.” Previous studies have also shown that reperfusion injury can contribute to as much as 50% of the final infarct size, but the factors contributing to the observed variability are not known, and previous attempts to limit infarct surge from reperfusion injury have failed.

They noted that after reperfusion, microvessels can remain obstructed, resulting in intramyocardial hemorrhage. They conducted the current study to investigate whether such hemorrhage causes expansion of the infarct.

They studied 70 patients with ST-segment elevation MI who were categorized with cardiovascular MRI to have intramyocardial hemorrhage or not following primary PCI, and for whom serial cardiac troponin measures were used to assess infarct size.

Results showed that while troponin levels were not different before reperfusion, patients with intramyocardial hemorrhage had significantly higher cardiac troponin levels after reperfusion and these levels peaked earlier than in patients without hemorrhage.

In animal models, those with intramyocardial hemorrhage had a more rapid expansion of myocardial necrosis than did those without hemorrhage, and within 72 hours of reperfusion, a fourfold greater loss in salvageable myocardium was evident in hemorrhagic MIs.

“We have shown that damage to the heart continues after revascularization as measured by rapidly increasing troponin levels in the hearts that have had a hemorrhage,” Dr. Dharmakumar said.

“Hemorrhage in the myocardium was associated with larger infarctions, and in infarcts causing the same area of myocardium to be at risk, those with hemorrhage after revascularization lost a lot more of the salvageable myocardium than those without hemorrhage,” he added.

Dr. Dharmakumar estimates that such hemorrhage occurs in about half of MIs after revascularization, with risk factors including male gender, anterior wall MIs, and smoking.

He pointed out that previous attempts to treat or prevent reperfusion injury have not been successful, probably because they have not been addressing the key mechanism. “We have not been looking at hemorrhage in this regard until now. This is because it is only recently that we have had the tools to be able to identify hemorrhage in the heart with the use of cardiac MRI.” 
 

Final frontier

In an accompanying editorial, Colin Berry, MBChB, University of Glasgow, and Borja Ibáñez, MD, Jiménez Díaz Foundation University Hospital, Madrid, said they applaud the investigators for providing new, mechanistic insights into a difficult clinical problem that has an unmet therapeutic need.

But they pointed out that it is difficult to completely dissect the impact of hemorrhage versus MI size on adverse remodeling, noting that it might be the case that more severe ischemia/reperfusion events are associated with large MI sizes and higher degree of hemorrhage.

However, they concluded that: “Intramyocardial hemorrhage represents the final frontier for preventing heart failure post-MI. It is readily detected using CMR, and clinical research of novel therapeutic approaches merits prioritization.”

This work was supported by grants from National Institutes of Health/National Heart, Lung, and Blood Institute. Dr. Dharmakumar and coauthor Robert Finney, PhD, have ownership interest in Cardiotheranostics. Dr. Berry is employed by the University of Glasgow, which holds consultancy and research agreements for his work with Abbott Vascular, AstraZeneca, Boehringer Ingelheim, Causeway Therapeutics, Coroventis, Genentech, GlaxoSmithKline, HeartFlow, Menarini, Neovasc, Siemens Healthcare, and Valo Health.

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

Patients with complex coronary artery disease (CAD) – either three-vessel disease and/or left main disease – who also had heavy coronary artery calcification (CAC) had greater all-cause mortality 10 years after revascularization, compared with those without such lesions.

However, perhaps unexpectedly, patients with heavily calcified lesions (HCLs) had similar 10-year survival whether they had undergone coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI).

These findings from a post hoc analysis of the SYNTAX Extended Survival (SYNTAXES) study led by Hideyuki Kawashima, MD, PhD, National University of Ireland, Galway, and the University of Amsterdam, were published online Dec. 29, 2021, in JACC: Cardiovascular Interventions.

“There was an apparent lack of benefit at very long-term with CABG versus PCI in the presence of HCL,” Dr. Kawashima and corresponding author Patrick W. Serruys, MD, PhD, National University of Ireland and Imperial College London, summarized in a joint email to this news organization.

“Since HCLs – the final status of atherosclerosis and inflammation – reflect the aging process, complexity, and extensiveness of CAD, and comorbidity, it is possible that the currently available revascularization methods do not provide benefit in the prevention of long-term [10-year] mortality,” they suggested.  

In an accompanying editorial, Usman Baber, MD, commented that this study provides a “novel insight.”

Specifically, while patients without HCLs had significantly lower 10-year mortality with CABG versus PCI (18.8% vs. 26.0%; P = .003), an opposite trend was observed among those with HCLs (39.0% vs. 34.0%; P = .26; P int = .005).

The patients with HCLs had higher SYNTAX scores (30.8 vs. 22.4; P < .001) and more complex CAD, so their lack of 10-year mortality benefit with CABG “is somewhat unexpected and warrants further scrutiny,” added Dr. Baber, from the University of Oklahoma Health Sciences Center in Oklahoma City.

Dr. Serruys and Dr. Kawashima agreed that “this study highlights the need for further research on this topic focusing on this specific population with HCLs,” which were 30% of the patients with complex lesions who participated in SYNTAXES.
 

Consider factors beyond coronary anatomy

The current findings reinforce “the importance of considering not just coronary anatomy, but patient age and other comorbid factors when evaluating mode of revascularization,” said Dr. Baber.

“Coronary calcification is a strong factor in deciding between CABG versus PCI, as multiple studies have shown that CAC increases risk after PCI, even with contemporary safe stent platforms,” he explained in an email.

The current study suggests the adverse prognosis associated with CAC also persists for patients treated with CABG.

Dr. Baber said that, “for patients in whom PCI may not be feasible due to extensive and bulky coronary calcification, it is important to emphasize that the benefits of CABG (versus PCI) may not be as significant or durable.”

“The lack of benefit with CABG,” he added, “is likely due to comorbid factors that tend to increase in prevalence with vascular calcification (older age, peripheral arterial disease, renal impairment, etc).”

This study reinforces “the importance of not just considering coronary complexity, but also additional noncoronary factors that influence long-term prognosis in patients with advanced multivessel CAD,” Dr. Baber stressed.

More aggressive lipid-lowering or antithrombotic therapy may improve the prognosis for such patients, he suggested.

“In general,” Dr. Serruys and Dr. Kawashima similarly noted, “for short-/mid-term outcomes, CABG is preferred to PCI in patients with HCLs because of a higher rate of complete revascularization and less need for repeat revascularization.”

“Our findings at 10 years are in line with the general findings preferring CABG in mid and long term, whereas the benefit of very long-term follow-up might be more complex to capture and comprehend,” they concluded. “Whether HCLs require special consideration when deciding the mode of revascularization beyond their contribution to the SYNTAX score deserves further evaluation.

“Newer PCI technology or CABG methods may become a game-changer in the future,” they speculated.
 

Worse clinical outcomes

Heavy coronary calcification is associated with worse clinical outcomes after PCI or CABG, but to date, no trial has compared 10-year outcomes after PCI or CABG in patients with complex CAD with versus without HCLs.

To look at this, Dr. Kawashima and colleagues performed a subanalysis of patients in the SYNTAXES study. The original SYNTAX trial had randomized 1,800 patients with complex CAD who were eligible for either PCI or CABG 1:1 to these two treatments, with a 5-year follow-up, and SYNTAXES extended the follow-up to 10 years.  

Of the 1,800 patients, 532 (29.6%) had at least one HCL and the rest (70.4%) did not.

The median follow-up in SYNTAXES was 11.2 years overall and 11.9 years in survivors.

At baseline, compared with other patients, those with HCLs were older and had a lower body mass index and higher rates of insulin-treated diabetes, hypertension, previous cerebrovascular disease, peripheral vascular disease, chronic obstructive pulmonary disease, chronic kidney disease, and heart failure.

After adjusting for multiple variables, having a HCL was an independent predictor of greater risk of 10-year mortality (hazard ratio, 1.36; 95% confidence interval, 1.09-1.69; P = .006).

In patients without HCLs, mortality was significantly higher after PCI than CABG (HR, 1.44; 95% CI, 1.14-1.83; P = .003), whereas in those with HCLs, there was no significant difference (HR, 0.85; 95% CI, 0.64-1.13; P = .264).

The location of the HCL did not have any impact on 10-year mortality regardless of the assigned treatment.

Among patients with at least one HCL who underwent CABG, those with at least two HCLs had greater 10-year all-cause mortality than those with one HCL; this difference was not seen among patients with at least one HCL who underwent PCI.

The researchers acknowledge study limitations include that it was a post hoc analysis, so it should be considered hypothesis generating.

In addition, SYNTAX was conducted between 2005 and 2007, when PCI mainly used first-generation paclitaxel drug-eluting stents, so the findings may not be generalizable to current practice.

SYNTAXES was supported by the German Foundation of Heart Research. SYNTAX, during 0- to 5-year follow-up, was funded by Boston Scientific. Dr. Serruys reported receiving personal fees from SMT, Philips/Volcano, Xeltis, Novartis, and Meril Life. Dr. Kawashima reported no relevant financial relationships. Dr. Baber reported receiving honoraria and speaker fees from AstraZeneca, Biotronik, and Amgen.

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

Patients with complex coronary artery disease (CAD) – either three-vessel disease and/or left main disease – who also had heavy coronary artery calcification (CAC) had greater all-cause mortality 10 years after revascularization, compared with those without such lesions.

However, perhaps unexpectedly, patients with heavily calcified lesions (HCLs) had similar 10-year survival whether they had undergone coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI).

These findings from a post hoc analysis of the SYNTAX Extended Survival (SYNTAXES) study led by Hideyuki Kawashima, MD, PhD, National University of Ireland, Galway, and the University of Amsterdam, were published online Dec. 29, 2021, in JACC: Cardiovascular Interventions.

“There was an apparent lack of benefit at very long-term with CABG versus PCI in the presence of HCL,” Dr. Kawashima and corresponding author Patrick W. Serruys, MD, PhD, National University of Ireland and Imperial College London, summarized in a joint email to this news organization.

“Since HCLs – the final status of atherosclerosis and inflammation – reflect the aging process, complexity, and extensiveness of CAD, and comorbidity, it is possible that the currently available revascularization methods do not provide benefit in the prevention of long-term [10-year] mortality,” they suggested.  

In an accompanying editorial, Usman Baber, MD, commented that this study provides a “novel insight.”

Specifically, while patients without HCLs had significantly lower 10-year mortality with CABG versus PCI (18.8% vs. 26.0%; P = .003), an opposite trend was observed among those with HCLs (39.0% vs. 34.0%; P = .26; P int = .005).

The patients with HCLs had higher SYNTAX scores (30.8 vs. 22.4; P < .001) and more complex CAD, so their lack of 10-year mortality benefit with CABG “is somewhat unexpected and warrants further scrutiny,” added Dr. Baber, from the University of Oklahoma Health Sciences Center in Oklahoma City.

Dr. Serruys and Dr. Kawashima agreed that “this study highlights the need for further research on this topic focusing on this specific population with HCLs,” which were 30% of the patients with complex lesions who participated in SYNTAXES.
 

Consider factors beyond coronary anatomy

The current findings reinforce “the importance of considering not just coronary anatomy, but patient age and other comorbid factors when evaluating mode of revascularization,” said Dr. Baber.

“Coronary calcification is a strong factor in deciding between CABG versus PCI, as multiple studies have shown that CAC increases risk after PCI, even with contemporary safe stent platforms,” he explained in an email.

The current study suggests the adverse prognosis associated with CAC also persists for patients treated with CABG.

Dr. Baber said that, “for patients in whom PCI may not be feasible due to extensive and bulky coronary calcification, it is important to emphasize that the benefits of CABG (versus PCI) may not be as significant or durable.”

“The lack of benefit with CABG,” he added, “is likely due to comorbid factors that tend to increase in prevalence with vascular calcification (older age, peripheral arterial disease, renal impairment, etc).”

This study reinforces “the importance of not just considering coronary complexity, but also additional noncoronary factors that influence long-term prognosis in patients with advanced multivessel CAD,” Dr. Baber stressed.

More aggressive lipid-lowering or antithrombotic therapy may improve the prognosis for such patients, he suggested.

“In general,” Dr. Serruys and Dr. Kawashima similarly noted, “for short-/mid-term outcomes, CABG is preferred to PCI in patients with HCLs because of a higher rate of complete revascularization and less need for repeat revascularization.”

“Our findings at 10 years are in line with the general findings preferring CABG in mid and long term, whereas the benefit of very long-term follow-up might be more complex to capture and comprehend,” they concluded. “Whether HCLs require special consideration when deciding the mode of revascularization beyond their contribution to the SYNTAX score deserves further evaluation.

“Newer PCI technology or CABG methods may become a game-changer in the future,” they speculated.
 

Worse clinical outcomes

Heavy coronary calcification is associated with worse clinical outcomes after PCI or CABG, but to date, no trial has compared 10-year outcomes after PCI or CABG in patients with complex CAD with versus without HCLs.

To look at this, Dr. Kawashima and colleagues performed a subanalysis of patients in the SYNTAXES study. The original SYNTAX trial had randomized 1,800 patients with complex CAD who were eligible for either PCI or CABG 1:1 to these two treatments, with a 5-year follow-up, and SYNTAXES extended the follow-up to 10 years.  

Of the 1,800 patients, 532 (29.6%) had at least one HCL and the rest (70.4%) did not.

The median follow-up in SYNTAXES was 11.2 years overall and 11.9 years in survivors.

At baseline, compared with other patients, those with HCLs were older and had a lower body mass index and higher rates of insulin-treated diabetes, hypertension, previous cerebrovascular disease, peripheral vascular disease, chronic obstructive pulmonary disease, chronic kidney disease, and heart failure.

After adjusting for multiple variables, having a HCL was an independent predictor of greater risk of 10-year mortality (hazard ratio, 1.36; 95% confidence interval, 1.09-1.69; P = .006).

In patients without HCLs, mortality was significantly higher after PCI than CABG (HR, 1.44; 95% CI, 1.14-1.83; P = .003), whereas in those with HCLs, there was no significant difference (HR, 0.85; 95% CI, 0.64-1.13; P = .264).

The location of the HCL did not have any impact on 10-year mortality regardless of the assigned treatment.

