User login
HFrEF mortality halved when treatment matches guidelines
PARIS – Heart failure patients who received guideline-directed pharmacotherapy, at dosages that approached guideline-directed levels, had roughly half the 6-month mortality as did similar patients who did not receive this level of treatment in a real-world, observational study with more than 6,000 patients.
Adherence to pharmacologic treatment guidelines for patients with heart failure with reduced ejection fraction (HFrEF) “was strongly associated with clinical outcomes during 6-month follow-up,” Michel Komajda, MD, said at a meeting held by the Heart Failure Association of the European Society of Cardiology. The findings highlight the importance of closely following guideline recommendations in routine practice.
[polldaddy:9772629]
The analysis used data collected in the QUALIFY (Quality of Adherence to Guideline Recommendations for Life-Saving Treatment in Heart Failure: an International Survey) registry, which enrolled 7,127 HFrEF patients during September 2013–December 2014 at 547 centers in 36 countries, mostly in Europe, Asia, and Africa but also in Canada, Ecuador, and Australia. All enrolled patients had to have been hospitalized for worsening heart failure at least once during the 1-15 months before they entered QUALIFY.
Dr. Komajda and his associates assessed each enrolled patient at baseline by their treatment with each of four guideline-recommended drug classes: an ACE inhibitor or angiotensin receptor blocker; a beta-blocker; an aldosterone receptor antagonist (ARA) if the patient’s functional status was rated as New York Heart Association class II, III, or IV; and ivabradine (Corlanor) if the patient was in NYHA class II, III, or IV, in sinus rhythm, had a heart rate of at least 70 beats per minute, and if the patient was in a country where ivabradine was available. Because patient enrollment occurred in 2013 and 2014, the study couldn’t include the new formulation of sacubitril plus valsartan (Entresto) in its analysis.
For each eligible drug class a patient received 1 point if their daily prescribed dosage was at least 50% of the recommended dosage (or 100% for an ARA), 0.5 points if the patient received the recommended drug but at a lower dosage, and no points if the drug wasn’t given. A patient also received 1 point if they were appropriately not given a drug because of a documented contraindication or intolerance. The researchers then calculated each patient’s “adherence score” by dividing their point total by the potentially maximum number of points that each patient could have received (a number that ranged from 2 to 4). They defined a score of 1 (which meant the patients received at least half the recommended dosage of all recommended drugs) as good adherence, a score of 0.51-0.99 as moderate adherence, and a score of 0.5 or less as poor adherence.
Because patient enrollment occurred during 2013 and 2014, the benchmark heart failure treatment guidelines were those issued by the European Society of Cardiology in 2012 (Eur Heart J. 2012 July;33[14]:1787-1847).
Concurrently with Dr. Komajda’s report at the meeting the results appeared in an article online (Eur J Heart Failure. 2017. doi: 10.1002/ejhf.887).
QUANTIFY was sponsored by Servier. Dr. Komajda has received honoraria from Servier and from Amgen, AstraZeneca, Bristol-Myers Squibb, Menarini, MSD, Novartis, Novo Nordisk, and Sanofi.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
This was a wonderful and useful study. It was large, prospective, covered a wide geographic area, and showed that drug dosage matters when treating heart failure with reduced ejection fraction.
The geographic diversity was a strength, but also a potential weakness because of the resulting differences among the enrolled patients in financial resources, ethnic and genetic makeup, and their tolerance to various drugs. I hope that further research can dissect the role that each of these factors played in the results.
Another limitation is the relatively simplistic approach used for assessing drug dosages to calculate the adherence scores. While it is a very useful step forward to classify patients by the drug dosages they received, there could be some very legitimate variations in dosages based on parameters such as blood pressure. An important question to address in the future is whether it is better to use all the recommended drugs at reduced dosages if necessary, or to use fewer agents at higher dosages.
But these are just quibbles about what is a very important study.
Andrew J.S. Coats, MD , is a cardiologist, professor of medicine, and academic vice-president for the Monash Warwick Alliance of Warwick University in Coventry, England, and Monash University in Melbourne. He has received honoraria from Impulse Dynamics, Menarini, PsiOxus, ResMed, Respicardia, and Servier. He made these comments as designated discussant for Dr. Komajda’s report.
This was a wonderful and useful study. It was large, prospective, covered a wide geographic area, and showed that drug dosage matters when treating heart failure with reduced ejection fraction.
The geographic diversity was a strength, but also a potential weakness because of the resulting differences among the enrolled patients in financial resources, ethnic and genetic makeup, and their tolerance to various drugs. I hope that further research can dissect the role that each of these factors played in the results.
Another limitation is the relatively simplistic approach used for assessing drug dosages to calculate the adherence scores. While it is a very useful step forward to classify patients by the drug dosages they received, there could be some very legitimate variations in dosages based on parameters such as blood pressure. An important question to address in the future is whether it is better to use all the recommended drugs at reduced dosages if necessary, or to use fewer agents at higher dosages.
But these are just quibbles about what is a very important study.
Andrew J.S. Coats, MD , is a cardiologist, professor of medicine, and academic vice-president for the Monash Warwick Alliance of Warwick University in Coventry, England, and Monash University in Melbourne. He has received honoraria from Impulse Dynamics, Menarini, PsiOxus, ResMed, Respicardia, and Servier. He made these comments as designated discussant for Dr. Komajda’s report.
This was a wonderful and useful study. It was large, prospective, covered a wide geographic area, and showed that drug dosage matters when treating heart failure with reduced ejection fraction.
The geographic diversity was a strength, but also a potential weakness because of the resulting differences among the enrolled patients in financial resources, ethnic and genetic makeup, and their tolerance to various drugs. I hope that further research can dissect the role that each of these factors played in the results.
Another limitation is the relatively simplistic approach used for assessing drug dosages to calculate the adherence scores. While it is a very useful step forward to classify patients by the drug dosages they received, there could be some very legitimate variations in dosages based on parameters such as blood pressure. An important question to address in the future is whether it is better to use all the recommended drugs at reduced dosages if necessary, or to use fewer agents at higher dosages.
But these are just quibbles about what is a very important study.
Andrew J.S. Coats, MD , is a cardiologist, professor of medicine, and academic vice-president for the Monash Warwick Alliance of Warwick University in Coventry, England, and Monash University in Melbourne. He has received honoraria from Impulse Dynamics, Menarini, PsiOxus, ResMed, Respicardia, and Servier. He made these comments as designated discussant for Dr. Komajda’s report.
PARIS – Heart failure patients who received guideline-directed pharmacotherapy, at dosages that approached guideline-directed levels, had roughly half the 6-month mortality as did similar patients who did not receive this level of treatment in a real-world, observational study with more than 6,000 patients.
Adherence to pharmacologic treatment guidelines for patients with heart failure with reduced ejection fraction (HFrEF) “was strongly associated with clinical outcomes during 6-month follow-up,” Michel Komajda, MD, said at a meeting held by the Heart Failure Association of the European Society of Cardiology. The findings highlight the importance of closely following guideline recommendations in routine practice.
[polldaddy:9772629]
The analysis used data collected in the QUALIFY (Quality of Adherence to Guideline Recommendations for Life-Saving Treatment in Heart Failure: an International Survey) registry, which enrolled 7,127 HFrEF patients during September 2013–December 2014 at 547 centers in 36 countries, mostly in Europe, Asia, and Africa but also in Canada, Ecuador, and Australia. All enrolled patients had to have been hospitalized for worsening heart failure at least once during the 1-15 months before they entered QUALIFY.
Dr. Komajda and his associates assessed each enrolled patient at baseline by their treatment with each of four guideline-recommended drug classes: an ACE inhibitor or angiotensin receptor blocker; a beta-blocker; an aldosterone receptor antagonist (ARA) if the patient’s functional status was rated as New York Heart Association class II, III, or IV; and ivabradine (Corlanor) if the patient was in NYHA class II, III, or IV, in sinus rhythm, had a heart rate of at least 70 beats per minute, and if the patient was in a country where ivabradine was available. Because patient enrollment occurred in 2013 and 2014, the study couldn’t include the new formulation of sacubitril plus valsartan (Entresto) in its analysis.