Among patients with at least one HCL who underwent CABG, those with at least two HCLs had greater 10-year all-cause mortality than those with one HCL; this difference was not seen among patients with at least one HCL who underwent PCI.

The researchers acknowledge study limitations include that it was a post hoc analysis, so it should be considered hypothesis generating.

In addition, SYNTAX was conducted between 2005 and 2007, when PCI mainly used first-generation paclitaxel drug-eluting stents, so the findings may not be generalizable to current practice.

SYNTAXES was supported by the German Foundation of Heart Research. SYNTAX, during 0- to 5-year follow-up, was funded by Boston Scientific. Dr. Serruys reported receiving personal fees from SMT, Philips/Volcano, Xeltis, Novartis, and Meril Life. Dr. Kawashima reported no relevant financial relationships. Dr. Baber reported receiving honoraria and speaker fees from AstraZeneca, Biotronik, and Amgen.

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

Patients with complex coronary artery disease (CAD) – either three-vessel disease and/or left main disease – who also had heavy coronary artery calcification (CAC) had greater all-cause mortality 10 years after revascularization, compared with those without such lesions.

However, perhaps unexpectedly, patients with heavily calcified lesions (HCLs) had similar 10-year survival whether they had undergone coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI).

These findings from a post hoc analysis of the SYNTAX Extended Survival (SYNTAXES) study led by Hideyuki Kawashima, MD, PhD, National University of Ireland, Galway, and the University of Amsterdam, were published online Dec. 29, 2021, in JACC: Cardiovascular Interventions.

“There was an apparent lack of benefit at very long-term with CABG versus PCI in the presence of HCL,” Dr. Kawashima and corresponding author Patrick W. Serruys, MD, PhD, National University of Ireland and Imperial College London, summarized in a joint email to this news organization.

“Since HCLs – the final status of atherosclerosis and inflammation – reflect the aging process, complexity, and extensiveness of CAD, and comorbidity, it is possible that the currently available revascularization methods do not provide benefit in the prevention of long-term [10-year] mortality,” they suggested.  

In an accompanying editorial, Usman Baber, MD, commented that this study provides a “novel insight.”

Specifically, while patients without HCLs had significantly lower 10-year mortality with CABG versus PCI (18.8% vs. 26.0%; P = .003), an opposite trend was observed among those with HCLs (39.0% vs. 34.0%; P = .26; P int = .005).

The patients with HCLs had higher SYNTAX scores (30.8 vs. 22.4; P < .001) and more complex CAD, so their lack of 10-year mortality benefit with CABG “is somewhat unexpected and warrants further scrutiny,” added Dr. Baber, from the University of Oklahoma Health Sciences Center in Oklahoma City.

Dr. Serruys and Dr. Kawashima agreed that “this study highlights the need for further research on this topic focusing on this specific population with HCLs,” which were 30% of the patients with complex lesions who participated in SYNTAXES.
 

Consider factors beyond coronary anatomy

The current findings reinforce “the importance of considering not just coronary anatomy, but patient age and other comorbid factors when evaluating mode of revascularization,” said Dr. Baber.

“Coronary calcification is a strong factor in deciding between CABG versus PCI, as multiple studies have shown that CAC increases risk after PCI, even with contemporary safe stent platforms,” he explained in an email.

The current study suggests the adverse prognosis associated with CAC also persists for patients treated with CABG.

Dr. Baber said that, “for patients in whom PCI may not be feasible due to extensive and bulky coronary calcification, it is important to emphasize that the benefits of CABG (versus PCI) may not be as significant or durable.”

“The lack of benefit with CABG,” he added, “is likely due to comorbid factors that tend to increase in prevalence with vascular calcification (older age, peripheral arterial disease, renal impairment, etc).”

This study reinforces “the importance of not just considering coronary complexity, but also additional noncoronary factors that influence long-term prognosis in patients with advanced multivessel CAD,” Dr. Baber stressed.

More aggressive lipid-lowering or antithrombotic therapy may improve the prognosis for such patients, he suggested.

“In general,” Dr. Serruys and Dr. Kawashima similarly noted, “for short-/mid-term outcomes, CABG is preferred to PCI in patients with HCLs because of a higher rate of complete revascularization and less need for repeat revascularization.”

“Our findings at 10 years are in line with the general findings preferring CABG in mid and long term, whereas the benefit of very long-term follow-up might be more complex to capture and comprehend,” they concluded. “Whether HCLs require special consideration when deciding the mode of revascularization beyond their contribution to the SYNTAX score deserves further evaluation.

“Newer PCI technology or CABG methods may become a game-changer in the future,” they speculated.
 

Worse clinical outcomes

Heavy coronary calcification is associated with worse clinical outcomes after PCI or CABG, but to date, no trial has compared 10-year outcomes after PCI or CABG in patients with complex CAD with versus without HCLs.

To look at this, Dr. Kawashima and colleagues performed a subanalysis of patients in the SYNTAXES study. The original SYNTAX trial had randomized 1,800 patients with complex CAD who were eligible for either PCI or CABG 1:1 to these two treatments, with a 5-year follow-up, and SYNTAXES extended the follow-up to 10 years.  

Of the 1,800 patients, 532 (29.6%) had at least one HCL and the rest (70.4%) did not.

The median follow-up in SYNTAXES was 11.2 years overall and 11.9 years in survivors.

At baseline, compared with other patients, those with HCLs were older and had a lower body mass index and higher rates of insulin-treated diabetes, hypertension, previous cerebrovascular disease, peripheral vascular disease, chronic obstructive pulmonary disease, chronic kidney disease, and heart failure.

After adjusting for multiple variables, having a HCL was an independent predictor of greater risk of 10-year mortality (hazard ratio, 1.36; 95% confidence interval, 1.09-1.69; P = .006).

In patients without HCLs, mortality was significantly higher after PCI than CABG (HR, 1.44; 95% CI, 1.14-1.83; P = .003), whereas in those with HCLs, there was no significant difference (HR, 0.85; 95% CI, 0.64-1.13; P = .264).

The location of the HCL did not have any impact on 10-year mortality regardless of the assigned treatment.

Among patients with at least one HCL who underwent CABG, those with at least two HCLs had greater 10-year all-cause mortality than those with one HCL; this difference was not seen among patients with at least one HCL who underwent PCI.

The researchers acknowledge study limitations include that it was a post hoc analysis, so it should be considered hypothesis generating.

In addition, SYNTAX was conducted between 2005 and 2007, when PCI mainly used first-generation paclitaxel drug-eluting stents, so the findings may not be generalizable to current practice.

SYNTAXES was supported by the German Foundation of Heart Research. SYNTAX, during 0- to 5-year follow-up, was funded by Boston Scientific. Dr. Serruys reported receiving personal fees from SMT, Philips/Volcano, Xeltis, Novartis, and Meril Life. Dr. Kawashima reported no relevant financial relationships. Dr. Baber reported receiving honoraria and speaker fees from AstraZeneca, Biotronik, and Amgen.

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

This transcript has been edited for clarity. The transcript and an accompanying video first appeared on Medscape.com.

Justin L. Berk, MD, MPH, MBA: Welcome back to The Cribsiders, our video recap of our pediatric medicine podcast. We interview leading experts in the field to bring clinical pearls and practice-changing knowledge, and answer lingering questions about core topics in pediatric medicine. Chris, what is our topic today?

Christopher J. Chiu, MD: I was really happy to be able to talk about our recent episode with Dr. Carissa Baker-Smith, a pediatric cardiologist and director of the Nemours preventive cardiology program. She helped us review the pediatric screening guidelines for blood pressure, including initial workup and treatment.

Dr. Berk: This was a really great episode that a lot of people found really helpful. What were some of the key takeaway pearls that you think listeners would be interested in?

Dr. Chiu: We talked about when and how we should be checking blood pressures in children. Blood pressure should be checked at every well-child visit starting at age 3. But if they have other risk factors like kidney disease or a condition such as coarctation of the aorta, then blood pressure should be checked at every visit.

Dr. Berk: One thing she spoke about was how blood pressures should be measured. How should we be checking blood pressures in the clinic?

Dr. Chiu: Clinic blood pressures are usually checked with oscillometric devices. They can differ by manufacturer, but basically they find a mean arterial pressure and then each device has a method of calculating systolic and diastolic pressures. Now after that, if the child’s blood pressure is maybe abnormal, you want to double-check a manual blood pressure using Korotkoff sounds to confirm the blood pressure.

She reminded us that blood pressure should be measured with the child sitting with their back supported, feet flat on the floor, and arm at the level of the heart. Make sure you use the right size cuff. The bladder of the cuff should be 40% of the width of the arm, and about 80%-100% of the arm circumference. She recommends sizing up if you have to.

Dr. Berk: Accuracy of blood pressure management was a really important point, especially for diagnosis at this stage. Can you walk us through what we learned about diagnosis of hypertension?

Dr. Chiu: The definitions of hypertension come from the Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents. Up until the age of 13, they define prehypertension as systolic and diastolic blood pressures between the 90th and 95th percentile, or if the blood pressure exceeds 120/80 mm Hg. Hypertension is defined when blood pressure reaches the 95th percentile. Now age 13 is when it gets a little hazy. Many changes in the guidelines happen at age 13, when hypertension starts being defined by adult guidelines. The 2017 adult hypertension guidelines define stage 1 hypertension as 130/89 to 139/89, and stage 2 hypertension as greater than 140/90.

Dr. Berk: How about workup of hypertension? The work of pediatric hypertension is always a little bit complex. What are some of the pearls you took away?

Dr. Chui: She talked about tailoring the workup to the child. So when we’re doing our workup, obviously physical exam should be the first thing we do. You have to assess and compare pulses, which is one of the most important parts of the initial evaluation. Obviously, looking at coarctation of the aorta, but also looking for things like a cushingoid appearance. If the child is less than 6 years of age, she recommends a referral to nephrology for more comprehensive renovascular workup, which probably will include renal ultrasound, urinalysis, metabolic panel, and thyroid studies.

We have to be cognizant of secondary causes of hypertension, such as endocrine tumors, hyperthyroidism, aortic disease, or even medication-induced hypertension. She told us that in the majority of these cases, especially with our obese older children, primary hypertension or essential hypertension is the most likely cause.

Dr. Berk: That was my big takeaway. If they’re really young, they need a big workup, but otherwise it is likely primary hypertension. What did we learn about treatment?

Dr. Chui: Just as we tailor our assessment to the child, we also have to tailor treatment. We know that lifestyle modification is usually the first line of treatment, especially for primary hypertension, and Dr. Baker-Smith tells us that we really need to perform counseling that meets the patient where they are. So if they like dancing to the newest TikTok trends or music videos, maybe we can encourage them to move more that way. Using our motivational interviewing skills is really key here.

If you want to start medication, Dr. Baker-Smith uses things like low-dose ACE inhibitors or calcium channel blockers, but obviously it’ll be tailored to the patient and any underlying conditions.

Dr. Berk: That’s great – a lot of wonderful pearls on the diagnosis and management of pediatric hypertension. Thank you for joining us for another video recap of The Cribsiders pediatric podcast. You can download the full podcast, Off the Cuff: Managing Pediatric Hypertension in Your Primary Care Clinic, on any podcast player, or check out our website at www.theCribsiders.com.

Christopher J. Chiu, MD, is assistant professor, department of internal medicine, division of general internal medicine, Ohio State University, Columbus; lead physician, general internal medicine, OSU Outpatient Care East; department of internal medicine, division of general internal medicine, Ohio State University Wexner Medical Center. Dr. Chiu has disclosed no relevant financial relationships. Justin L. Berk, MD, MPH, MBA, is assistant professor, department of medicine; assistant professor, department of pediatrics, Brown University, Providence, R.I.

This transcript has been edited for clarity. The transcript and an accompanying video first appeared on Medscape.com.

Justin L. Berk, MD, MPH, MBA: Welcome back to The Cribsiders, our video recap of our pediatric medicine podcast. We interview leading experts in the field to bring clinical pearls and practice-changing knowledge, and answer lingering questions about core topics in pediatric medicine. Chris, what is our topic today?

Christopher J. Chiu, MD: I was really happy to be able to talk about our recent episode with Dr. Carissa Baker-Smith, a pediatric cardiologist and director of the Nemours preventive cardiology program. She helped us review the pediatric screening guidelines for blood pressure, including initial workup and treatment.

Dr. Berk: This was a really great episode that a lot of people found really helpful. What were some of the key takeaway pearls that you think listeners would be interested in?

Dr. Chiu: We talked about when and how we should be checking blood pressures in children. Blood pressure should be checked at every well-child visit starting at age 3. But if they have other risk factors like kidney disease or a condition such as coarctation of the aorta, then blood pressure should be checked at every visit.

Dr. Berk: One thing she spoke about was how blood pressures should be measured. How should we be checking blood pressures in the clinic?

Dr. Chiu: Clinic blood pressures are usually checked with oscillometric devices. They can differ by manufacturer, but basically they find a mean arterial pressure and then each device has a method of calculating systolic and diastolic pressures. Now after that, if the child’s blood pressure is maybe abnormal, you want to double-check a manual blood pressure using Korotkoff sounds to confirm the blood pressure.

She reminded us that blood pressure should be measured with the child sitting with their back supported, feet flat on the floor, and arm at the level of the heart. Make sure you use the right size cuff. The bladder of the cuff should be 40% of the width of the arm, and about 80%-100% of the arm circumference. She recommends sizing up if you have to.

Dr. Berk: Accuracy of blood pressure management was a really important point, especially for diagnosis at this stage. Can you walk us through what we learned about diagnosis of hypertension?

Dr. Chiu: The definitions of hypertension come from the Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents. Up until the age of 13, they define prehypertension as systolic and diastolic blood pressures between the 90th and 95th percentile, or if the blood pressure exceeds 120/80 mm Hg. Hypertension is defined when blood pressure reaches the 95th percentile. Now age 13 is when it gets a little hazy. Many changes in the guidelines happen at age 13, when hypertension starts being defined by adult guidelines. The 2017 adult hypertension guidelines define stage 1 hypertension as 130/89 to 139/89, and stage 2 hypertension as greater than 140/90.

Dr. Berk: How about workup of hypertension? The work of pediatric hypertension is always a little bit complex. What are some of the pearls you took away?

Dr. Chui: She talked about tailoring the workup to the child. So when we’re doing our workup, obviously physical exam should be the first thing we do. You have to assess and compare pulses, which is one of the most important parts of the initial evaluation. Obviously, looking at coarctation of the aorta, but also looking for things like a cushingoid appearance. If the child is less than 6 years of age, she recommends a referral to nephrology for more comprehensive renovascular workup, which probably will include renal ultrasound, urinalysis, metabolic panel, and thyroid studies.

We have to be cognizant of secondary causes of hypertension, such as endocrine tumors, hyperthyroidism, aortic disease, or even medication-induced hypertension. She told us that in the majority of these cases, especially with our obese older children, primary hypertension or essential hypertension is the most likely cause.

Dr. Berk: That was my big takeaway. If they’re really young, they need a big workup, but otherwise it is likely primary hypertension. What did we learn about treatment?

Dr. Chui: Just as we tailor our assessment to the child, we also have to tailor treatment. We know that lifestyle modification is usually the first line of treatment, especially for primary hypertension, and Dr. Baker-Smith tells us that we really need to perform counseling that meets the patient where they are. So if they like dancing to the newest TikTok trends or music videos, maybe we can encourage them to move more that way. Using our motivational interviewing skills is really key here.

If you want to start medication, Dr. Baker-Smith uses things like low-dose ACE inhibitors or calcium channel blockers, but obviously it’ll be tailored to the patient and any underlying conditions.

Dr. Berk: That’s great – a lot of wonderful pearls on the diagnosis and management of pediatric hypertension. Thank you for joining us for another video recap of The Cribsiders pediatric podcast. You can download the full podcast, Off the Cuff: Managing Pediatric Hypertension in Your Primary Care Clinic, on any podcast player, or check out our website at www.theCribsiders.com.

Christopher J. Chiu, MD, is assistant professor, department of internal medicine, division of general internal medicine, Ohio State University, Columbus; lead physician, general internal medicine, OSU Outpatient Care East; department of internal medicine, division of general internal medicine, Ohio State University Wexner Medical Center. Dr. Chiu has disclosed no relevant financial relationships. Justin L. Berk, MD, MPH, MBA, is assistant professor, department of medicine; assistant professor, department of pediatrics, Brown University, Providence, R.I.

This transcript has been edited for clarity. The transcript and an accompanying video first appeared on Medscape.com.

Justin L. Berk, MD, MPH, MBA: Welcome back to The Cribsiders, our video recap of our pediatric medicine podcast. We interview leading experts in the field to bring clinical pearls and practice-changing knowledge, and answer lingering questions about core topics in pediatric medicine. Chris, what is our topic today?

Christopher J. Chiu, MD: I was really happy to be able to talk about our recent episode with Dr. Carissa Baker-Smith, a pediatric cardiologist and director of the Nemours preventive cardiology program. She helped us review the pediatric screening guidelines for blood pressure, including initial workup and treatment.

Dr. Berk: This was a really great episode that a lot of people found really helpful. What were some of the key takeaway pearls that you think listeners would be interested in?

Dr. Chiu: We talked about when and how we should be checking blood pressures in children. Blood pressure should be checked at every well-child visit starting at age 3. But if they have other risk factors like kidney disease or a condition such as coarctation of the aorta, then blood pressure should be checked at every visit.

Dr. Berk: One thing she spoke about was how blood pressures should be measured. How should we be checking blood pressures in the clinic?

Dr. Chiu: Clinic blood pressures are usually checked with oscillometric devices. They can differ by manufacturer, but basically they find a mean arterial pressure and then each device has a method of calculating systolic and diastolic pressures. Now after that, if the child’s blood pressure is maybe abnormal, you want to double-check a manual blood pressure using Korotkoff sounds to confirm the blood pressure.

She reminded us that blood pressure should be measured with the child sitting with their back supported, feet flat on the floor, and arm at the level of the heart. Make sure you use the right size cuff. The bladder of the cuff should be 40% of the width of the arm, and about 80%-100% of the arm circumference. She recommends sizing up if you have to.

Dr. Berk: Accuracy of blood pressure management was a really important point, especially for diagnosis at this stage. Can you walk us through what we learned about diagnosis of hypertension?

Dr. Chiu: The definitions of hypertension come from the Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents. Up until the age of 13, they define prehypertension as systolic and diastolic blood pressures between the 90th and 95th percentile, or if the blood pressure exceeds 120/80 mm Hg. Hypertension is defined when blood pressure reaches the 95th percentile. Now age 13 is when it gets a little hazy. Many changes in the guidelines happen at age 13, when hypertension starts being defined by adult guidelines. The 2017 adult hypertension guidelines define stage 1 hypertension as 130/89 to 139/89, and stage 2 hypertension as greater than 140/90.

Dr. Berk: How about workup of hypertension? The work of pediatric hypertension is always a little bit complex. What are some of the pearls you took away?

Dr. Chui: She talked about tailoring the workup to the child. So when we’re doing our workup, obviously physical exam should be the first thing we do. You have to assess and compare pulses, which is one of the most important parts of the initial evaluation. Obviously, looking at coarctation of the aorta, but also looking for things like a cushingoid appearance. If the child is less than 6 years of age, she recommends a referral to nephrology for more comprehensive renovascular workup, which probably will include renal ultrasound, urinalysis, metabolic panel, and thyroid studies.

We have to be cognizant of secondary causes of hypertension, such as endocrine tumors, hyperthyroidism, aortic disease, or even medication-induced hypertension. She told us that in the majority of these cases, especially with our obese older children, primary hypertension or essential hypertension is the most likely cause.

Dr. Berk: That was my big takeaway. If they’re really young, they need a big workup, but otherwise it is likely primary hypertension. What did we learn about treatment?

Dr. Chui: Just as we tailor our assessment to the child, we also have to tailor treatment. We know that lifestyle modification is usually the first line of treatment, especially for primary hypertension, and Dr. Baker-Smith tells us that we really need to perform counseling that meets the patient where they are. So if they like dancing to the newest TikTok trends or music videos, maybe we can encourage them to move more that way. Using our motivational interviewing skills is really key here.

If you want to start medication, Dr. Baker-Smith uses things like low-dose ACE inhibitors or calcium channel blockers, but obviously it’ll be tailored to the patient and any underlying conditions.

Dr. Berk: That’s great – a lot of wonderful pearls on the diagnosis and management of pediatric hypertension. Thank you for joining us for another video recap of The Cribsiders pediatric podcast. You can download the full podcast, Off the Cuff: Managing Pediatric Hypertension in Your Primary Care Clinic, on any podcast player, or check out our website at www.theCribsiders.com.

Christopher J. Chiu, MD, is assistant professor, department of internal medicine, division of general internal medicine, Ohio State University, Columbus; lead physician, general internal medicine, OSU Outpatient Care East; department of internal medicine, division of general internal medicine, Ohio State University Wexner Medical Center. Dr. Chiu has disclosed no relevant financial relationships. Justin L. Berk, MD, MPH, MBA, is assistant professor, department of medicine; assistant professor, department of pediatrics, Brown University, Providence, R.I.

Chest pain is one of the most common concerns in patients presenting to the emergency department in the United States, accounting for approximately 7.6 million visits annually.¹ Given the high mortality rate associated with acute coronary syndromes, prompt evaluation of chest pain is essential.² Even in mild cases, recognition of newly onset or worsening coronary artery disease (CAD) is crucial to ensure that patients receive optimal medication therapy.

In symptomatic patients with risk factors for CAD, such as advanced age, hypertension, hyperlipidemia, obesity, and diabetes mellitus, myocardial perfusion imaging (MPI) is frequently used as a modality to assess the presence, location, and severity of ischemic or infarcted myocardium.² MPI requires administration of a radiopharmaceutical before and after the patient undergoes a form of stress.² This radiopharmaceutical is then detected in the myocardium with a nuclear camera, and images are obtained of the heart to assess myocardial blood flow.²

MPI can be performed using exercise-induced stress via a treadmill, or medication-induced stress (Table 1). In both strategies, healthy coronary arteries dilate to provide the myocardium with more blood flow to meet the increasing myocardial oxygen demand during this period of stress. While healthy vessels are able to dilate appropriately, coronary arteries with flow-limiting stenoses are unable to dilate to the same extent in response to stress.² Because radioactive isotope uptake by the myocardium is directly related to arterial blood flow, MPI is able to demonstrate a mismatch in coronary blood flow between healthy and diseased coronary arteries indicated by differences in radioisotope uptake.² The presence of such a mismatch, in conjunction with clinical history, potentially suggests the presence of CAD.

Because nicotine and nicotine replacement therapy (NRT) may have substantial effects on coronary circulation, a current area of controversy is whether these should be stopped prior to the use of a stress-inducing medication during MPI. To date, no formal drug interaction studies have been conducted between nicotine and regadenoson.⁵ Similarly, the ADVANCE MPI 2 Trial, which led to the US Food and Drug Administration approval of regadenoson, did not specify restrictions on the use of nicotine prior to stress testing in the protocol.⁶ However, as this trial was multicenter, investigators admit that individual study sites could have had their own restrictions on the use of nicotine prior to stress testing with regadenoson, but this information was not collected.⁶ The current review focuses on how the simultaneous use of nicotine or NRT during MPI with pharmacologic agents, such as regadenoson, may affect the accuracy of imaging results and the clinical impact of this interaction.

Nicotine Coronary Artery Effect

It is well documented that long-term cigarette smoking is a major risk factor for CAD.⁷ Compared with nonsmokers, cigarette smokers experience 2 times greater risk of morbidity and mortality from ischemic heart disease.⁷ There are several mechanisms by which nicotine induces damage to the myocardium (Figure). Nicotine has direct effects on both the sympathetic nervous system (SNS) and myocardial endothelium.⁸ Together, these factors result in reduced coronary blood flow, leading to less oxygen supply to meet an increased oxygen demand, resulting in myocardial ischemia.

Nicotine’s effect on coronary vasomotor tone occurs primarily through noradrenergic stimulation of α and β receptors associated with coronary vasoconstriction or vasodilation, respectively.^9,10 These competing influences on coronary blood flow appear to manifest differently based on whether patients are at rest or in a stressed state. A study by Czerin and colleagues demonstrated that in healthy patients with relatively short smoking histories and in a healthy nonsmoker control group, coronary blood flow increased by 25% and 40%, respectively, with nicotine use at rest.⁹ However, when these patients were stressed with dipyramidole and while smoking during the examination, myocardial blood flow was reduced by 11% in the study group and 14% in the control group.⁹ This is likely because the patients studied had relatively healthy coronary arteries that were able to maximally dilate when stressed. In this scenario, nicotine’s dilatory effects are offset by nicotine’s α-receptor–mediated vasoconstriction effects.⁹ Of note, patients in the study group experienced a somewhat diminished increase in coronary blood flow at rest with nicotine use, suggesting that even a short smoking history may damage the myocardial endothelium, rendering it less responsive to nicotine’s vasodilatory effects.⁹

Nicotine Replacement Therapy and Stress Testing

Given the association between cigarette smoking and CAD, medical practitioners strongly encourage patients to quit smoking to reduce their risk of adverse cardiovascular outcomes. Various smoking cessation treatments are available for patients. Common, readily accessible forms of therapy include nicotine replacement products (Table 2).

Early studies of NRT in patients with underlying CVD found an increased risk of cardiovascular events, such as myocardial infarction, presumably due to the nicotine content of these products.^13,14 However, the concentration of nicotine in NRT is substantially lower than that found in cigarettes and in some formulations, such as transdermal patches, nicotine is delivered over a prolonged period of time.¹⁵ For this reason, NRT is thought to be safe in patients with underlying CVD and stable ischemic heart disease. A recent systematic review and meta-analysis found that while NRT may be associated with tachycardia, it did not increase the risk of more serious cardiovascular adverse effects (AEs).^16,17

Given the lower nicotine concentration in NRT products, the associated hemodynamic effect of nicotine also is thought to be less pronounced. In a study conducted by Tzivoni and colleagues in patients with CAD using transdermal nicotine patches, no differences in blood pressure, heart rate, ischemia, or arrhythmias were found from baseline to 2 weeks.¹⁸ These findings were further confirmed in a small study by Lucini and colleagues, which found that nicotine patches produced slight hemodynamic effects, but to a lesser extent than cigarette smoking.¹⁹ For the NRT gum formulation, while a small study found that 4 mg produced coronary vasoconstriction in patients with underlying CAD, a study by Nitenberg and Antony demonstrated that healthy and diseased coronary arteries did not significantly constrict while patients were using nicotine gum both before and after a cold pressor test, suggesting a lesser degree of coronary vasoconstriction than nicotine from cigarette smoking.^20,21 Similar findings have been described with the nicotine intranasal spray in a study by Keeley and colleagues, which showed no additional AEs on myocardial demand or vasoconstriction when an intranasal nicotine spray was added to cigarette smoking.²² Importantly, a review of the transdermal and gum formulations found that these less pronounced hemodynamic effects were observed across different doses of NRT; however, further studies are needed to clarify the relationship between NRT dose and cardiovascular effects.²³

Overall, NRT does not seem to activate the SNS to the same degree as nicotine obtained via cigarette smoking and likely does not increase the myocardial oxygen demand as much. Additionally, by containing a lower concentration of nicotine, NRT may not impair the myocardium’s ability to supply oxygen to coronary arteries to the same extent as nicotine from cigarette smoking. Therefore, the effects of NRT on MPI using a stress-inducing medication may not be as pronounced. However, due to study limitations, results should be interpreted cautiously.^18-23

Conclusions

Because of the close relationship between cigarette smoking and CAD, many patients with underlying CVD are either current smokers or may be using NRT for smoking cessation. Therefore, the question of whether to refrain from nicotine use prior to MPI is clinically relevant. Currently, there is a lack of high-quality studies demonstrating the effects of nicotine and NRT on coronary perfusion. Because of this, the impact of nicotine and NRT use on the accuracy of MPI using stress-inducing medications remains uncertain. Nevertheless, given that nicotine and NRT may largely affect the accuracy of imaging results, several institutions have adopted protocols that prohibit patients from using these drugs on the day of nuclear stress testing.