For each eligible drug class a patient received 1 point if their daily prescribed dosage was at least 50% of the recommended dosage (or 100% for an ARA), 0.5 points if the patient received the recommended drug but at a lower dosage, and no points if the drug wasn’t given. A patient also received 1 point if they were appropriately not given a drug because of a documented contraindication or intolerance. The researchers then calculated each patient’s “adherence score” by dividing their point total by the potentially maximum number of points that each patient could have received (a number that ranged from 2 to 4). They defined a score of 1 (which meant the patients received at least half the recommended dosage of all recommended drugs) as good adherence, a score of 0.51-0.99 as moderate adherence, and a score of 0.5 or less as poor adherence.
Because patient enrollment occurred during 2013 and 2014, the benchmark heart failure treatment guidelines were those issued by the European Society of Cardiology in 2012 (Eur Heart J. 2012 July;33[14]:1787-1847).
Concurrently with Dr. Komajda’s report at the meeting the results appeared in an article online (Eur J Heart Failure. 2017. doi: 10.1002/ejhf.887).
QUANTIFY was sponsored by Servier. Dr. Komajda has received honoraria from Servier and from Amgen, AstraZeneca, Bristol-Myers Squibb, Menarini, MSD, Novartis, Novo Nordisk, and Sanofi.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
PARIS – Heart failure patients who received guideline-directed pharmacotherapy, at dosages that approached guideline-directed levels, had roughly half the 6-month mortality as did similar patients who did not receive this level of treatment in a real-world, observational study with more than 6,000 patients.
Adherence to pharmacologic treatment guidelines for patients with heart failure with reduced ejection fraction (HFrEF) “was strongly associated with clinical outcomes during 6-month follow-up,” Michel Komajda, MD, said at a meeting held by the Heart Failure Association of the European Society of Cardiology. The findings highlight the importance of closely following guideline recommendations in routine practice.
[polldaddy:9772629]
The analysis used data collected in the QUALIFY (Quality of Adherence to Guideline Recommendations for Life-Saving Treatment in Heart Failure: an International Survey) registry, which enrolled 7,127 HFrEF patients during September 2013–December 2014 at 547 centers in 36 countries, mostly in Europe, Asia, and Africa but also in Canada, Ecuador, and Australia. All enrolled patients had to have been hospitalized for worsening heart failure at least once during the 1-15 months before they entered QUALIFY.
Dr. Komajda and his associates assessed each enrolled patient at baseline by their treatment with each of four guideline-recommended drug classes: an ACE inhibitor or angiotensin receptor blocker; a beta-blocker; an aldosterone receptor antagonist (ARA) if the patient’s functional status was rated as New York Heart Association class II, III, or IV; and ivabradine (Corlanor) if the patient was in NYHA class II, III, or IV, in sinus rhythm, had a heart rate of at least 70 beats per minute, and if the patient was in a country where ivabradine was available. Because patient enrollment occurred in 2013 and 2014, the study couldn’t include the new formulation of sacubitril plus valsartan (Entresto) in its analysis.
For each eligible drug class a patient received 1 point if their daily prescribed dosage was at least 50% of the recommended dosage (or 100% for an ARA), 0.5 points if the patient received the recommended drug but at a lower dosage, and no points if the drug wasn’t given. A patient also received 1 point if they were appropriately not given a drug because of a documented contraindication or intolerance. The researchers then calculated each patient’s “adherence score” by dividing their point total by the potentially maximum number of points that each patient could have received (a number that ranged from 2 to 4). They defined a score of 1 (which meant the patients received at least half the recommended dosage of all recommended drugs) as good adherence, a score of 0.51-0.99 as moderate adherence, and a score of 0.5 or less as poor adherence.
Because patient enrollment occurred during 2013 and 2014, the benchmark heart failure treatment guidelines were those issued by the European Society of Cardiology in 2012 (Eur Heart J. 2012 July;33[14]:1787-1847).
Concurrently with Dr. Komajda’s report at the meeting the results appeared in an article online (Eur J Heart Failure. 2017. doi: 10.1002/ejhf.887).
QUANTIFY was sponsored by Servier. Dr. Komajda has received honoraria from Servier and from Amgen, AstraZeneca, Bristol-Myers Squibb, Menarini, MSD, Novartis, Novo Nordisk, and Sanofi.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
AT HEART FAILURE 2017
Key clinical point:
Major finding: Six-month all-cause, cardiovascular, and heart failure mortalities were doubled in patients not on guideline-adherent therapy and dosages.
Data source: QUANTIFY, an international registry with 6,669 HFrEF patients followed for 6 months.
Disclosures: QUANTIFY was sponsored by Servier. Dr. Komajda has received honoraria from Servier and from Amgen, AstraZeneca, Bristol-Myers Squibb, Menarini, MSD, Novartis, Novo Nordisk, and Sanofi.
Angiotensin II may improve vasopressors’ efficacy
WASHINGTON – Adding angiotensin II to available vasopressor therapies correlated with significantly improved arterial pressure in patients with catecholamine-resistant vasodilatory shock and less adverse effects, according to a study presented at the recent international conference of the American Thoracic Society.
In a double blind, controlled, phase III study, 70% of 163 patients given angiotensin II reached arterial pressure of at least 75 mm HG or improved by at least 10 mm Hg three hours later, compared with 23.4% of the 158 patients given a placebo (P less than .001).
Those in the angiotensin II group also saw a mean pressure increase of 12.5 mm Hg in the first 3 hours after initiating treatment, compared with 2.9 mm Hg in the placebo group (P less than .001), according to Ashish Khanna, MD, FCCP, of the Cleveland Clinic, and his fellow researchers (N Engl J Med. 2017 May 21. doi: 10.1056/NEJMoa1704154).
Current vasopressor therapies for vasodilatory patients are associated with dangerous side effects and a 30-day mortality rate of more than 50%, which is a major concern for patients who do not have many options to begin with, the researchers noted.
“Treatment options for patients with catecholamine-resistant vasodilatory shock are limited, and the treatments that are available are often associated with side effects,” said Dr. Khanna and his colleagues.
The researchers added the naturally occurring peptide hormone angiotensin II to vasodilatory patients’ treatment regimen in order to “more closely [mimic] natural physiologic responses to shock, which include increased secretion of catecholamines, vasopressin, and RAAS hormones.”
To test the efficacy of angiotensin II, researchers gathered patients with a median age of 64 years and a mean arterial pressure of 66.3 mm Hg.
Sepsis was the predominant cause of shock for 80.7% of the study’s participants.
Patients were injected with either 20 ng/kg of body weight per minute of angiotensin II or an equivalent dose of a placebo until mean arterial pressure reached 75 mm Hg. After 3 hours and 15 minutes of treatment, the dosages were adjusted to keep pressure between 65 and 75 mm Hg for the next 48 hours.
Among patients in the angiotensin II group, 67% of patients were able to decrease angiotensin II and vasopressor doses within 30 minutes of injection, according to researchers.
When researchers measured improvement using the cardiovascular Sequential Organ Failure Assessment, patients in the angiotensin II group saw an average decrease of 1.75 points, compared with 1.28 points in patients in the placebo group (P = .01) 48 hours after treatment.
The Sequential Organ Failure Assessment is scaled from 0-4, with higher scores indicating more severe organ failure.
When measuring for adverse affects, serious effects occurred in 60.7% of the angiotensin II patients, compared with in 67.1% of those in the placebo group.
At the 28-day mark, 75 angiotensin II patients (46.0%) died, compared with 85 patients (53.8%) of the placebo group.
This study was limited by the small sample size, “so the possibility of clinically important side effects attributable to angiotensin II therapy cannot be exuded,” the researches warned.
Also, the follow-up timeline of 28 days, may not have given researchers enough time to uncover the full extent of positive and negative long-term effects associated with angiotensin II.