There are currently no data specifying the number of hours to hold nicotine products prior to cardiac stress testing. It is generally recommended that other medications that affect coronary blood flow be held for 5 half-lives before conducting MPI.⁴ Following the same guidance for nicotine and NRT may present a reasonable approach to ensure accurate imaging results. Based on the discussed literature, patients should be instructed to refrain from cigarette smoking for at least 5 to 10 hours prior to MPI, given nicotine’s half-life of about 1 to 2 hours.²⁴

The data for NRT are less clear. While use of NRT may not be an absolute contraindication to conducting MPI, it is important to consider that this may affect the accuracy of results. Given this uncertainty, it is likely ideal to hold NRT prior to MPI, based on the specific formulation of NRT and that product's half-life. Further robust studies are needed to analyze the impact of nicotine and NRT on the accuracy of nuclear stress testing using a medication.

Chest pain is one of the most common concerns in patients presenting to the emergency department in the United States, accounting for approximately 7.6 million visits annually.¹ Given the high mortality rate associated with acute coronary syndromes, prompt evaluation of chest pain is essential.² Even in mild cases, recognition of newly onset or worsening coronary artery disease (CAD) is crucial to ensure that patients receive optimal medication therapy.

In symptomatic patients with risk factors for CAD, such as advanced age, hypertension, hyperlipidemia, obesity, and diabetes mellitus, myocardial perfusion imaging (MPI) is frequently used as a modality to assess the presence, location, and severity of ischemic or infarcted myocardium.² MPI requires administration of a radiopharmaceutical before and after the patient undergoes a form of stress.² This radiopharmaceutical is then detected in the myocardium with a nuclear camera, and images are obtained of the heart to assess myocardial blood flow.²

MPI can be performed using exercise-induced stress via a treadmill, or medication-induced stress (Table 1). In both strategies, healthy coronary arteries dilate to provide the myocardium with more blood flow to meet the increasing myocardial oxygen demand during this period of stress. While healthy vessels are able to dilate appropriately, coronary arteries with flow-limiting stenoses are unable to dilate to the same extent in response to stress.² Because radioactive isotope uptake by the myocardium is directly related to arterial blood flow, MPI is able to demonstrate a mismatch in coronary blood flow between healthy and diseased coronary arteries indicated by differences in radioisotope uptake.² The presence of such a mismatch, in conjunction with clinical history, potentially suggests the presence of CAD.

Because nicotine and nicotine replacement therapy (NRT) may have substantial effects on coronary circulation, a current area of controversy is whether these should be stopped prior to the use of a stress-inducing medication during MPI. To date, no formal drug interaction studies have been conducted between nicotine and regadenoson.⁵ Similarly, the ADVANCE MPI 2 Trial, which led to the US Food and Drug Administration approval of regadenoson, did not specify restrictions on the use of nicotine prior to stress testing in the protocol.⁶ However, as this trial was multicenter, investigators admit that individual study sites could have had their own restrictions on the use of nicotine prior to stress testing with regadenoson, but this information was not collected.⁶ The current review focuses on how the simultaneous use of nicotine or NRT during MPI with pharmacologic agents, such as regadenoson, may affect the accuracy of imaging results and the clinical impact of this interaction.

Nicotine Coronary Artery Effect

It is well documented that long-term cigarette smoking is a major risk factor for CAD.⁷ Compared with nonsmokers, cigarette smokers experience 2 times greater risk of morbidity and mortality from ischemic heart disease.⁷ There are several mechanisms by which nicotine induces damage to the myocardium (Figure). Nicotine has direct effects on both the sympathetic nervous system (SNS) and myocardial endothelium.⁸ Together, these factors result in reduced coronary blood flow, leading to less oxygen supply to meet an increased oxygen demand, resulting in myocardial ischemia.

Nicotine’s effect on coronary vasomotor tone occurs primarily through noradrenergic stimulation of α and β receptors associated with coronary vasoconstriction or vasodilation, respectively.^9,10 These competing influences on coronary blood flow appear to manifest differently based on whether patients are at rest or in a stressed state. A study by Czerin and colleagues demonstrated that in healthy patients with relatively short smoking histories and in a healthy nonsmoker control group, coronary blood flow increased by 25% and 40%, respectively, with nicotine use at rest.⁹ However, when these patients were stressed with dipyramidole and while smoking during the examination, myocardial blood flow was reduced by 11% in the study group and 14% in the control group.⁹ This is likely because the patients studied had relatively healthy coronary arteries that were able to maximally dilate when stressed. In this scenario, nicotine’s dilatory effects are offset by nicotine’s α-receptor–mediated vasoconstriction effects.⁹ Of note, patients in the study group experienced a somewhat diminished increase in coronary blood flow at rest with nicotine use, suggesting that even a short smoking history may damage the myocardial endothelium, rendering it less responsive to nicotine’s vasodilatory effects.⁹

Nicotine Replacement Therapy and Stress Testing

Given the association between cigarette smoking and CAD, medical practitioners strongly encourage patients to quit smoking to reduce their risk of adverse cardiovascular outcomes. Various smoking cessation treatments are available for patients. Common, readily accessible forms of therapy include nicotine replacement products (Table 2).

Early studies of NRT in patients with underlying CVD found an increased risk of cardiovascular events, such as myocardial infarction, presumably due to the nicotine content of these products.^13,14 However, the concentration of nicotine in NRT is substantially lower than that found in cigarettes and in some formulations, such as transdermal patches, nicotine is delivered over a prolonged period of time.¹⁵ For this reason, NRT is thought to be safe in patients with underlying CVD and stable ischemic heart disease. A recent systematic review and meta-analysis found that while NRT may be associated with tachycardia, it did not increase the risk of more serious cardiovascular adverse effects (AEs).^16,17

Given the lower nicotine concentration in NRT products, the associated hemodynamic effect of nicotine also is thought to be less pronounced. In a study conducted by Tzivoni and colleagues in patients with CAD using transdermal nicotine patches, no differences in blood pressure, heart rate, ischemia, or arrhythmias were found from baseline to 2 weeks.¹⁸ These findings were further confirmed in a small study by Lucini and colleagues, which found that nicotine patches produced slight hemodynamic effects, but to a lesser extent than cigarette smoking.¹⁹ For the NRT gum formulation, while a small study found that 4 mg produced coronary vasoconstriction in patients with underlying CAD, a study by Nitenberg and Antony demonstrated that healthy and diseased coronary arteries did not significantly constrict while patients were using nicotine gum both before and after a cold pressor test, suggesting a lesser degree of coronary vasoconstriction than nicotine from cigarette smoking.^20,21 Similar findings have been described with the nicotine intranasal spray in a study by Keeley and colleagues, which showed no additional AEs on myocardial demand or vasoconstriction when an intranasal nicotine spray was added to cigarette smoking.²² Importantly, a review of the transdermal and gum formulations found that these less pronounced hemodynamic effects were observed across different doses of NRT; however, further studies are needed to clarify the relationship between NRT dose and cardiovascular effects.²³

Overall, NRT does not seem to activate the SNS to the same degree as nicotine obtained via cigarette smoking and likely does not increase the myocardial oxygen demand as much. Additionally, by containing a lower concentration of nicotine, NRT may not impair the myocardium’s ability to supply oxygen to coronary arteries to the same extent as nicotine from cigarette smoking. Therefore, the effects of NRT on MPI using a stress-inducing medication may not be as pronounced. However, due to study limitations, results should be interpreted cautiously.^18-23

Conclusions

Because of the close relationship between cigarette smoking and CAD, many patients with underlying CVD are either current smokers or may be using NRT for smoking cessation. Therefore, the question of whether to refrain from nicotine use prior to MPI is clinically relevant. Currently, there is a lack of high-quality studies demonstrating the effects of nicotine and NRT on coronary perfusion. Because of this, the impact of nicotine and NRT use on the accuracy of MPI using stress-inducing medications remains uncertain. Nevertheless, given that nicotine and NRT may largely affect the accuracy of imaging results, several institutions have adopted protocols that prohibit patients from using these drugs on the day of nuclear stress testing.

There are currently no data specifying the number of hours to hold nicotine products prior to cardiac stress testing. It is generally recommended that other medications that affect coronary blood flow be held for 5 half-lives before conducting MPI.⁴ Following the same guidance for nicotine and NRT may present a reasonable approach to ensure accurate imaging results. Based on the discussed literature, patients should be instructed to refrain from cigarette smoking for at least 5 to 10 hours prior to MPI, given nicotine’s half-life of about 1 to 2 hours.²⁴

The data for NRT are less clear. While use of NRT may not be an absolute contraindication to conducting MPI, it is important to consider that this may affect the accuracy of results. Given this uncertainty, it is likely ideal to hold NRT prior to MPI, based on the specific formulation of NRT and that product's half-life. Further robust studies are needed to analyze the impact of nicotine and NRT on the accuracy of nuclear stress testing using a medication.

Chest pain is one of the most common concerns in patients presenting to the emergency department in the United States, accounting for approximately 7.6 million visits annually.¹ Given the high mortality rate associated with acute coronary syndromes, prompt evaluation of chest pain is essential.² Even in mild cases, recognition of newly onset or worsening coronary artery disease (CAD) is crucial to ensure that patients receive optimal medication therapy.

In symptomatic patients with risk factors for CAD, such as advanced age, hypertension, hyperlipidemia, obesity, and diabetes mellitus, myocardial perfusion imaging (MPI) is frequently used as a modality to assess the presence, location, and severity of ischemic or infarcted myocardium.² MPI requires administration of a radiopharmaceutical before and after the patient undergoes a form of stress.² This radiopharmaceutical is then detected in the myocardium with a nuclear camera, and images are obtained of the heart to assess myocardial blood flow.²

MPI can be performed using exercise-induced stress via a treadmill, or medication-induced stress (Table 1). In both strategies, healthy coronary arteries dilate to provide the myocardium with more blood flow to meet the increasing myocardial oxygen demand during this period of stress. While healthy vessels are able to dilate appropriately, coronary arteries with flow-limiting stenoses are unable to dilate to the same extent in response to stress.² Because radioactive isotope uptake by the myocardium is directly related to arterial blood flow, MPI is able to demonstrate a mismatch in coronary blood flow between healthy and diseased coronary arteries indicated by differences in radioisotope uptake.² The presence of such a mismatch, in conjunction with clinical history, potentially suggests the presence of CAD.

Because nicotine and nicotine replacement therapy (NRT) may have substantial effects on coronary circulation, a current area of controversy is whether these should be stopped prior to the use of a stress-inducing medication during MPI. To date, no formal drug interaction studies have been conducted between nicotine and regadenoson.⁵ Similarly, the ADVANCE MPI 2 Trial, which led to the US Food and Drug Administration approval of regadenoson, did not specify restrictions on the use of nicotine prior to stress testing in the protocol.⁶ However, as this trial was multicenter, investigators admit that individual study sites could have had their own restrictions on the use of nicotine prior to stress testing with regadenoson, but this information was not collected.⁶ The current review focuses on how the simultaneous use of nicotine or NRT during MPI with pharmacologic agents, such as regadenoson, may affect the accuracy of imaging results and the clinical impact of this interaction.

Nicotine Coronary Artery Effect

It is well documented that long-term cigarette smoking is a major risk factor for CAD.⁷ Compared with nonsmokers, cigarette smokers experience 2 times greater risk of morbidity and mortality from ischemic heart disease.⁷ There are several mechanisms by which nicotine induces damage to the myocardium (Figure). Nicotine has direct effects on both the sympathetic nervous system (SNS) and myocardial endothelium.⁸ Together, these factors result in reduced coronary blood flow, leading to less oxygen supply to meet an increased oxygen demand, resulting in myocardial ischemia.

Nicotine’s effect on coronary vasomotor tone occurs primarily through noradrenergic stimulation of α and β receptors associated with coronary vasoconstriction or vasodilation, respectively.^9,10 These competing influences on coronary blood flow appear to manifest differently based on whether patients are at rest or in a stressed state. A study by Czerin and colleagues demonstrated that in healthy patients with relatively short smoking histories and in a healthy nonsmoker control group, coronary blood flow increased by 25% and 40%, respectively, with nicotine use at rest.⁹ However, when these patients were stressed with dipyramidole and while smoking during the examination, myocardial blood flow was reduced by 11% in the study group and 14% in the control group.⁹ This is likely because the patients studied had relatively healthy coronary arteries that were able to maximally dilate when stressed. In this scenario, nicotine’s dilatory effects are offset by nicotine’s α-receptor–mediated vasoconstriction effects.⁹ Of note, patients in the study group experienced a somewhat diminished increase in coronary blood flow at rest with nicotine use, suggesting that even a short smoking history may damage the myocardial endothelium, rendering it less responsive to nicotine’s vasodilatory effects.⁹

Nicotine Replacement Therapy and Stress Testing

Given the association between cigarette smoking and CAD, medical practitioners strongly encourage patients to quit smoking to reduce their risk of adverse cardiovascular outcomes. Various smoking cessation treatments are available for patients. Common, readily accessible forms of therapy include nicotine replacement products (Table 2).

Early studies of NRT in patients with underlying CVD found an increased risk of cardiovascular events, such as myocardial infarction, presumably due to the nicotine content of these products.^13,14 However, the concentration of nicotine in NRT is substantially lower than that found in cigarettes and in some formulations, such as transdermal patches, nicotine is delivered over a prolonged period of time.¹⁵ For this reason, NRT is thought to be safe in patients with underlying CVD and stable ischemic heart disease. A recent systematic review and meta-analysis found that while NRT may be associated with tachycardia, it did not increase the risk of more serious cardiovascular adverse effects (AEs).^16,17

Given the lower nicotine concentration in NRT products, the associated hemodynamic effect of nicotine also is thought to be less pronounced. In a study conducted by Tzivoni and colleagues in patients with CAD using transdermal nicotine patches, no differences in blood pressure, heart rate, ischemia, or arrhythmias were found from baseline to 2 weeks.¹⁸ These findings were further confirmed in a small study by Lucini and colleagues, which found that nicotine patches produced slight hemodynamic effects, but to a lesser extent than cigarette smoking.¹⁹ For the NRT gum formulation, while a small study found that 4 mg produced coronary vasoconstriction in patients with underlying CAD, a study by Nitenberg and Antony demonstrated that healthy and diseased coronary arteries did not significantly constrict while patients were using nicotine gum both before and after a cold pressor test, suggesting a lesser degree of coronary vasoconstriction than nicotine from cigarette smoking.^20,21 Similar findings have been described with the nicotine intranasal spray in a study by Keeley and colleagues, which showed no additional AEs on myocardial demand or vasoconstriction when an intranasal nicotine spray was added to cigarette smoking.²² Importantly, a review of the transdermal and gum formulations found that these less pronounced hemodynamic effects were observed across different doses of NRT; however, further studies are needed to clarify the relationship between NRT dose and cardiovascular effects.²³

Overall, NRT does not seem to activate the SNS to the same degree as nicotine obtained via cigarette smoking and likely does not increase the myocardial oxygen demand as much. Additionally, by containing a lower concentration of nicotine, NRT may not impair the myocardium’s ability to supply oxygen to coronary arteries to the same extent as nicotine from cigarette smoking. Therefore, the effects of NRT on MPI using a stress-inducing medication may not be as pronounced. However, due to study limitations, results should be interpreted cautiously.^18-23

Conclusions

Because of the close relationship between cigarette smoking and CAD, many patients with underlying CVD are either current smokers or may be using NRT for smoking cessation. Therefore, the question of whether to refrain from nicotine use prior to MPI is clinically relevant. Currently, there is a lack of high-quality studies demonstrating the effects of nicotine and NRT on coronary perfusion. Because of this, the impact of nicotine and NRT use on the accuracy of MPI using stress-inducing medications remains uncertain. Nevertheless, given that nicotine and NRT may largely affect the accuracy of imaging results, several institutions have adopted protocols that prohibit patients from using these drugs on the day of nuclear stress testing.

There are currently no data specifying the number of hours to hold nicotine products prior to cardiac stress testing. It is generally recommended that other medications that affect coronary blood flow be held for 5 half-lives before conducting MPI.⁴ Following the same guidance for nicotine and NRT may present a reasonable approach to ensure accurate imaging results. Based on the discussed literature, patients should be instructed to refrain from cigarette smoking for at least 5 to 10 hours prior to MPI, given nicotine’s half-life of about 1 to 2 hours.²⁴

The data for NRT are less clear. While use of NRT may not be an absolute contraindication to conducting MPI, it is important to consider that this may affect the accuracy of results. Given this uncertainty, it is likely ideal to hold NRT prior to MPI, based on the specific formulation of NRT and that product's half-life. Further robust studies are needed to analyze the impact of nicotine and NRT on the accuracy of nuclear stress testing using a medication.

The new 2021 coronary revascularization guidelines are spurring controversy, as surgical associations raise concerns about the interpretation of the evidence behind key recommendations and the makeup of the writing committee.

The guideline was published in December by the American College of Cardiology, American Heart Association, and Society for Cardiovascular Angiography and Interventions (ACC/AHA/SCAI), and replaces the 2011 coronary artery bypass surgery (CABG) and the 2011 and 2015 percutaneous coronary intervention (PCI) guidelines.

The American Association for Thoracic Surgery (AATS) and Society of Thoracic Surgeons (STS) were part of the development of the document but have withdrawn their support, citing three areas of concern in a recent editorial in Annals of Thoracic Surgery.

“I do have to emphasize this is not just the AATS and STS – the European societies, Latin American societies, Asian societies, and even cardiologists are all coming out against these guidelines,” Joseph F. Sabik III, MD, University Hospitals Cleveland Medical Center, lead author of the editorial, said in an interview. “So, I think that tells us that something didn’t go right here.”

The main objection is the downgrading of CABG surgery from a class 1 to weak 2b recommendation to improve survival in patients with three-vessel coronary artery disease (CAD) and normal left ventricular function.

The ISCHEMIA trial was used to support this two-level downgrade and a class 1 to 2a downgrade for CABG in three-vessel CAD with mild to moderate left ventricular dysfunction. But the trial wasn’t powered for survival, only 20% of patients underwent CABG as the initial invasive strategy, and patients were followed for less than 5 years, the editorialists observed.

At the same time, there’s plenty of observational and randomized studies such as SYNTAX, EXCEL, and FAME 3 showing a clear survival benefit of CABG over PCI, Dr. Sabik said. “The criticism is that these are old studies and aren’t applicable today, but we don’t understand downgrading without any evidence suggesting it [CABG] isn’t effective anymore.”
 

CABG and PCI treated as equal

AATS and STS also object to the new guidelines treating PCI and CABG as equivalent revascularization strategies in decreasing ischemic events. Both were given a 2b recommendation for survival with triple-vessel disease, but randomized trials have demonstrated not only lower mortality with surgery but fewer reinterventions and myocardial infarctions.

“None of that gets acknowledged in the guidelines; they are treated equally,” Dr. Sabik said. “So if you’re going to say that CABG isn’t any better than medical therapy, in our mind, you have to say that PCI is worse than medical therapy. And we don’t believe that, I want you to know. We just think that the logic doesn’t make any sense. The committee used what it wanted to but didn’t use many things that committees have used in the past to give CABG a level 1 recommendation.”

The downgrade is also at odds with the 2018 European Society of Cardiology (ESC)/ European Association for Cardio-Thoracic Surgery (EACTS) guidelines, which give CABG a class 1 recommendation in three-vessel CAD as well as one- or two-vessel CAD with proximal left atrial descending artery stenosis.

In a Dec. 14 letter to the ACC/AHA Joint Committee, the Latin American Association of Cardiac and Endovascular Surgery (LACES) also called out the guideline committee for the 2b class of recommendation (COR) for PCI and CABG, saying it contradicts the text, which “clearly considers” the need to give a weaker endorsement for PCI than for CABG in patients with multivessel CAD.

“Considering that this section has the most significant impact due to the prevalence of stable ischemic heart disease in patients with multivessel CAD, such a contradiction may affect the lives and survival of millions of patients worldwide and have a major socioeconomic impact,” the letter states.

“Therefore, LACES respectfully but vehemently believes the Task Force should seriously reconsider the wording and recommendations in this specific large group of patients.”
 

Class I for radial conduit

AATS and STS also express concern about the new class 1 recommendation for the radial artery as a conduit in CABG. They note this is higher than bilateral internal mammary artery grafting and based on a meta-analysis of six relatively small studies with very strict inclusion criteria favorable for radial artery usage and patency.

“There’s a lot of studies that showed if you use the radial artery incorrectly, you have worse outcomes, and that’s what scares us a bit,” Dr. Sabik said. “If they’re giving it a class 1 recommendation, does that mean that becomes standard of care and could that cause patient harm? We think that level 1 is too high and that a [class] 2a with qualifications would be appropriate.”
 

Unequal footing

In a Dec. 23 letter, EACTS said it is “extremely concerned” about downgrading the COR for CABG without new randomized controlled trials to support the decision or to reject previously held evidence.

“The downgrading of CABG, and placing PCI at the same COR, does not meet our interpretation of the evidence, and may lead to avoidable loss of life,” EACTS officials said. “These guidelines also have implications on patient care: A COR IIb entails that CABG may not be reimbursable in some countries.”

EACTS called on AHA, ACC, and SCAI to review the evidence and called out the makeup of the guideline writing committee. “It is astonishing that no surgical association was involved, coauthored, or endorsed these guidelines.”

The AATS and STS each had a single representative on the guidelines’ writing committee but note that the six remaining surgeons were chosen by the ACC and AHA. Surgeons were also in the minority and only a majority was needed to approve the guidelines, highlighting the need to revisit the guideline development process to ensure equal representation by multidisciplinary experts across specialties.

“I hope the cardiology and surgical societies can come together and figure out how we do this better in the future, and we take a look again at these guidelines and come up with what we think is appropriate, especially since this is not just AATS and STS,” Dr. Sabik said.

In an emailed statement, the ACC/AHA said the AATS and STS representatives “actively participated throughout the writing process the past 3 years” and that the AATS and STS were involved in the “extensive peer review process” for the document with a reviewer from each organization. Nevertheless, AATS and STS both elected not to endorse the guidelines when at the organizational approval stage.

“Consequently, the AATS representative chose to stay with the committee and be recognized as having been appointed on behalf of the ACC and the AHA,” according to the statement. “The STS representative chose to withdraw from the committee and is not listed as a writing committee member on the final guideline. The final guideline reflects the latest evidence-based recommendations for coronary artery revascularization, as agreed by the ACC, AHA, SCAI, and the full writing committee.”

Despite pleas from the surgical groups to reconsider the evidence, “there is no further review process for the revascularization guideline,” the ACC/AHA spokesperson noted.

Jennifer S. Lawton, MD, chief of cardiac surgery at Johns Hopkins University, Baltimore, and guideline writing committee chair, did not respond to numerous requests for comment.

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

The new 2021 coronary revascularization guidelines are spurring controversy, as surgical associations raise concerns about the interpretation of the evidence behind key recommendations and the makeup of the writing committee.

The guideline was published in December by the American College of Cardiology, American Heart Association, and Society for Cardiovascular Angiography and Interventions (ACC/AHA/SCAI), and replaces the 2011 coronary artery bypass surgery (CABG) and the 2011 and 2015 percutaneous coronary intervention (PCI) guidelines.

The American Association for Thoracic Surgery (AATS) and Society of Thoracic Surgeons (STS) were part of the development of the document but have withdrawn their support, citing three areas of concern in a recent editorial in Annals of Thoracic Surgery.

“I do have to emphasize this is not just the AATS and STS – the European societies, Latin American societies, Asian societies, and even cardiologists are all coming out against these guidelines,” Joseph F. Sabik III, MD, University Hospitals Cleveland Medical Center, lead author of the editorial, said in an interview. “So, I think that tells us that something didn’t go right here.”

The main objection is the downgrading of CABG surgery from a class 1 to weak 2b recommendation to improve survival in patients with three-vessel coronary artery disease (CAD) and normal left ventricular function.

The ISCHEMIA trial was used to support this two-level downgrade and a class 1 to 2a downgrade for CABG in three-vessel CAD with mild to moderate left ventricular dysfunction. But the trial wasn’t powered for survival, only 20% of patients underwent CABG as the initial invasive strategy, and patients were followed for less than 5 years, the editorialists observed.

At the same time, there’s plenty of observational and randomized studies such as SYNTAX, EXCEL, and FAME 3 showing a clear survival benefit of CABG over PCI, Dr. Sabik said. “The criticism is that these are old studies and aren’t applicable today, but we don’t understand downgrading without any evidence suggesting it [CABG] isn’t effective anymore.”
 

CABG and PCI treated as equal

AATS and STS also object to the new guidelines treating PCI and CABG as equivalent revascularization strategies in decreasing ischemic events. Both were given a 2b recommendation for survival with triple-vessel disease, but randomized trials have demonstrated not only lower mortality with surgery but fewer reinterventions and myocardial infarctions.

“None of that gets acknowledged in the guidelines; they are treated equally,” Dr. Sabik said. “So if you’re going to say that CABG isn’t any better than medical therapy, in our mind, you have to say that PCI is worse than medical therapy. And we don’t believe that, I want you to know. We just think that the logic doesn’t make any sense. The committee used what it wanted to but didn’t use many things that committees have used in the past to give CABG a level 1 recommendation.”

The downgrade is also at odds with the 2018 European Society of Cardiology (ESC)/ European Association for Cardio-Thoracic Surgery (EACTS) guidelines, which give CABG a class 1 recommendation in three-vessel CAD as well as one- or two-vessel CAD with proximal left atrial descending artery stenosis.

In a Dec. 14 letter to the ACC/AHA Joint Committee, the Latin American Association of Cardiac and Endovascular Surgery (LACES) also called out the guideline committee for the 2b class of recommendation (COR) for PCI and CABG, saying it contradicts the text, which “clearly considers” the need to give a weaker endorsement for PCI than for CABG in patients with multivessel CAD.

“Considering that this section has the most significant impact due to the prevalence of stable ischemic heart disease in patients with multivessel CAD, such a contradiction may affect the lives and survival of millions of patients worldwide and have a major socioeconomic impact,” the letter states.

“Therefore, LACES respectfully but vehemently believes the Task Force should seriously reconsider the wording and recommendations in this specific large group of patients.”
 

Class I for radial conduit

AATS and STS also express concern about the new class 1 recommendation for the radial artery as a conduit in CABG. They note this is higher than bilateral internal mammary artery grafting and based on a meta-analysis of six relatively small studies with very strict inclusion criteria favorable for radial artery usage and patency.

“There’s a lot of studies that showed if you use the radial artery incorrectly, you have worse outcomes, and that’s what scares us a bit,” Dr. Sabik said. “If they’re giving it a class 1 recommendation, does that mean that becomes standard of care and could that cause patient harm? We think that level 1 is too high and that a [class] 2a with qualifications would be appropriate.”
 

Unequal footing

In a Dec. 23 letter, EACTS said it is “extremely concerned” about downgrading the COR for CABG without new randomized controlled trials to support the decision or to reject previously held evidence.

“The downgrading of CABG, and placing PCI at the same COR, does not meet our interpretation of the evidence, and may lead to avoidable loss of life,” EACTS officials said. “These guidelines also have implications on patient care: A COR IIb entails that CABG may not be reimbursable in some countries.”

EACTS called on AHA, ACC, and SCAI to review the evidence and called out the makeup of the guideline writing committee. “It is astonishing that no surgical association was involved, coauthored, or endorsed these guidelines.”

The AATS and STS each had a single representative on the guidelines’ writing committee but note that the six remaining surgeons were chosen by the ACC and AHA. Surgeons were also in the minority and only a majority was needed to approve the guidelines, highlighting the need to revisit the guideline development process to ensure equal representation by multidisciplinary experts across specialties.

“I hope the cardiology and surgical societies can come together and figure out how we do this better in the future, and we take a look again at these guidelines and come up with what we think is appropriate, especially since this is not just AATS and STS,” Dr. Sabik said.

In an emailed statement, the ACC/AHA said the AATS and STS representatives “actively participated throughout the writing process the past 3 years” and that the AATS and STS were involved in the “extensive peer review process” for the document with a reviewer from each organization. Nevertheless, AATS and STS both elected not to endorse the guidelines when at the organizational approval stage.