This study was supported by La Jolla Pharmaceutical, from which multiple researchers reported receiving financial support in the form of personal fees and grants. Two of the researchers reported having patents related to administering angiotensin II and additional patents pending.
ezimmerman@frontlinemedcom.com
On Twitter @eaztweets
WASHINGTON – Adding angiotensin II to available vasopressor therapies correlated with significantly improved arterial pressure in patients with catecholamine-resistant vasodilatory shock and less adverse effects, according to a study presented at the recent international conference of the American Thoracic Society.
In a double blind, controlled, phase III study, 70% of 163 patients given angiotensin II reached arterial pressure of at least 75 mm HG or improved by at least 10 mm Hg three hours later, compared with 23.4% of the 158 patients given a placebo (P less than .001).
Those in the angiotensin II group also saw a mean pressure increase of 12.5 mm Hg in the first 3 hours after initiating treatment, compared with 2.9 mm Hg in the placebo group (P less than .001), according to Ashish Khanna, MD, FCCP, of the Cleveland Clinic, and his fellow researchers (N Engl J Med. 2017 May 21. doi: 10.1056/NEJMoa1704154).
Current vasopressor therapies for vasodilatory patients are associated with dangerous side effects and a 30-day mortality rate of more than 50%, which is a major concern for patients who do not have many options to begin with, the researchers noted.
“Treatment options for patients with catecholamine-resistant vasodilatory shock are limited, and the treatments that are available are often associated with side effects,” said Dr. Khanna and his colleagues.
The researchers added the naturally occurring peptide hormone angiotensin II to vasodilatory patients’ treatment regimen in order to “more closely [mimic] natural physiologic responses to shock, which include increased secretion of catecholamines, vasopressin, and RAAS hormones.”
To test the efficacy of angiotensin II, researchers gathered patients with a median age of 64 years and a mean arterial pressure of 66.3 mm Hg.
Sepsis was the predominant cause of shock for 80.7% of the study’s participants.
Patients were injected with either 20 ng/kg of body weight per minute of angiotensin II or an equivalent dose of a placebo until mean arterial pressure reached 75 mm Hg. After 3 hours and 15 minutes of treatment, the dosages were adjusted to keep pressure between 65 and 75 mm Hg for the next 48 hours.
Among patients in the angiotensin II group, 67% of patients were able to decrease angiotensin II and vasopressor doses within 30 minutes of injection, according to researchers.
When researchers measured improvement using the cardiovascular Sequential Organ Failure Assessment, patients in the angiotensin II group saw an average decrease of 1.75 points, compared with 1.28 points in patients in the placebo group (P = .01) 48 hours after treatment.
The Sequential Organ Failure Assessment is scaled from 0-4, with higher scores indicating more severe organ failure.
When measuring for adverse affects, serious effects occurred in 60.7% of the angiotensin II patients, compared with in 67.1% of those in the placebo group.
At the 28-day mark, 75 angiotensin II patients (46.0%) died, compared with 85 patients (53.8%) of the placebo group.
This study was limited by the small sample size, “so the possibility of clinically important side effects attributable to angiotensin II therapy cannot be exuded,” the researches warned.
Also, the follow-up timeline of 28 days, may not have given researchers enough time to uncover the full extent of positive and negative long-term effects associated with angiotensin II.
This study was supported by La Jolla Pharmaceutical, from which multiple researchers reported receiving financial support in the form of personal fees and grants. Two of the researchers reported having patents related to administering angiotensin II and additional patents pending.
ezimmerman@frontlinemedcom.com
On Twitter @eaztweets
WASHINGTON – Adding angiotensin II to available vasopressor therapies correlated with significantly improved arterial pressure in patients with catecholamine-resistant vasodilatory shock and less adverse effects, according to a study presented at the recent international conference of the American Thoracic Society.
In a double blind, controlled, phase III study, 70% of 163 patients given angiotensin II reached arterial pressure of at least 75 mm HG or improved by at least 10 mm Hg three hours later, compared with 23.4% of the 158 patients given a placebo (P less than .001).
Those in the angiotensin II group also saw a mean pressure increase of 12.5 mm Hg in the first 3 hours after initiating treatment, compared with 2.9 mm Hg in the placebo group (P less than .001), according to Ashish Khanna, MD, FCCP, of the Cleveland Clinic, and his fellow researchers (N Engl J Med. 2017 May 21. doi: 10.1056/NEJMoa1704154).
Current vasopressor therapies for vasodilatory patients are associated with dangerous side effects and a 30-day mortality rate of more than 50%, which is a major concern for patients who do not have many options to begin with, the researchers noted.
“Treatment options for patients with catecholamine-resistant vasodilatory shock are limited, and the treatments that are available are often associated with side effects,” said Dr. Khanna and his colleagues.
The researchers added the naturally occurring peptide hormone angiotensin II to vasodilatory patients’ treatment regimen in order to “more closely [mimic] natural physiologic responses to shock, which include increased secretion of catecholamines, vasopressin, and RAAS hormones.”
To test the efficacy of angiotensin II, researchers gathered patients with a median age of 64 years and a mean arterial pressure of 66.3 mm Hg.
Sepsis was the predominant cause of shock for 80.7% of the study’s participants.
Patients were injected with either 20 ng/kg of body weight per minute of angiotensin II or an equivalent dose of a placebo until mean arterial pressure reached 75 mm Hg. After 3 hours and 15 minutes of treatment, the dosages were adjusted to keep pressure between 65 and 75 mm Hg for the next 48 hours.
Among patients in the angiotensin II group, 67% of patients were able to decrease angiotensin II and vasopressor doses within 30 minutes of injection, according to researchers.
When researchers measured improvement using the cardiovascular Sequential Organ Failure Assessment, patients in the angiotensin II group saw an average decrease of 1.75 points, compared with 1.28 points in patients in the placebo group (P = .01) 48 hours after treatment.
The Sequential Organ Failure Assessment is scaled from 0-4, with higher scores indicating more severe organ failure.
When measuring for adverse affects, serious effects occurred in 60.7% of the angiotensin II patients, compared with in 67.1% of those in the placebo group.
At the 28-day mark, 75 angiotensin II patients (46.0%) died, compared with 85 patients (53.8%) of the placebo group.
This study was limited by the small sample size, “so the possibility of clinically important side effects attributable to angiotensin II therapy cannot be exuded,” the researches warned.
Also, the follow-up timeline of 28 days, may not have given researchers enough time to uncover the full extent of positive and negative long-term effects associated with angiotensin II.
This study was supported by La Jolla Pharmaceutical, from which multiple researchers reported receiving financial support in the form of personal fees and grants. Two of the researchers reported having patents related to administering angiotensin II and additional patents pending.
ezimmerman@frontlinemedcom.com
On Twitter @eaztweets
At ATS 2017
Key clinical point:
Major finding: In the first 3 hours, patients taking angiotensin II improved arterial pressure by an average of 12.5 mm Hg, compared with 2.9 mm Hg in patients taking the placebo (P less than .001)
Data source: Double blind, randomized, control trial of 321 patients with catecholamine-resistant vasodilatory shock collected from 75 intensive care units globally during May 2015-January 2017.
Disclosures: Multiple investigators reported receiving support from La Jolla Pharmaceutical and similar companies in the form of grants and/or personal fees. Two of the researchers reported having patents related to administering angiotensin II and additional patents pending.
Atrial fibrillation blunts beta-blockers for HFrEF
PARIS – Maximal beta-blocker treatment and lower heart rates are effective at cutting all-cause mortality in patients with heart failure with reduced ejection fraction (HFrEF) who are also in sinus rhythm, but it’s a totally different story for patients with similar heart failure plus atrial fibrillation. In the atrial fibrillation subgroup, treatment with a beta-blocker linked with no mortality benefit, and lower heart rates – below 70 beats per minute – appeared to actually link with worse patient survival, based on a meta-analysis of data from 11 beta-blocker trials with a total of more than 17,000 patients.
“Beta blockers may be doing good in heart failure patients with atrial fibrillation, but they also are doing harm that neutralizes any good they do.” In patients with HFrEF and atrial fibrillation, “I don’t like to see the heart rate below 80 beats per minute,” John G.F. Cleland, MD, said at a meeting held by the Heart Failure Association of the ESC.
“We’ve perhaps been too aggressive with heart-rate control in HFrEF patients with atrial fibrillation,” he added in an interview. In these patients “in the range of 60-100 bpm it doesn’t seem to make a lot of difference what the heart rate is, and, if it is less than 70 bpm, patients seem to do a little worse. When we treat these patients with a beta-blocker we don’t see benefit in any way that we’ve looked at the data.”
In contrast, among HFrEF patients in sinus rhythm “beta-blocker treatment is similarly effective regardless of what the baseline heart rate was. The benefit was as great when the baseline rate was 70 bpm or 90 bpm, so heart rate is not a great predictor of beta-blocker benefit in these patients. Patients who tolerated the full beta-blocker dosage had the greatest benefit, and patients who achieved the slowest heart rates also had the greatest benefit.”
In the multivariate models that Dr. Cleland and his associates tested in their meta-analysis, in HFrEF patients in sinus rhythm, the relationship between reduced heart rate and mortality benefit was stronger statistically than between beta-blocker dosage and reduced mortality, he said. “This suggests to me that, while we should use the targeted beta-blocker dosages when we can, it’s more important to achieve a target heart rate in these patients of 55-65 bpm.”
Dr. Cleland hypothesized, based on a report presented at the same meeting by a different research group, that reduced heart rate is not beneficial in HFrEF patients with atrial fibrillation because in this subgroup slower heart rates linked with an increased number of brief pauses in left ventricular pumping. These pauses may result in ventricular arrhythmias, he speculated. “It may be that beta-blockers are equally effective at slowing heart rate in patients with or without atrial fibrillation, but there is also harm from beta-blockers because they’re causing pauses in patients with atrial fibrillation,” he said.
These days, if he has a HFrEF patient with atrial fibrillation whose heart rate slows to 60 bpm, he will stop digoxin treatment if the patient is on that drug, and he will also reduce the beta-blocker dosage but not discontinue it.
The findings came from the Collaborative Systematic Overview of Randomized Controlled Trials of Beta-Blockers in the Treatment of Heart Failure (BB-META-HF), which included data from 11 large beta-blocker randomized trials in heart failure that had been published during 1993-2005. The analysis included data from 17,378 HFrEF patients, with 14,313 (82%) in sinus rhythm and 3,065 (18%) with atrial fibrillation. Follow-up data of patients on treatment was available for 15,007 of these patients.
Dr. Cleland and his associates showed in multivariate analyses that, when they controlled for several baseline demographic and clinical variables among patients in sinus rhythm who received a beta-blocker, the follow-up all-cause mortality fell by 36%, compared with placebo, in patients with a resting baseline heart rate of less than 70 bpm; by 21%, compared with placebo, in patients with a baseline heart rate of 70-90 bpm; and by 38%, compared with placebo, in patients with a baseline heart rate of more than 90 bpm. All three reductions were statistically significant. In contrast, among patients who also had atrial fibrillation beta-blocker treatment linked with no significant mortality reduction, compared with placebo, for patients with any baseline heart rate. Concurrently with Dr. Cleland’s report at the meeting the results appeared online (J Amer Coll Cardiol. 2017 Apr 30. doi: 10.1016/j.jacc.2017.04.001).
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
The findings from this analysis have several implications. First, the association of reduced mortality with reduced heart rate occurred only in patients in sinus rhythm. The irregular heart rhythms in patients with atrial fibrillation may counterbalance any reverse remodeling effects that come from reducing heart rate.
Also, the beneficial effect of beta-blocker treatment was roughly similar regardless of whether baseline heart rate was high or low. This distinguishes beta-blockers from ivabradine, a drug that only reduces heart rate. The magnitude of benefit from ivabradine treatment depends on a patient’s baseline heart rate. The observation that beta-blockers do not have the same limitation suggests that the mechanism of action of beta-blockers may go beyond their heart rate effect. It may also result from the effect of beta-blockers on antagonizing toxic effects from beta-adrenergic stimulation.
The pooled analysis also showed that many patients with HFrEF in sinus rhythm continued to have a high heart rate despite beta-blocker treatment. These patients may get additional benefit from further treatment to reduce their heart rate, with an agent like ivabradine.
But we must be cautious in interpreting the findings because they represent a secondary analysis, and the endpoint studied does not take into account quality of life, exercise tolerance, heart rate control, and tachyarrhythmias. We need prospective, randomized trials of HFrEF patients in sinus rhythm and with atrial fibrillation to better understand how to optimally treat these different types of patients.
The findings highlight that beta-blockers remain a mainstay of treatment for patients with HFrEF in sinus rhythm, and that we have more limited treatment options for HFrEF patients with atrial fibrillation.
Michael Böhm, MD, is professor and director of the cardiology clinic at Saarland University Hospital in Homburg, Germany. He has received honoraria from Bayer, Medtronic, Servier, and Pfizer, and he was a coauthor on the report presented by Dr. Cleland. He made these comments as designated discussant for the study.
The findings from this analysis have several implications. First, the association of reduced mortality with reduced heart rate occurred only in patients in sinus rhythm. The irregular heart rhythms in patients with atrial fibrillation may counterbalance any reverse remodeling effects that come from reducing heart rate.
Also, the beneficial effect of beta-blocker treatment was roughly similar regardless of whether baseline heart rate was high or low. This distinguishes beta-blockers from ivabradine, a drug that only reduces heart rate. The magnitude of benefit from ivabradine treatment depends on a patient’s baseline heart rate. The observation that beta-blockers do not have the same limitation suggests that the mechanism of action of beta-blockers may go beyond their heart rate effect. It may also result from the effect of beta-blockers on antagonizing toxic effects from beta-adrenergic stimulation.
The pooled analysis also showed that many patients with HFrEF in sinus rhythm continued to have a high heart rate despite beta-blocker treatment. These patients may get additional benefit from further treatment to reduce their heart rate, with an agent like ivabradine.
But we must be cautious in interpreting the findings because they represent a secondary analysis, and the endpoint studied does not take into account quality of life, exercise tolerance, heart rate control, and tachyarrhythmias. We need prospective, randomized trials of HFrEF patients in sinus rhythm and with atrial fibrillation to better understand how to optimally treat these different types of patients.
The findings highlight that beta-blockers remain a mainstay of treatment for patients with HFrEF in sinus rhythm, and that we have more limited treatment options for HFrEF patients with atrial fibrillation.
Michael Böhm, MD, is professor and director of the cardiology clinic at Saarland University Hospital in Homburg, Germany. He has received honoraria from Bayer, Medtronic, Servier, and Pfizer, and he was a coauthor on the report presented by Dr. Cleland. He made these comments as designated discussant for the study.
The findings from this analysis have several implications. First, the association of reduced mortality with reduced heart rate occurred only in patients in sinus rhythm. The irregular heart rhythms in patients with atrial fibrillation may counterbalance any reverse remodeling effects that come from reducing heart rate.
Also, the beneficial effect of beta-blocker treatment was roughly similar regardless of whether baseline heart rate was high or low. This distinguishes beta-blockers from ivabradine, a drug that only reduces heart rate. The magnitude of benefit from ivabradine treatment depends on a patient’s baseline heart rate. The observation that beta-blockers do not have the same limitation suggests that the mechanism of action of beta-blockers may go beyond their heart rate effect. It may also result from the effect of beta-blockers on antagonizing toxic effects from beta-adrenergic stimulation.
The pooled analysis also showed that many patients with HFrEF in sinus rhythm continued to have a high heart rate despite beta-blocker treatment. These patients may get additional benefit from further treatment to reduce their heart rate, with an agent like ivabradine.
But we must be cautious in interpreting the findings because they represent a secondary analysis, and the endpoint studied does not take into account quality of life, exercise tolerance, heart rate control, and tachyarrhythmias. We need prospective, randomized trials of HFrEF patients in sinus rhythm and with atrial fibrillation to better understand how to optimally treat these different types of patients.
The findings highlight that beta-blockers remain a mainstay of treatment for patients with HFrEF in sinus rhythm, and that we have more limited treatment options for HFrEF patients with atrial fibrillation.