“Consequently, the AATS representative chose to stay with the committee and be recognized as having been appointed on behalf of the ACC and the AHA,” according to the statement. “The STS representative chose to withdraw from the committee and is not listed as a writing committee member on the final guideline. The final guideline reflects the latest evidence-based recommendations for coronary artery revascularization, as agreed by the ACC, AHA, SCAI, and the full writing committee.”

Despite pleas from the surgical groups to reconsider the evidence, “there is no further review process for the revascularization guideline,” the ACC/AHA spokesperson noted.

Jennifer S. Lawton, MD, chief of cardiac surgery at Johns Hopkins University, Baltimore, and guideline writing committee chair, did not respond to numerous requests for comment.

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

The new 2021 coronary revascularization guidelines are spurring controversy, as surgical associations raise concerns about the interpretation of the evidence behind key recommendations and the makeup of the writing committee.

The guideline was published in December by the American College of Cardiology, American Heart Association, and Society for Cardiovascular Angiography and Interventions (ACC/AHA/SCAI), and replaces the 2011 coronary artery bypass surgery (CABG) and the 2011 and 2015 percutaneous coronary intervention (PCI) guidelines.

The American Association for Thoracic Surgery (AATS) and Society of Thoracic Surgeons (STS) were part of the development of the document but have withdrawn their support, citing three areas of concern in a recent editorial in Annals of Thoracic Surgery.

“I do have to emphasize this is not just the AATS and STS – the European societies, Latin American societies, Asian societies, and even cardiologists are all coming out against these guidelines,” Joseph F. Sabik III, MD, University Hospitals Cleveland Medical Center, lead author of the editorial, said in an interview. “So, I think that tells us that something didn’t go right here.”

The main objection is the downgrading of CABG surgery from a class 1 to weak 2b recommendation to improve survival in patients with three-vessel coronary artery disease (CAD) and normal left ventricular function.

The ISCHEMIA trial was used to support this two-level downgrade and a class 1 to 2a downgrade for CABG in three-vessel CAD with mild to moderate left ventricular dysfunction. But the trial wasn’t powered for survival, only 20% of patients underwent CABG as the initial invasive strategy, and patients were followed for less than 5 years, the editorialists observed.

At the same time, there’s plenty of observational and randomized studies such as SYNTAX, EXCEL, and FAME 3 showing a clear survival benefit of CABG over PCI, Dr. Sabik said. “The criticism is that these are old studies and aren’t applicable today, but we don’t understand downgrading without any evidence suggesting it [CABG] isn’t effective anymore.”
 

CABG and PCI treated as equal

AATS and STS also object to the new guidelines treating PCI and CABG as equivalent revascularization strategies in decreasing ischemic events. Both were given a 2b recommendation for survival with triple-vessel disease, but randomized trials have demonstrated not only lower mortality with surgery but fewer reinterventions and myocardial infarctions.

“None of that gets acknowledged in the guidelines; they are treated equally,” Dr. Sabik said. “So if you’re going to say that CABG isn’t any better than medical therapy, in our mind, you have to say that PCI is worse than medical therapy. And we don’t believe that, I want you to know. We just think that the logic doesn’t make any sense. The committee used what it wanted to but didn’t use many things that committees have used in the past to give CABG a level 1 recommendation.”

The downgrade is also at odds with the 2018 European Society of Cardiology (ESC)/ European Association for Cardio-Thoracic Surgery (EACTS) guidelines, which give CABG a class 1 recommendation in three-vessel CAD as well as one- or two-vessel CAD with proximal left atrial descending artery stenosis.

In a Dec. 14 letter to the ACC/AHA Joint Committee, the Latin American Association of Cardiac and Endovascular Surgery (LACES) also called out the guideline committee for the 2b class of recommendation (COR) for PCI and CABG, saying it contradicts the text, which “clearly considers” the need to give a weaker endorsement for PCI than for CABG in patients with multivessel CAD.

“Considering that this section has the most significant impact due to the prevalence of stable ischemic heart disease in patients with multivessel CAD, such a contradiction may affect the lives and survival of millions of patients worldwide and have a major socioeconomic impact,” the letter states.

“Therefore, LACES respectfully but vehemently believes the Task Force should seriously reconsider the wording and recommendations in this specific large group of patients.”
 

Class I for radial conduit

AATS and STS also express concern about the new class 1 recommendation for the radial artery as a conduit in CABG. They note this is higher than bilateral internal mammary artery grafting and based on a meta-analysis of six relatively small studies with very strict inclusion criteria favorable for radial artery usage and patency.

“There’s a lot of studies that showed if you use the radial artery incorrectly, you have worse outcomes, and that’s what scares us a bit,” Dr. Sabik said. “If they’re giving it a class 1 recommendation, does that mean that becomes standard of care and could that cause patient harm? We think that level 1 is too high and that a [class] 2a with qualifications would be appropriate.”
 

Unequal footing

In a Dec. 23 letter, EACTS said it is “extremely concerned” about downgrading the COR for CABG without new randomized controlled trials to support the decision or to reject previously held evidence.

“The downgrading of CABG, and placing PCI at the same COR, does not meet our interpretation of the evidence, and may lead to avoidable loss of life,” EACTS officials said. “These guidelines also have implications on patient care: A COR IIb entails that CABG may not be reimbursable in some countries.”

EACTS called on AHA, ACC, and SCAI to review the evidence and called out the makeup of the guideline writing committee. “It is astonishing that no surgical association was involved, coauthored, or endorsed these guidelines.”

The AATS and STS each had a single representative on the guidelines’ writing committee but note that the six remaining surgeons were chosen by the ACC and AHA. Surgeons were also in the minority and only a majority was needed to approve the guidelines, highlighting the need to revisit the guideline development process to ensure equal representation by multidisciplinary experts across specialties.

“I hope the cardiology and surgical societies can come together and figure out how we do this better in the future, and we take a look again at these guidelines and come up with what we think is appropriate, especially since this is not just AATS and STS,” Dr. Sabik said.

In an emailed statement, the ACC/AHA said the AATS and STS representatives “actively participated throughout the writing process the past 3 years” and that the AATS and STS were involved in the “extensive peer review process” for the document with a reviewer from each organization. Nevertheless, AATS and STS both elected not to endorse the guidelines when at the organizational approval stage.

“Consequently, the AATS representative chose to stay with the committee and be recognized as having been appointed on behalf of the ACC and the AHA,” according to the statement. “The STS representative chose to withdraw from the committee and is not listed as a writing committee member on the final guideline. The final guideline reflects the latest evidence-based recommendations for coronary artery revascularization, as agreed by the ACC, AHA, SCAI, and the full writing committee.”

Despite pleas from the surgical groups to reconsider the evidence, “there is no further review process for the revascularization guideline,” the ACC/AHA spokesperson noted.

Jennifer S. Lawton, MD, chief of cardiac surgery at Johns Hopkins University, Baltimore, and guideline writing committee chair, did not respond to numerous requests for comment.

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

Even though men in midlife have more cardiovascular (CV) conditions and risk factors than women of the same age, women are more affected by these conditions in terms of cognitive decline, new research suggests.

Analyses of almost 1,400 participants in the population-based Mayo Clinic Study of Aging showed that diabetes, dyslipidemia, and coronary heart disease (CHD) all had stronger associations with global cognitive decline in women than in men.

“All men and women should be treated for cardiovascular risk factors and conditions, but this study really highlights the importance of very early and perhaps more aggressive treatment in women with these conditions,” co-investigator Michelle M. Mielke, PhD, professor of epidemiology and neurology, Mayo Clinic, Rochester, Minn., told this news organization.

The findings were published online Jan. 5 in Neurology.
 

Assessing sex differences

Most previous studies in this area have focused on CV risk factors in midlife in relation to late-life dementia (after age 75) or on late-life vascular risk factors and late-life dementia, Dr. Mielke noted.

However, a few recent studies have suggested vascular risk factors can affect cognition even in midlife. The current investigators sought to determine whether there are sex differences in these associations.

They assessed 1,857 nondemented participants aged 50 to 69 years from the Mayo Clinic Study on Aging. The mean education level was 14.9 years, and the mean body mass index (BMI) was 29.7.

Among the participants, 78.9% had at least one CV condition or risk factor, and the proportion was higher in men than women (83.4% vs. 74.5%; P < .0001).

Frequency of each individual CV condition or risk factor was also higher in men than women, and they had more years of education and higher BMI but took fewer medications.

Every 15 months, participants had an in-person interview and physical examination that included a neurologic assessment and short test of memory.

The neuropsychological battery included nine tests across four domains: memory, language, executive function, and visuospatial skills. Researchers calculated z-scores for these domains and for global cognition.
 

Multiple cognitive domains

Whereas this study evaluated multiple cognitive domains, most previous research has focused on global cognitive decline and/or decline in only one or two cognitive domains, the investigators note.

They collected information from medical records on CV conditions such as CHD, arrhythmias, congestive heart failure, peripheral vascular disease (PVD), and stroke; and CV risk factors such as hypertension, diabetes, dyslipidemia, smoking status, and BMI.

Because of the small number of patients with stroke and PVD, these were classified as “other cardiovascular conditions” in the statistical analysis.

Researchers adjusted for sex, age, years of education, depressive symptoms, comorbidities, medications, and apolipoprotein E (APOE) genotyping. The mean follow-up was 3 years and did not differ by sex.

As some participants didn’t have a follow-up visit, the current analysis included 1,394 individuals. Those without follow-up visits were younger, had less education and more comorbidities, and took more medications compared with those with a follow-up.

Results showed most CV conditions were more strongly associated with cognitive function among women than men. For example, CHD was associated with global decline only in women (P < .05).

CHD, diabetes, and dyslipidemia were associated with language decline in women only (all, P < .05), but congestive heart failure was significantly associated with language decline in men only.

Dr. Mielke cautioned about reading too much into the language results for women.

“It’s an intriguing finding and definitely we need to follow up on it,” she said. However, “more studies are needed to examine sex differences before we start saying it only has an effect on language.”
 

‘Treat aggressively and right away’

The researchers were somewhat surprised by the study findings. Because there is a higher prevalence of CV conditions and risk factors in men, they presumed men would be more affected by these conditions, said Dr. Mielke.

“But that’s not what we saw; we saw the reverse. It was actually the women who were affected more by these cardiovascular risk factors and conditions,” she said.

As midlife is when women enter menopause, fluctuating estrogen levels may help explain the differential impact on cognition among women. But Dr. Mielke said she wants to “move beyond” just looking at hormones.

She pointed out there are a variety of psychosocial factors that may also contribute to an imbalance in the cognitive impact of CV conditions on women.

“Midlife is when many women are still taking care of their children at home, are also taking care of their adult parents, and may be undergoing more stress while continuing to do a job,” Dr. Miekle said.

Structural brain development and genetics may also contribute to the greater effect on cognition in women, the investigators note.

Dr. Mielke stressed that the current study only identifies associations. “The next steps are to understand what some of the underlying mechanisms for this are,” she said.

In the meantime, these new results suggest middle-aged women with high blood pressure, cholesterol, or glucose measures “should be treated aggressively and right away” said Dr. Mielke.

“For example, for women who are just starting to become hypertensive, clinicians should treat them right away and not watch and wait.”

Study limitations cited include that its sample was limited to Olmsted County, Minnesota – so results may not be generalized to other populations. Also, as researchers combined PVD and stroke into one group, larger sample sizes are needed, especially for stroke. Another limitation was the study did not have information on duration of all CV conditions or risk factors.
 

Helpful for tailoring interventions?

Commenting on the study, Glen R. Finney, MD, director, Memory and Cognition Program, Geisinger Health Clinic, Wilkes-Barre, Pennsylvania, said the results are important.

“The more we understand about risk factors for the development of Alzheimer’s disease and related dementias, the better we understand how we can reduce the risks,” said Dr. Finney, who was not involved with the research.

Awareness that CV conditions are major risk factors in midlife has been “definitely rising,” said Dr. Finney. “Many studies originally were looking at late life and are now looking more at earlier in the disease process, and I think that’s important.”

Understanding how sex, ethnicity, and other demographic variables affect risks can help to “tailor interventions” for individual patients, he said.

The study was supported by the National Institutes of Health, the GHR Foundation, and the Rochester Epidemiology Project. Dr. Mielke is a consultant for Biogen and Brain Protection Company and is on the editorial boards of Neurology and Alzheimer’s and Dementia. Dr. Finney has reported no relevant financial relationships.

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

Even though men in midlife have more cardiovascular (CV) conditions and risk factors than women of the same age, women are more affected by these conditions in terms of cognitive decline, new research suggests.

Analyses of almost 1,400 participants in the population-based Mayo Clinic Study of Aging showed that diabetes, dyslipidemia, and coronary heart disease (CHD) all had stronger associations with global cognitive decline in women than in men.

“All men and women should be treated for cardiovascular risk factors and conditions, but this study really highlights the importance of very early and perhaps more aggressive treatment in women with these conditions,” co-investigator Michelle M. Mielke, PhD, professor of epidemiology and neurology, Mayo Clinic, Rochester, Minn., told this news organization.

The findings were published online Jan. 5 in Neurology.
 

Assessing sex differences

Most previous studies in this area have focused on CV risk factors in midlife in relation to late-life dementia (after age 75) or on late-life vascular risk factors and late-life dementia, Dr. Mielke noted.

However, a few recent studies have suggested vascular risk factors can affect cognition even in midlife. The current investigators sought to determine whether there are sex differences in these associations.

They assessed 1,857 nondemented participants aged 50 to 69 years from the Mayo Clinic Study on Aging. The mean education level was 14.9 years, and the mean body mass index (BMI) was 29.7.

Among the participants, 78.9% had at least one CV condition or risk factor, and the proportion was higher in men than women (83.4% vs. 74.5%; P < .0001).

Frequency of each individual CV condition or risk factor was also higher in men than women, and they had more years of education and higher BMI but took fewer medications.

Every 15 months, participants had an in-person interview and physical examination that included a neurologic assessment and short test of memory.

The neuropsychological battery included nine tests across four domains: memory, language, executive function, and visuospatial skills. Researchers calculated z-scores for these domains and for global cognition.
 

Multiple cognitive domains

Whereas this study evaluated multiple cognitive domains, most previous research has focused on global cognitive decline and/or decline in only one or two cognitive domains, the investigators note.