Michael Böhm, MD, is professor and director of the cardiology clinic at Saarland University Hospital in Homburg, Germany. He has received honoraria from Bayer, Medtronic, Servier, and Pfizer, and he was a coauthor on the report presented by Dr. Cleland. He made these comments as designated discussant for the study.
PARIS – Maximal beta-blocker treatment and lower heart rates are effective at cutting all-cause mortality in patients with heart failure with reduced ejection fraction (HFrEF) who are also in sinus rhythm, but it’s a totally different story for patients with similar heart failure plus atrial fibrillation. In the atrial fibrillation subgroup, treatment with a beta-blocker linked with no mortality benefit, and lower heart rates – below 70 beats per minute – appeared to actually link with worse patient survival, based on a meta-analysis of data from 11 beta-blocker trials with a total of more than 17,000 patients.
“Beta blockers may be doing good in heart failure patients with atrial fibrillation, but they also are doing harm that neutralizes any good they do.” In patients with HFrEF and atrial fibrillation, “I don’t like to see the heart rate below 80 beats per minute,” John G.F. Cleland, MD, said at a meeting held by the Heart Failure Association of the ESC.
“We’ve perhaps been too aggressive with heart-rate control in HFrEF patients with atrial fibrillation,” he added in an interview. In these patients “in the range of 60-100 bpm it doesn’t seem to make a lot of difference what the heart rate is, and, if it is less than 70 bpm, patients seem to do a little worse. When we treat these patients with a beta-blocker we don’t see benefit in any way that we’ve looked at the data.”
In contrast, among HFrEF patients in sinus rhythm “beta-blocker treatment is similarly effective regardless of what the baseline heart rate was. The benefit was as great when the baseline rate was 70 bpm or 90 bpm, so heart rate is not a great predictor of beta-blocker benefit in these patients. Patients who tolerated the full beta-blocker dosage had the greatest benefit, and patients who achieved the slowest heart rates also had the greatest benefit.”
In the multivariate models that Dr. Cleland and his associates tested in their meta-analysis, in HFrEF patients in sinus rhythm, the relationship between reduced heart rate and mortality benefit was stronger statistically than between beta-blocker dosage and reduced mortality, he said. “This suggests to me that, while we should use the targeted beta-blocker dosages when we can, it’s more important to achieve a target heart rate in these patients of 55-65 bpm.”
Dr. Cleland hypothesized, based on a report presented at the same meeting by a different research group, that reduced heart rate is not beneficial in HFrEF patients with atrial fibrillation because in this subgroup slower heart rates linked with an increased number of brief pauses in left ventricular pumping. These pauses may result in ventricular arrhythmias, he speculated. “It may be that beta-blockers are equally effective at slowing heart rate in patients with or without atrial fibrillation, but there is also harm from beta-blockers because they’re causing pauses in patients with atrial fibrillation,” he said.
These days, if he has a HFrEF patient with atrial fibrillation whose heart rate slows to 60 bpm, he will stop digoxin treatment if the patient is on that drug, and he will also reduce the beta-blocker dosage but not discontinue it.
The findings came from the Collaborative Systematic Overview of Randomized Controlled Trials of Beta-Blockers in the Treatment of Heart Failure (BB-META-HF), which included data from 11 large beta-blocker randomized trials in heart failure that had been published during 1993-2005. The analysis included data from 17,378 HFrEF patients, with 14,313 (82%) in sinus rhythm and 3,065 (18%) with atrial fibrillation. Follow-up data of patients on treatment was available for 15,007 of these patients.
Dr. Cleland and his associates showed in multivariate analyses that, when they controlled for several baseline demographic and clinical variables among patients in sinus rhythm who received a beta-blocker, the follow-up all-cause mortality fell by 36%, compared with placebo, in patients with a resting baseline heart rate of less than 70 bpm; by 21%, compared with placebo, in patients with a baseline heart rate of 70-90 bpm; and by 38%, compared with placebo, in patients with a baseline heart rate of more than 90 bpm. All three reductions were statistically significant. In contrast, among patients who also had atrial fibrillation beta-blocker treatment linked with no significant mortality reduction, compared with placebo, for patients with any baseline heart rate. Concurrently with Dr. Cleland’s report at the meeting the results appeared online (J Amer Coll Cardiol. 2017 Apr 30. doi: 10.1016/j.jacc.2017.04.001).
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
PARIS – Maximal beta-blocker treatment and lower heart rates are effective at cutting all-cause mortality in patients with heart failure with reduced ejection fraction (HFrEF) who are also in sinus rhythm, but it’s a totally different story for patients with similar heart failure plus atrial fibrillation. In the atrial fibrillation subgroup, treatment with a beta-blocker linked with no mortality benefit, and lower heart rates – below 70 beats per minute – appeared to actually link with worse patient survival, based on a meta-analysis of data from 11 beta-blocker trials with a total of more than 17,000 patients.
“Beta blockers may be doing good in heart failure patients with atrial fibrillation, but they also are doing harm that neutralizes any good they do.” In patients with HFrEF and atrial fibrillation, “I don’t like to see the heart rate below 80 beats per minute,” John G.F. Cleland, MD, said at a meeting held by the Heart Failure Association of the ESC.
“We’ve perhaps been too aggressive with heart-rate control in HFrEF patients with atrial fibrillation,” he added in an interview. In these patients “in the range of 60-100 bpm it doesn’t seem to make a lot of difference what the heart rate is, and, if it is less than 70 bpm, patients seem to do a little worse. When we treat these patients with a beta-blocker we don’t see benefit in any way that we’ve looked at the data.”
In contrast, among HFrEF patients in sinus rhythm “beta-blocker treatment is similarly effective regardless of what the baseline heart rate was. The benefit was as great when the baseline rate was 70 bpm or 90 bpm, so heart rate is not a great predictor of beta-blocker benefit in these patients. Patients who tolerated the full beta-blocker dosage had the greatest benefit, and patients who achieved the slowest heart rates also had the greatest benefit.”
In the multivariate models that Dr. Cleland and his associates tested in their meta-analysis, in HFrEF patients in sinus rhythm, the relationship between reduced heart rate and mortality benefit was stronger statistically than between beta-blocker dosage and reduced mortality, he said. “This suggests to me that, while we should use the targeted beta-blocker dosages when we can, it’s more important to achieve a target heart rate in these patients of 55-65 bpm.”
Dr. Cleland hypothesized, based on a report presented at the same meeting by a different research group, that reduced heart rate is not beneficial in HFrEF patients with atrial fibrillation because in this subgroup slower heart rates linked with an increased number of brief pauses in left ventricular pumping. These pauses may result in ventricular arrhythmias, he speculated. “It may be that beta-blockers are equally effective at slowing heart rate in patients with or without atrial fibrillation, but there is also harm from beta-blockers because they’re causing pauses in patients with atrial fibrillation,” he said.
These days, if he has a HFrEF patient with atrial fibrillation whose heart rate slows to 60 bpm, he will stop digoxin treatment if the patient is on that drug, and he will also reduce the beta-blocker dosage but not discontinue it.
The findings came from the Collaborative Systematic Overview of Randomized Controlled Trials of Beta-Blockers in the Treatment of Heart Failure (BB-META-HF), which included data from 11 large beta-blocker randomized trials in heart failure that had been published during 1993-2005. The analysis included data from 17,378 HFrEF patients, with 14,313 (82%) in sinus rhythm and 3,065 (18%) with atrial fibrillation. Follow-up data of patients on treatment was available for 15,007 of these patients.
Dr. Cleland and his associates showed in multivariate analyses that, when they controlled for several baseline demographic and clinical variables among patients in sinus rhythm who received a beta-blocker, the follow-up all-cause mortality fell by 36%, compared with placebo, in patients with a resting baseline heart rate of less than 70 bpm; by 21%, compared with placebo, in patients with a baseline heart rate of 70-90 bpm; and by 38%, compared with placebo, in patients with a baseline heart rate of more than 90 bpm. All three reductions were statistically significant. In contrast, among patients who also had atrial fibrillation beta-blocker treatment linked with no significant mortality reduction, compared with placebo, for patients with any baseline heart rate. Concurrently with Dr. Cleland’s report at the meeting the results appeared online (J Amer Coll Cardiol. 2017 Apr 30. doi: 10.1016/j.jacc.2017.04.001).
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
AT HEART FAILURE 2017
Key clinical point:
Major finding: All-cause mortality was similar in patients with HFrEF and atrial fibrillation regardless of whether they received a beta-blocker or placebo.
Data source: BB-META-HF, a meta-analysis of 11 beta-blocker treatment trials with 17,378 HFrEF patients.
Disclosures: BB-META-HF received funding from Menarini and GlaxoSmithKline. Dr. Cleland has received research funding and honoraria from GlaxoSmithKline.
FDA approves Sapien 3 transcatheter valve for bioprosthetic valve failure
The Food and Drug Administration announced June 5 the approval of an expanded indication for the Sapien 3 Transcatheter Heart Valve (THV) for patients with symptomatic heart disease caused by failure of a previously placed bioprosthetic aortic or mitral valve who have a risk of death or severe complications from repeat surgery.
This is the first FDA approval for the expanded use of the Sapien 3 THV as a valve-in-valve treatment. Such procedures provide an alternative to repeat surgery.
“For the first time, a regulatory agency is approving a transcatheter heart valve as a valve-in-valve treatment when bioprosthetic mitral or aortic valves fail in patients who are at high or greater risk of complications from repeat surgery,” Bram Zuckerman, MD, director of the division of cardiovascular devices at the FDA’s Center for Devices and Radiological Health, said in a press release. “This new approval offers U.S. patients with failing surgical bioprosthetic aortic or mitral valves a less-invasive treatment option.”
Originally, the FDA approved the Sapien 3 THV for transcatheter aortic valve replacement (TAVR) as an alternative to surgical aortic valve replacement for patients with native aortic stenosis whose risk for death or severe complications from surgery is high or greater. Then in 2016, the FDA expanded the TAVR indication for Sapien 3 THV to include patients who are at intermediate surgical risk for death or complications.
Read the full press release on the FDA’s website.
The Food and Drug Administration announced June 5 the approval of an expanded indication for the Sapien 3 Transcatheter Heart Valve (THV) for patients with symptomatic heart disease caused by failure of a previously placed bioprosthetic aortic or mitral valve who have a risk of death or severe complications from repeat surgery.
This is the first FDA approval for the expanded use of the Sapien 3 THV as a valve-in-valve treatment. Such procedures provide an alternative to repeat surgery.
“For the first time, a regulatory agency is approving a transcatheter heart valve as a valve-in-valve treatment when bioprosthetic mitral or aortic valves fail in patients who are at high or greater risk of complications from repeat surgery,” Bram Zuckerman, MD, director of the division of cardiovascular devices at the FDA’s Center for Devices and Radiological Health, said in a press release. “This new approval offers U.S. patients with failing surgical bioprosthetic aortic or mitral valves a less-invasive treatment option.”
Originally, the FDA approved the Sapien 3 THV for transcatheter aortic valve replacement (TAVR) as an alternative to surgical aortic valve replacement for patients with native aortic stenosis whose risk for death or severe complications from surgery is high or greater. Then in 2016, the FDA expanded the TAVR indication for Sapien 3 THV to include patients who are at intermediate surgical risk for death or complications.
Read the full press release on the FDA’s website.
The Food and Drug Administration announced June 5 the approval of an expanded indication for the Sapien 3 Transcatheter Heart Valve (THV) for patients with symptomatic heart disease caused by failure of a previously placed bioprosthetic aortic or mitral valve who have a risk of death or severe complications from repeat surgery.
This is the first FDA approval for the expanded use of the Sapien 3 THV as a valve-in-valve treatment. Such procedures provide an alternative to repeat surgery.
“For the first time, a regulatory agency is approving a transcatheter heart valve as a valve-in-valve treatment when bioprosthetic mitral or aortic valves fail in patients who are at high or greater risk of complications from repeat surgery,” Bram Zuckerman, MD, director of the division of cardiovascular devices at the FDA’s Center for Devices and Radiological Health, said in a press release. “This new approval offers U.S. patients with failing surgical bioprosthetic aortic or mitral valves a less-invasive treatment option.”
Originally, the FDA approved the Sapien 3 THV for transcatheter aortic valve replacement (TAVR) as an alternative to surgical aortic valve replacement for patients with native aortic stenosis whose risk for death or severe complications from surgery is high or greater. Then in 2016, the FDA expanded the TAVR indication for Sapien 3 THV to include patients who are at intermediate surgical risk for death or complications.
Read the full press release on the FDA’s website.
A prescription for heart failure success: Change the name
PARIS – Does heart failure’s name doom any progress against the disease?
That was the provocative premise advanced by Lynne Warner Stevenson, MD, who suggested that efforts to prevent, diagnose, and treat the disease would go better if it could only jettison that unfortunate word “failure,” its hard-wired albatross.
Dr. Stevenson offered several potentially superior alternatives, including cardiac insufficiency, heart dysfunction, and her favorite, cardiomyopathy.
“Is heart failure still the best diagnosis” for the entire spectrum of disease that most patients progress through ,including the many patients in earlier stages of the disease who do not have a truly failing heart? “Perhaps cardiomyopathy is the condition and heart failure is the transition,” she proposed.
To Dr. Stevenson, it’s more than just semantics.
“Words are hugely powerful,” she explained in an interview following her talk. “I think patients do not want to be seen as having heart failure. They don’t want to think of themselves as having heart failure. I think it can make them delay getting care, and it makes them ignore the disease. I worry about that a lot. I also worry that patients don’t provide support to each other that they could. Patients tend to hide that they have heart failure. We need to come up with a term that does not make patients ashamed of their disease.”
Part of the problem, Dr. Stevenson said, is that the name heart failure can be very misleading depending on the stage of the disease that patients have. Patients with stage B (presymptomatic) disease and those with mild stage C disease “don’t see themselves as having heart failure,” as having a heart that has failed them. “We need to be able to convince these patients that they have a disease that we need to treat carefully and aggressively.”
Additionally, labeling tens of millions of people as having stage A heart failure, which is presymptomatic and occurs before the heart shows any sign of damage or dysfunction, is also counterproductive, maintained Dr. Stevenson, professor of medicine at Harvard Medical School and director of the Cardiomyopathy and Heart Failure Program at Brigham and Women’s Hospital in Boston.
“So many people are at risk of developing heart failure,” she noted, including patients with hypertension, diabetes, or coronary artery disease. To label them all as already also having heart failure at that stage “tends to make them ignore the disease that we are trying to get them to pay attention to. Telling patients they have the disease that we are trying to prevent doesn’t help.”
Calling the whole range of the disease heart failure also confuses patients and others. “Patients ask me, ‘How can I have heart failure without any symptoms?’ ‘My ejection fraction improved to almost normal; do I still have heart failure?’ and ‘I don’t understand how my heart muscle is strong but my heart is failing,’ ” she said
For Dr. Stevenson, perhaps the biggest problem is the stigma of failure and the way that word ties a huge weight to the disease that prompts patients and caregivers alike to relegate it to a hidden and neglected place.
“It’s failure. Who is proud to have heart failure? Where are the marches for heart failure? Where are the celebrity champions for heart failure? We have celebrities who are happy to admit that they have Parkinson’s disease, ALS [amyotrophic lateral sclerosis], drug addiction, and even erectile dysfunction, but no one wants to say they have heart failure. We can’t get any traction behind heart failure. It doesn’t sound very inspiring,” an issue that even percolates down to dissuading clinicians from pursuing a career in heart failure care. Young people do not aspire to go into failure, she said.
“We need to call it something else.”
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
PARIS – Does heart failure’s name doom any progress against the disease?
That was the provocative premise advanced by Lynne Warner Stevenson, MD, who suggested that efforts to prevent, diagnose, and treat the disease would go better if it could only jettison that unfortunate word “failure,” its hard-wired albatross.
Dr. Stevenson offered several potentially superior alternatives, including cardiac insufficiency, heart dysfunction, and her favorite, cardiomyopathy.