They collected information from medical records on CV conditions such as CHD, arrhythmias, congestive heart failure, peripheral vascular disease (PVD), and stroke; and CV risk factors such as hypertension, diabetes, dyslipidemia, smoking status, and BMI.

Because of the small number of patients with stroke and PVD, these were classified as “other cardiovascular conditions” in the statistical analysis.

Researchers adjusted for sex, age, years of education, depressive symptoms, comorbidities, medications, and apolipoprotein E (APOE) genotyping. The mean follow-up was 3 years and did not differ by sex.

As some participants didn’t have a follow-up visit, the current analysis included 1,394 individuals. Those without follow-up visits were younger, had less education and more comorbidities, and took more medications compared with those with a follow-up.

Results showed most CV conditions were more strongly associated with cognitive function among women than men. For example, CHD was associated with global decline only in women (P < .05).

CHD, diabetes, and dyslipidemia were associated with language decline in women only (all, P < .05), but congestive heart failure was significantly associated with language decline in men only.

Dr. Mielke cautioned about reading too much into the language results for women.

“It’s an intriguing finding and definitely we need to follow up on it,” she said. However, “more studies are needed to examine sex differences before we start saying it only has an effect on language.”
 

‘Treat aggressively and right away’

The researchers were somewhat surprised by the study findings. Because there is a higher prevalence of CV conditions and risk factors in men, they presumed men would be more affected by these conditions, said Dr. Mielke.

“But that’s not what we saw; we saw the reverse. It was actually the women who were affected more by these cardiovascular risk factors and conditions,” she said.

As midlife is when women enter menopause, fluctuating estrogen levels may help explain the differential impact on cognition among women. But Dr. Mielke said she wants to “move beyond” just looking at hormones.

She pointed out there are a variety of psychosocial factors that may also contribute to an imbalance in the cognitive impact of CV conditions on women.

“Midlife is when many women are still taking care of their children at home, are also taking care of their adult parents, and may be undergoing more stress while continuing to do a job,” Dr. Miekle said.

Structural brain development and genetics may also contribute to the greater effect on cognition in women, the investigators note.

Dr. Mielke stressed that the current study only identifies associations. “The next steps are to understand what some of the underlying mechanisms for this are,” she said.

In the meantime, these new results suggest middle-aged women with high blood pressure, cholesterol, or glucose measures “should be treated aggressively and right away” said Dr. Mielke.

“For example, for women who are just starting to become hypertensive, clinicians should treat them right away and not watch and wait.”

Study limitations cited include that its sample was limited to Olmsted County, Minnesota – so results may not be generalized to other populations. Also, as researchers combined PVD and stroke into one group, larger sample sizes are needed, especially for stroke. Another limitation was the study did not have information on duration of all CV conditions or risk factors.
 

Helpful for tailoring interventions?

Commenting on the study, Glen R. Finney, MD, director, Memory and Cognition Program, Geisinger Health Clinic, Wilkes-Barre, Pennsylvania, said the results are important.

“The more we understand about risk factors for the development of Alzheimer’s disease and related dementias, the better we understand how we can reduce the risks,” said Dr. Finney, who was not involved with the research.

Awareness that CV conditions are major risk factors in midlife has been “definitely rising,” said Dr. Finney. “Many studies originally were looking at late life and are now looking more at earlier in the disease process, and I think that’s important.”

Understanding how sex, ethnicity, and other demographic variables affect risks can help to “tailor interventions” for individual patients, he said.

The study was supported by the National Institutes of Health, the GHR Foundation, and the Rochester Epidemiology Project. Dr. Mielke is a consultant for Biogen and Brain Protection Company and is on the editorial boards of Neurology and Alzheimer’s and Dementia. Dr. Finney has reported no relevant financial relationships.

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

Even though men in midlife have more cardiovascular (CV) conditions and risk factors than women of the same age, women are more affected by these conditions in terms of cognitive decline, new research suggests.

Analyses of almost 1,400 participants in the population-based Mayo Clinic Study of Aging showed that diabetes, dyslipidemia, and coronary heart disease (CHD) all had stronger associations with global cognitive decline in women than in men.

“All men and women should be treated for cardiovascular risk factors and conditions, but this study really highlights the importance of very early and perhaps more aggressive treatment in women with these conditions,” co-investigator Michelle M. Mielke, PhD, professor of epidemiology and neurology, Mayo Clinic, Rochester, Minn., told this news organization.

The findings were published online Jan. 5 in Neurology.
 

Assessing sex differences

Most previous studies in this area have focused on CV risk factors in midlife in relation to late-life dementia (after age 75) or on late-life vascular risk factors and late-life dementia, Dr. Mielke noted.

However, a few recent studies have suggested vascular risk factors can affect cognition even in midlife. The current investigators sought to determine whether there are sex differences in these associations.

They assessed 1,857 nondemented participants aged 50 to 69 years from the Mayo Clinic Study on Aging. The mean education level was 14.9 years, and the mean body mass index (BMI) was 29.7.

Among the participants, 78.9% had at least one CV condition or risk factor, and the proportion was higher in men than women (83.4% vs. 74.5%; P < .0001).

Frequency of each individual CV condition or risk factor was also higher in men than women, and they had more years of education and higher BMI but took fewer medications.

Every 15 months, participants had an in-person interview and physical examination that included a neurologic assessment and short test of memory.

The neuropsychological battery included nine tests across four domains: memory, language, executive function, and visuospatial skills. Researchers calculated z-scores for these domains and for global cognition.
 

Multiple cognitive domains

Whereas this study evaluated multiple cognitive domains, most previous research has focused on global cognitive decline and/or decline in only one or two cognitive domains, the investigators note.

They collected information from medical records on CV conditions such as CHD, arrhythmias, congestive heart failure, peripheral vascular disease (PVD), and stroke; and CV risk factors such as hypertension, diabetes, dyslipidemia, smoking status, and BMI.

Because of the small number of patients with stroke and PVD, these were classified as “other cardiovascular conditions” in the statistical analysis.

Researchers adjusted for sex, age, years of education, depressive symptoms, comorbidities, medications, and apolipoprotein E (APOE) genotyping. The mean follow-up was 3 years and did not differ by sex.

As some participants didn’t have a follow-up visit, the current analysis included 1,394 individuals. Those without follow-up visits were younger, had less education and more comorbidities, and took more medications compared with those with a follow-up.

Results showed most CV conditions were more strongly associated with cognitive function among women than men. For example, CHD was associated with global decline only in women (P < .05).

CHD, diabetes, and dyslipidemia were associated with language decline in women only (all, P < .05), but congestive heart failure was significantly associated with language decline in men only.

Dr. Mielke cautioned about reading too much into the language results for women.

“It’s an intriguing finding and definitely we need to follow up on it,” she said. However, “more studies are needed to examine sex differences before we start saying it only has an effect on language.”
 

‘Treat aggressively and right away’

The researchers were somewhat surprised by the study findings. Because there is a higher prevalence of CV conditions and risk factors in men, they presumed men would be more affected by these conditions, said Dr. Mielke.

“But that’s not what we saw; we saw the reverse. It was actually the women who were affected more by these cardiovascular risk factors and conditions,” she said.

As midlife is when women enter menopause, fluctuating estrogen levels may help explain the differential impact on cognition among women. But Dr. Mielke said she wants to “move beyond” just looking at hormones.

She pointed out there are a variety of psychosocial factors that may also contribute to an imbalance in the cognitive impact of CV conditions on women.

“Midlife is when many women are still taking care of their children at home, are also taking care of their adult parents, and may be undergoing more stress while continuing to do a job,” Dr. Miekle said.

Structural brain development and genetics may also contribute to the greater effect on cognition in women, the investigators note.

Dr. Mielke stressed that the current study only identifies associations. “The next steps are to understand what some of the underlying mechanisms for this are,” she said.

In the meantime, these new results suggest middle-aged women with high blood pressure, cholesterol, or glucose measures “should be treated aggressively and right away” said Dr. Mielke.

“For example, for women who are just starting to become hypertensive, clinicians should treat them right away and not watch and wait.”

Study limitations cited include that its sample was limited to Olmsted County, Minnesota – so results may not be generalized to other populations. Also, as researchers combined PVD and stroke into one group, larger sample sizes are needed, especially for stroke. Another limitation was the study did not have information on duration of all CV conditions or risk factors.
 

Helpful for tailoring interventions?

Commenting on the study, Glen R. Finney, MD, director, Memory and Cognition Program, Geisinger Health Clinic, Wilkes-Barre, Pennsylvania, said the results are important.

“The more we understand about risk factors for the development of Alzheimer’s disease and related dementias, the better we understand how we can reduce the risks,” said Dr. Finney, who was not involved with the research.

Awareness that CV conditions are major risk factors in midlife has been “definitely rising,” said Dr. Finney. “Many studies originally were looking at late life and are now looking more at earlier in the disease process, and I think that’s important.”

Understanding how sex, ethnicity, and other demographic variables affect risks can help to “tailor interventions” for individual patients, he said.

The study was supported by the National Institutes of Health, the GHR Foundation, and the Rochester Epidemiology Project. Dr. Mielke is a consultant for Biogen and Brain Protection Company and is on the editorial boards of Neurology and Alzheimer’s and Dementia. Dr. Finney has reported no relevant financial relationships.

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

Sodium-glucose cotransporter 2 (SGLT2) inhibitors show “remarkable consistency of class benefit” for improving cardiovascular outcomes in high-risk people across age, sex, and race/ethnicity categories.

The findings, from a meta-analysis of 10 major randomized clinical trials, were published online Jan. 5, 2021, in JAMA Network Open by Mukul Bhattarai, MD, a cardiology fellow at Southern Illinois University, Springfield, and colleagues.

“Our meta-analysis evaluated a wide spectrum of efficacy outcomes, further characterizing the primary outcome in different subgroups from several well-designed large clinical trials. It supports that SGLT2 inhibitors have emerged as an effective class of drugs for improving cardiovascular morbidity and mortality, including the prevention of [hospitalization for heart failure] and reducing all-cause mortality in selected patients,” Dr. Bhattarai and colleagues wrote.

The cardiovascular outcomes of SGLT2 inhibitor therapy, they noted, “can be compared across all trials, and it demonstrates remarkable consistency of class benefit, despite the variations in populations enrolled.”

However, they also noted that SGLT inhibitors did not reduce the risk of acute MIn overall, and that most of the trials were short term, with a mean follow-up of just 2.3 years.
 

Ten trials, consistent cardiovascular benefits

Dr. Bhattarai and colleagues searched the literature through Jan. 10, 2021, as well as meeting presentations and other sources. They identified 10 placebo-controlled, randomized clinical trials in which participants had atherosclerotic cardiovascular disease or ASCVD risk factors, diabetes, or heart failure. Among a total of 71,553 high-risk patients, 39,053 received an SGLT2 inhibitor and 32,500 received a placebo.

The primary outcome of cardiovascular death or hospitalization for heart failure occurred in 8.10% randomized to SGLT2 inhibitors, compared with 11.56% in the placebo group, a significant difference with odds ratio 0.67 (P < .001). Both individual outcomes were lower in the SGLT2-inhibitor group, with a number needed to treat of 5.7 (P < .001).

Patients receiving SGLT2 inhibitors also had significantly lower rates of major adverse cardiovascular events, defined as death due to cardiovascular causes, nonfatal MI, or nonfatal stroke. Those events occurred in 9.82% versus 10.22%(OR, 0.90; P = .03).

Hospitalizations and ED visits with heart failure were also reduced with SGLT2 inhibitors (4.37% vs. 6.81%; OR, 0.67; P < .001), as was cardiovascular death (4.65% vs. 5.14%; OR, 0.87; P = .009). The reduction in heart failure is likely caused by a combination of a natriuretic effect and reduced interstitial fluid, along with inhibition of cardiac fibrosis, the authors said.

On the other hand, no reductions were seen in acute MI, evaluated in five of the studies. That event occurred in 4.66% taking SGLT2 inhibitors, compared with 4.70% of the placebo group, a nonsignificant difference with an OR of 0.95 (P = 0.22). This is likely because of the fact that SGLT2 inhibitors don’t have known antianginal properties or vasodilatory effects, they don’t reduce myocardial oxygen consumption, and they don’t prevent cardiac muscle remodeling, they noted.

All-cause mortality was significantly lower with SGLT2 inhibitors, though, at 7.09% versus 7.86% (odds ratio, 0.87; P = .004).
 

Benefits seen across age, sex, and race/ethnicity subgroups

While no differences in benefit were found between men and women when compared with placebo groups, the rates of cardiovascular death or heart failure hospitalizations were slightly higher in men than in women (9.01% [OR, 0.75; P < .001] vs. 5.34% [OR, 0.78; P = .002]).

By age, SGLT2 inhibitors benefited people both those younger than 65 years and those aged 65 years and older, although the primary outcome was slightly lower in the younger group (6.94% [OR, 0.79; P < 0.001] vs. 10.47% [OR, 0.78; P < .001]).

And by race, similar benefits from SGLT2 inhibitors were seen among individuals who were White, compared with those who were Asian, Black, or of other race/ethnicity, with event rates of 8.77% (OR, 0.82; P < .001) and 8.75% (OR, 0.66; P = .06), respectively.

“Owing to the short-term trial durations, future long-term prospective studies and postmarketing surveillance studies are warranted to discover the rate of cardiovascular outcomes,” Dr. Bhattarai and colleagues concluded.

The authors have no disclosures.

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

Sodium-glucose cotransporter 2 (SGLT2) inhibitors show “remarkable consistency of class benefit” for improving cardiovascular outcomes in high-risk people across age, sex, and race/ethnicity categories.

The findings, from a meta-analysis of 10 major randomized clinical trials, were published online Jan. 5, 2021, in JAMA Network Open by Mukul Bhattarai, MD, a cardiology fellow at Southern Illinois University, Springfield, and colleagues.

“Our meta-analysis evaluated a wide spectrum of efficacy outcomes, further characterizing the primary outcome in different subgroups from several well-designed large clinical trials. It supports that SGLT2 inhibitors have emerged as an effective class of drugs for improving cardiovascular morbidity and mortality, including the prevention of [hospitalization for heart failure] and reducing all-cause mortality in selected patients,” Dr. Bhattarai and colleagues wrote.