“Is heart failure still the best diagnosis” for the entire spectrum of disease that most patients progress through ,including the many patients in earlier stages of the disease who do not have a truly failing heart? “Perhaps cardiomyopathy is the condition and heart failure is the transition,” she proposed.
To Dr. Stevenson, it’s more than just semantics.
“Words are hugely powerful,” she explained in an interview following her talk. “I think patients do not want to be seen as having heart failure. They don’t want to think of themselves as having heart failure. I think it can make them delay getting care, and it makes them ignore the disease. I worry about that a lot. I also worry that patients don’t provide support to each other that they could. Patients tend to hide that they have heart failure. We need to come up with a term that does not make patients ashamed of their disease.”
Part of the problem, Dr. Stevenson said, is that the name heart failure can be very misleading depending on the stage of the disease that patients have. Patients with stage B (presymptomatic) disease and those with mild stage C disease “don’t see themselves as having heart failure,” as having a heart that has failed them. “We need to be able to convince these patients that they have a disease that we need to treat carefully and aggressively.”
Additionally, labeling tens of millions of people as having stage A heart failure, which is presymptomatic and occurs before the heart shows any sign of damage or dysfunction, is also counterproductive, maintained Dr. Stevenson, professor of medicine at Harvard Medical School and director of the Cardiomyopathy and Heart Failure Program at Brigham and Women’s Hospital in Boston.
“So many people are at risk of developing heart failure,” she noted, including patients with hypertension, diabetes, or coronary artery disease. To label them all as already also having heart failure at that stage “tends to make them ignore the disease that we are trying to get them to pay attention to. Telling patients they have the disease that we are trying to prevent doesn’t help.”
Calling the whole range of the disease heart failure also confuses patients and others. “Patients ask me, ‘How can I have heart failure without any symptoms?’ ‘My ejection fraction improved to almost normal; do I still have heart failure?’ and ‘I don’t understand how my heart muscle is strong but my heart is failing,’ ” she said
For Dr. Stevenson, perhaps the biggest problem is the stigma of failure and the way that word ties a huge weight to the disease that prompts patients and caregivers alike to relegate it to a hidden and neglected place.
“It’s failure. Who is proud to have heart failure? Where are the marches for heart failure? Where are the celebrity champions for heart failure? We have celebrities who are happy to admit that they have Parkinson’s disease, ALS [amyotrophic lateral sclerosis], drug addiction, and even erectile dysfunction, but no one wants to say they have heart failure. We can’t get any traction behind heart failure. It doesn’t sound very inspiring,” an issue that even percolates down to dissuading clinicians from pursuing a career in heart failure care. Young people do not aspire to go into failure, she said.
“We need to call it something else.”
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
PARIS – Does heart failure’s name doom any progress against the disease?
That was the provocative premise advanced by Lynne Warner Stevenson, MD, who suggested that efforts to prevent, diagnose, and treat the disease would go better if it could only jettison that unfortunate word “failure,” its hard-wired albatross.
Dr. Stevenson offered several potentially superior alternatives, including cardiac insufficiency, heart dysfunction, and her favorite, cardiomyopathy.
“Is heart failure still the best diagnosis” for the entire spectrum of disease that most patients progress through ,including the many patients in earlier stages of the disease who do not have a truly failing heart? “Perhaps cardiomyopathy is the condition and heart failure is the transition,” she proposed.
To Dr. Stevenson, it’s more than just semantics.
“Words are hugely powerful,” she explained in an interview following her talk. “I think patients do not want to be seen as having heart failure. They don’t want to think of themselves as having heart failure. I think it can make them delay getting care, and it makes them ignore the disease. I worry about that a lot. I also worry that patients don’t provide support to each other that they could. Patients tend to hide that they have heart failure. We need to come up with a term that does not make patients ashamed of their disease.”
Part of the problem, Dr. Stevenson said, is that the name heart failure can be very misleading depending on the stage of the disease that patients have. Patients with stage B (presymptomatic) disease and those with mild stage C disease “don’t see themselves as having heart failure,” as having a heart that has failed them. “We need to be able to convince these patients that they have a disease that we need to treat carefully and aggressively.”
Additionally, labeling tens of millions of people as having stage A heart failure, which is presymptomatic and occurs before the heart shows any sign of damage or dysfunction, is also counterproductive, maintained Dr. Stevenson, professor of medicine at Harvard Medical School and director of the Cardiomyopathy and Heart Failure Program at Brigham and Women’s Hospital in Boston.
“So many people are at risk of developing heart failure,” she noted, including patients with hypertension, diabetes, or coronary artery disease. To label them all as already also having heart failure at that stage “tends to make them ignore the disease that we are trying to get them to pay attention to. Telling patients they have the disease that we are trying to prevent doesn’t help.”
Calling the whole range of the disease heart failure also confuses patients and others. “Patients ask me, ‘How can I have heart failure without any symptoms?’ ‘My ejection fraction improved to almost normal; do I still have heart failure?’ and ‘I don’t understand how my heart muscle is strong but my heart is failing,’ ” she said
For Dr. Stevenson, perhaps the biggest problem is the stigma of failure and the way that word ties a huge weight to the disease that prompts patients and caregivers alike to relegate it to a hidden and neglected place.
“It’s failure. Who is proud to have heart failure? Where are the marches for heart failure? Where are the celebrity champions for heart failure? We have celebrities who are happy to admit that they have Parkinson’s disease, ALS [amyotrophic lateral sclerosis], drug addiction, and even erectile dysfunction, but no one wants to say they have heart failure. We can’t get any traction behind heart failure. It doesn’t sound very inspiring,” an issue that even percolates down to dissuading clinicians from pursuing a career in heart failure care. Young people do not aspire to go into failure, she said.
“We need to call it something else.”
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
EXPERT ANALYSIS FROM HEART FAILURE 2017
Spironolactone’s HFpEF benefit happens mostly in women
PARIS – Just when the aldosterone receptor antagonists spironolactone and eplerenone received official recognition in the 2017 U.S. heart failure guidelines as the only drug class that benefits patients with heart failure with preserved ejection fraction (HFpEF), a new post-hoc analysis of the pivotal evidence suggests the benefit is mostly in women, with little benefit to men.
The new analysis used data collected from TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist), which randomized patients with HFpEF to treatment with spironolactone or placebo. Results from the overall study were neutral for the primary outcome of cardiovascular death, aborted cardiac arrest, and heart failure hospitalization (N Engl J Med. 2014 April 10;370[15]:1383-92). However, a series of post-hoc analyses showed that a high percentage of patients enrolled at centers in Russia or Georgia did not match the expected HFpEF profile, and these patients had poor responses to spironolactone. In contrast, patients enrolled at centers in the Americas more frequently matched the study’s target HFpEF profile, and they showed significant improvement for the primary endpoint (Circulation. 2015 Jan 6;131[1]:34-42).
“The observation that most of the benefit [from spironolactone treatment] may have been in women is interesting, but I don’t think that it would stop me from using [an aldosterone receptor antagonist] in men,” said Dr. Kao while presenting his report. The outcomes in both men and women “head in the same direction. It’s just that the mortality benefit is much clearer in women,” said Dr. Kao, a cardiologist at the University of Colorado at Denver, Aurora.
Among the patients enrolled at centers in North and South America, 882 were women, and 885 were men. Dr. Kao used the data collected in TOPCAT to calculate the impact of spironolactone treatment relative to placebo on outcomes just among women in the Americas and just among men.
The difference in all-cause mortality associated with spironolactone treatment had an even sharper sex disparity that in the primary outcome. Overall, all-cause mortality was 28% less common among women, compared with men, in the Americas. Among women, spironolactone treatment linked with a 30% reduced all-cause mortality rate, compared with placebo. Among men, the survival curves of those on spironolactone or placebo superimposed.
Dr. Kao said that published study results in rats had suggested that eplerenone (Inspra), an aldosterone receptor antagonist like spironolactone, had a more potent effect in females rats, compared with male rats, for preserving left ventricular function and size following myocardial damage. In addition, women with HFpEF often have more left ventricular hypertrophy, while men often have more diastolic dysfunction, and prior findings had suggested that aldosterone plays a role in left ventricular hypertrophy.