The cardiovascular outcomes of SGLT2 inhibitor therapy, they noted, “can be compared across all trials, and it demonstrates remarkable consistency of class benefit, despite the variations in populations enrolled.”

However, they also noted that SGLT inhibitors did not reduce the risk of acute MIn overall, and that most of the trials were short term, with a mean follow-up of just 2.3 years.
 

Ten trials, consistent cardiovascular benefits

Dr. Bhattarai and colleagues searched the literature through Jan. 10, 2021, as well as meeting presentations and other sources. They identified 10 placebo-controlled, randomized clinical trials in which participants had atherosclerotic cardiovascular disease or ASCVD risk factors, diabetes, or heart failure. Among a total of 71,553 high-risk patients, 39,053 received an SGLT2 inhibitor and 32,500 received a placebo.

The primary outcome of cardiovascular death or hospitalization for heart failure occurred in 8.10% randomized to SGLT2 inhibitors, compared with 11.56% in the placebo group, a significant difference with odds ratio 0.67 (P < .001). Both individual outcomes were lower in the SGLT2-inhibitor group, with a number needed to treat of 5.7 (P < .001).

Patients receiving SGLT2 inhibitors also had significantly lower rates of major adverse cardiovascular events, defined as death due to cardiovascular causes, nonfatal MI, or nonfatal stroke. Those events occurred in 9.82% versus 10.22%(OR, 0.90; P = .03).

Hospitalizations and ED visits with heart failure were also reduced with SGLT2 inhibitors (4.37% vs. 6.81%; OR, 0.67; P < .001), as was cardiovascular death (4.65% vs. 5.14%; OR, 0.87; P = .009). The reduction in heart failure is likely caused by a combination of a natriuretic effect and reduced interstitial fluid, along with inhibition of cardiac fibrosis, the authors said.

On the other hand, no reductions were seen in acute MI, evaluated in five of the studies. That event occurred in 4.66% taking SGLT2 inhibitors, compared with 4.70% of the placebo group, a nonsignificant difference with an OR of 0.95 (P = 0.22). This is likely because of the fact that SGLT2 inhibitors don’t have known antianginal properties or vasodilatory effects, they don’t reduce myocardial oxygen consumption, and they don’t prevent cardiac muscle remodeling, they noted.

All-cause mortality was significantly lower with SGLT2 inhibitors, though, at 7.09% versus 7.86% (odds ratio, 0.87; P = .004).
 

Benefits seen across age, sex, and race/ethnicity subgroups

While no differences in benefit were found between men and women when compared with placebo groups, the rates of cardiovascular death or heart failure hospitalizations were slightly higher in men than in women (9.01% [OR, 0.75; P < .001] vs. 5.34% [OR, 0.78; P = .002]).

By age, SGLT2 inhibitors benefited people both those younger than 65 years and those aged 65 years and older, although the primary outcome was slightly lower in the younger group (6.94% [OR, 0.79; P < 0.001] vs. 10.47% [OR, 0.78; P < .001]).

And by race, similar benefits from SGLT2 inhibitors were seen among individuals who were White, compared with those who were Asian, Black, or of other race/ethnicity, with event rates of 8.77% (OR, 0.82; P < .001) and 8.75% (OR, 0.66; P = .06), respectively.

“Owing to the short-term trial durations, future long-term prospective studies and postmarketing surveillance studies are warranted to discover the rate of cardiovascular outcomes,” Dr. Bhattarai and colleagues concluded.

The authors have no disclosures.

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

Sodium-glucose cotransporter 2 (SGLT2) inhibitors show “remarkable consistency of class benefit” for improving cardiovascular outcomes in high-risk people across age, sex, and race/ethnicity categories.

The findings, from a meta-analysis of 10 major randomized clinical trials, were published online Jan. 5, 2021, in JAMA Network Open by Mukul Bhattarai, MD, a cardiology fellow at Southern Illinois University, Springfield, and colleagues.

“Our meta-analysis evaluated a wide spectrum of efficacy outcomes, further characterizing the primary outcome in different subgroups from several well-designed large clinical trials. It supports that SGLT2 inhibitors have emerged as an effective class of drugs for improving cardiovascular morbidity and mortality, including the prevention of [hospitalization for heart failure] and reducing all-cause mortality in selected patients,” Dr. Bhattarai and colleagues wrote.

The cardiovascular outcomes of SGLT2 inhibitor therapy, they noted, “can be compared across all trials, and it demonstrates remarkable consistency of class benefit, despite the variations in populations enrolled.”

However, they also noted that SGLT inhibitors did not reduce the risk of acute MIn overall, and that most of the trials were short term, with a mean follow-up of just 2.3 years.
 

Ten trials, consistent cardiovascular benefits

Dr. Bhattarai and colleagues searched the literature through Jan. 10, 2021, as well as meeting presentations and other sources. They identified 10 placebo-controlled, randomized clinical trials in which participants had atherosclerotic cardiovascular disease or ASCVD risk factors, diabetes, or heart failure. Among a total of 71,553 high-risk patients, 39,053 received an SGLT2 inhibitor and 32,500 received a placebo.

The primary outcome of cardiovascular death or hospitalization for heart failure occurred in 8.10% randomized to SGLT2 inhibitors, compared with 11.56% in the placebo group, a significant difference with odds ratio 0.67 (P < .001). Both individual outcomes were lower in the SGLT2-inhibitor group, with a number needed to treat of 5.7 (P < .001).

Patients receiving SGLT2 inhibitors also had significantly lower rates of major adverse cardiovascular events, defined as death due to cardiovascular causes, nonfatal MI, or nonfatal stroke. Those events occurred in 9.82% versus 10.22%(OR, 0.90; P = .03).

Hospitalizations and ED visits with heart failure were also reduced with SGLT2 inhibitors (4.37% vs. 6.81%; OR, 0.67; P < .001), as was cardiovascular death (4.65% vs. 5.14%; OR, 0.87; P = .009). The reduction in heart failure is likely caused by a combination of a natriuretic effect and reduced interstitial fluid, along with inhibition of cardiac fibrosis, the authors said.

On the other hand, no reductions were seen in acute MI, evaluated in five of the studies. That event occurred in 4.66% taking SGLT2 inhibitors, compared with 4.70% of the placebo group, a nonsignificant difference with an OR of 0.95 (P = 0.22). This is likely because of the fact that SGLT2 inhibitors don’t have known antianginal properties or vasodilatory effects, they don’t reduce myocardial oxygen consumption, and they don’t prevent cardiac muscle remodeling, they noted.

All-cause mortality was significantly lower with SGLT2 inhibitors, though, at 7.09% versus 7.86% (odds ratio, 0.87; P = .004).
 

Benefits seen across age, sex, and race/ethnicity subgroups

While no differences in benefit were found between men and women when compared with placebo groups, the rates of cardiovascular death or heart failure hospitalizations were slightly higher in men than in women (9.01% [OR, 0.75; P < .001] vs. 5.34% [OR, 0.78; P = .002]).

By age, SGLT2 inhibitors benefited people both those younger than 65 years and those aged 65 years and older, although the primary outcome was slightly lower in the younger group (6.94% [OR, 0.79; P < 0.001] vs. 10.47% [OR, 0.78; P < .001]).

And by race, similar benefits from SGLT2 inhibitors were seen among individuals who were White, compared with those who were Asian, Black, or of other race/ethnicity, with event rates of 8.77% (OR, 0.82; P < .001) and 8.75% (OR, 0.66; P = .06), respectively.

“Owing to the short-term trial durations, future long-term prospective studies and postmarketing surveillance studies are warranted to discover the rate of cardiovascular outcomes,” Dr. Bhattarai and colleagues concluded.

The authors have no disclosures.

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

Statins may be safe when used during pregnancy, with no increase in risk for fetal anomalies, although there may be a higher risk for low birth weight and preterm labor, results of a large study from Taiwan suggest.

The Food and Drug Administration relaxed its warning on statins in July 2021, removing the drug’s blanket contraindication in all pregnant women.

Removal of the broadly worded contraindication should “enable health care professionals and patients to make individual decisions about benefit and risk, especially for those at very high risk of heart attack or stroke,” the FDA said in their announcement.

“Our findings suggested that statins may be used during pregnancy with no increase in the rate of congenital anomalies,” wrote Jui-Chun Chang, MD, from Taichung Veterans General Hospital, Taiwan, and colleagues in the new study, published online Dec. 30, 2021, in JAMA Network Open.

“For pregnant women at low risk, statins should be used carefully after assessing the risks of low birth weight and preterm birth,” they said. “For women with dyslipidemia or high-risk cardiovascular disease, as well as those who use statins before conception, statins may be continuously used with no increased risks of neonatal adverse effects.”

The study included more than 1.4 million pregnant women aged 18 years and older who gave birth to their first child between 2004 and 2014.

A total of 469 women (mean age, 32.6 years; mean gestational age, 38.4 weeks) who used statins during pregnancy were compared with 4,690 matched controls who had no statin exposure during pregnancy.

After controlling for maternal comorbidities and age, women who used statins during pregnancy were more apt to have low-birth-weight babies weighing less than 2,500 g (risk ratio, 1.51; 95% confidence interval, 1.05-2.16) and to deliver preterm (RR, 1.99; 95% CI, 1.46-2.71).

The statin-exposed babies were also more likely to have a lower 1-minute Apgar score (RR, 1.83; 95% CI, 1.04-3.20). Importantly, however, there was no increase in risk for fetal anomalies in the statin-exposed infants, the researchers said.

In addition, for women who used statins for more than 3 months prior to pregnancy, maintaining statin use during pregnancy did not increase the risk for adverse neonatal outcomes, including congenital anomalies, low birth weight, preterm birth, very low birth weight, low Apgar scores, and fetal distress.

The researchers called for further studies to confirm their observations.

Funding for the study was provided by Taichung Veterans General Hospital. The authors have disclosed no relevant financial relationships.

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

Statins may be safe when used during pregnancy, with no increase in risk for fetal anomalies, although there may be a higher risk for low birth weight and preterm labor, results of a large study from Taiwan suggest.

The Food and Drug Administration relaxed its warning on statins in July 2021, removing the drug’s blanket contraindication in all pregnant women.

Removal of the broadly worded contraindication should “enable health care professionals and patients to make individual decisions about benefit and risk, especially for those at very high risk of heart attack or stroke,” the FDA said in their announcement.

“Our findings suggested that statins may be used during pregnancy with no increase in the rate of congenital anomalies,” wrote Jui-Chun Chang, MD, from Taichung Veterans General Hospital, Taiwan, and colleagues in the new study, published online Dec. 30, 2021, in JAMA Network Open.

“For pregnant women at low risk, statins should be used carefully after assessing the risks of low birth weight and preterm birth,” they said. “For women with dyslipidemia or high-risk cardiovascular disease, as well as those who use statins before conception, statins may be continuously used with no increased risks of neonatal adverse effects.”

The study included more than 1.4 million pregnant women aged 18 years and older who gave birth to their first child between 2004 and 2014.

A total of 469 women (mean age, 32.6 years; mean gestational age, 38.4 weeks) who used statins during pregnancy were compared with 4,690 matched controls who had no statin exposure during pregnancy.

After controlling for maternal comorbidities and age, women who used statins during pregnancy were more apt to have low-birth-weight babies weighing less than 2,500 g (risk ratio, 1.51; 95% confidence interval, 1.05-2.16) and to deliver preterm (RR, 1.99; 95% CI, 1.46-2.71).

The statin-exposed babies were also more likely to have a lower 1-minute Apgar score (RR, 1.83; 95% CI, 1.04-3.20). Importantly, however, there was no increase in risk for fetal anomalies in the statin-exposed infants, the researchers said.

In addition, for women who used statins for more than 3 months prior to pregnancy, maintaining statin use during pregnancy did not increase the risk for adverse neonatal outcomes, including congenital anomalies, low birth weight, preterm birth, very low birth weight, low Apgar scores, and fetal distress.

The researchers called for further studies to confirm their observations.

Funding for the study was provided by Taichung Veterans General Hospital. The authors have disclosed no relevant financial relationships.

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

Statins may be safe when used during pregnancy, with no increase in risk for fetal anomalies, although there may be a higher risk for low birth weight and preterm labor, results of a large study from Taiwan suggest.

The Food and Drug Administration relaxed its warning on statins in July 2021, removing the drug’s blanket contraindication in all pregnant women.

Removal of the broadly worded contraindication should “enable health care professionals and patients to make individual decisions about benefit and risk, especially for those at very high risk of heart attack or stroke,” the FDA said in their announcement.

“Our findings suggested that statins may be used during pregnancy with no increase in the rate of congenital anomalies,” wrote Jui-Chun Chang, MD, from Taichung Veterans General Hospital, Taiwan, and colleagues in the new study, published online Dec. 30, 2021, in JAMA Network Open.

“For pregnant women at low risk, statins should be used carefully after assessing the risks of low birth weight and preterm birth,” they said. “For women with dyslipidemia or high-risk cardiovascular disease, as well as those who use statins before conception, statins may be continuously used with no increased risks of neonatal adverse effects.”

The study included more than 1.4 million pregnant women aged 18 years and older who gave birth to their first child between 2004 and 2014.

A total of 469 women (mean age, 32.6 years; mean gestational age, 38.4 weeks) who used statins during pregnancy were compared with 4,690 matched controls who had no statin exposure during pregnancy.

After controlling for maternal comorbidities and age, women who used statins during pregnancy were more apt to have low-birth-weight babies weighing less than 2,500 g (risk ratio, 1.51; 95% confidence interval, 1.05-2.16) and to deliver preterm (RR, 1.99; 95% CI, 1.46-2.71).

The statin-exposed babies were also more likely to have a lower 1-minute Apgar score (RR, 1.83; 95% CI, 1.04-3.20). Importantly, however, there was no increase in risk for fetal anomalies in the statin-exposed infants, the researchers said.

In addition, for women who used statins for more than 3 months prior to pregnancy, maintaining statin use during pregnancy did not increase the risk for adverse neonatal outcomes, including congenital anomalies, low birth weight, preterm birth, very low birth weight, low Apgar scores, and fetal distress.

The researchers called for further studies to confirm their observations.

Funding for the study was provided by Taichung Veterans General Hospital. The authors have disclosed no relevant financial relationships.

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