TOPCAT received no commercial funding. Dr. Kao had no disclosures.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
PARIS – Just when the aldosterone receptor antagonists spironolactone and eplerenone received official recognition in the 2017 U.S. heart failure guidelines as the only drug class that benefits patients with heart failure with preserved ejection fraction (HFpEF), a new post-hoc analysis of the pivotal evidence suggests the benefit is mostly in women, with little benefit to men.
The new analysis used data collected from TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist), which randomized patients with HFpEF to treatment with spironolactone or placebo. Results from the overall study were neutral for the primary outcome of cardiovascular death, aborted cardiac arrest, and heart failure hospitalization (N Engl J Med. 2014 April 10;370[15]:1383-92). However, a series of post-hoc analyses showed that a high percentage of patients enrolled at centers in Russia or Georgia did not match the expected HFpEF profile, and these patients had poor responses to spironolactone. In contrast, patients enrolled at centers in the Americas more frequently matched the study’s target HFpEF profile, and they showed significant improvement for the primary endpoint (Circulation. 2015 Jan 6;131[1]:34-42).
“The observation that most of the benefit [from spironolactone treatment] may have been in women is interesting, but I don’t think that it would stop me from using [an aldosterone receptor antagonist] in men,” said Dr. Kao while presenting his report. The outcomes in both men and women “head in the same direction. It’s just that the mortality benefit is much clearer in women,” said Dr. Kao, a cardiologist at the University of Colorado at Denver, Aurora.
Among the patients enrolled at centers in North and South America, 882 were women, and 885 were men. Dr. Kao used the data collected in TOPCAT to calculate the impact of spironolactone treatment relative to placebo on outcomes just among women in the Americas and just among men.
The difference in all-cause mortality associated with spironolactone treatment had an even sharper sex disparity that in the primary outcome. Overall, all-cause mortality was 28% less common among women, compared with men, in the Americas. Among women, spironolactone treatment linked with a 30% reduced all-cause mortality rate, compared with placebo. Among men, the survival curves of those on spironolactone or placebo superimposed.
Dr. Kao said that published study results in rats had suggested that eplerenone (Inspra), an aldosterone receptor antagonist like spironolactone, had a more potent effect in females rats, compared with male rats, for preserving left ventricular function and size following myocardial damage. In addition, women with HFpEF often have more left ventricular hypertrophy, while men often have more diastolic dysfunction, and prior findings had suggested that aldosterone plays a role in left ventricular hypertrophy.
TOPCAT received no commercial funding. Dr. Kao had no disclosures.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
PARIS – Just when the aldosterone receptor antagonists spironolactone and eplerenone received official recognition in the 2017 U.S. heart failure guidelines as the only drug class that benefits patients with heart failure with preserved ejection fraction (HFpEF), a new post-hoc analysis of the pivotal evidence suggests the benefit is mostly in women, with little benefit to men.
The new analysis used data collected from TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist), which randomized patients with HFpEF to treatment with spironolactone or placebo. Results from the overall study were neutral for the primary outcome of cardiovascular death, aborted cardiac arrest, and heart failure hospitalization (N Engl J Med. 2014 April 10;370[15]:1383-92). However, a series of post-hoc analyses showed that a high percentage of patients enrolled at centers in Russia or Georgia did not match the expected HFpEF profile, and these patients had poor responses to spironolactone. In contrast, patients enrolled at centers in the Americas more frequently matched the study’s target HFpEF profile, and they showed significant improvement for the primary endpoint (Circulation. 2015 Jan 6;131[1]:34-42).
“The observation that most of the benefit [from spironolactone treatment] may have been in women is interesting, but I don’t think that it would stop me from using [an aldosterone receptor antagonist] in men,” said Dr. Kao while presenting his report. The outcomes in both men and women “head in the same direction. It’s just that the mortality benefit is much clearer in women,” said Dr. Kao, a cardiologist at the University of Colorado at Denver, Aurora.
Among the patients enrolled at centers in North and South America, 882 were women, and 885 were men. Dr. Kao used the data collected in TOPCAT to calculate the impact of spironolactone treatment relative to placebo on outcomes just among women in the Americas and just among men.
The difference in all-cause mortality associated with spironolactone treatment had an even sharper sex disparity that in the primary outcome. Overall, all-cause mortality was 28% less common among women, compared with men, in the Americas. Among women, spironolactone treatment linked with a 30% reduced all-cause mortality rate, compared with placebo. Among men, the survival curves of those on spironolactone or placebo superimposed.
Dr. Kao said that published study results in rats had suggested that eplerenone (Inspra), an aldosterone receptor antagonist like spironolactone, had a more potent effect in females rats, compared with male rats, for preserving left ventricular function and size following myocardial damage. In addition, women with HFpEF often have more left ventricular hypertrophy, while men often have more diastolic dysfunction, and prior findings had suggested that aldosterone plays a role in left ventricular hypertrophy.
TOPCAT received no commercial funding. Dr. Kao had no disclosures.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
AT HEART FAILURE 2017
Key clinical point:
Major finding: Women from the Americas in TOPCAT had an 18% lower rate of primary endpoint events, compared with men in the trial.
Data source: TOPCAT, a multicenter, randomized study with 3,445 patients.
Disclosures: TOPCAT received no commercial funding. Dr. Kao had no disclosures.
New heart failure guidelines prioritize prevention
The latest update to U.S. guidelines for heart failure management, released at the end of April , puts unprecedented emphasis on heart failure prevention and also shines a brighter light on patients at risk for developing heart failure – people with hypertension, diabetes, or coronary artery disease.
“We have embraced the fact that heart failure can be prevented and that the progression of heart failure can be interrupted, and we articulated how we can use biomarkers to screen patients with asymptomatic left ventricular dysfunction,” said Clyde W. Yancy, MD, chair of the writing group that issued the 2017 focused update to the heart failure management guidelines on behalf of the American College of Cardiology, the American Heart Association, and the Heart Failure Society of America. (Circulation. 2017 Apr 28. doi: 10.1161/CIR.0000000000000509).
This means that, for the first time, these guidelines focus on stage A heart failure patients, those without symptoms or detectable left ventricular dysfunction but at risk for heart failure, a heart failure subgroup that was ignored in the past. Prevention is most immediate for stage A patients. The new guidelines cite the stage A definition from the 2009 guidelines: patients with “risk factors that clearly predispose toward the development of heart failure. For example, patients with coronary artery disease, hypertension, or diabetes mellitus who do not yet demonstrate impaired left ventricular function.”
The number of patients with coronary artery disease, hypertension, or diabetes is pretty large. The new heart failure guidelines apply to many people.
“The mindset [on heart failure] has been on treatment, not prevention. There is far more focus [in the new guidelines] on prevention than ever before,” commented Javed Butler, MD, professor and chief of cardiology at Stony Brook (N.Y.) University and a member of the guideline writing panel.
“One reason why heart failure prevention has not been a focus was because people thought that, if you prevented coronary artery disease, you prevented heart failure. What we’ve learned is that a lot of heart failure is not ischemic and not from overt coronary disease, especially age-related HFpEF [heart failure with preserved ejection fraction]. Hopefully, these guidelines will spur more interest in prevention and risk factor control,” Dr. Butler said in an interview.
It starts with blood pressure
The guidelines contain an entirely new section devoted to blood pressure, and, while part of the section deals with a target blood pressure for symptomatic (stage C) heart failure patients (a goal systolic pressure of less than 130 mm Hg for patients with either a preserved or reduced ejection fraction), the first entry is a target blood pressure of less than 130/80 mm Hg for all stage A heart failure patients.
Because stage A is defined to include any adult with hypertension, the new heart failure guidelines set a new blood pressure treatment goal for all U.S. adults with hypertension at a time when the long-awaited revision to U.S. hypertension management guidelines from the ACC and AHA are still pending. Until the new hypertension guidelines come out – they’re expected later this year – the blood pressure target set in the heart failure guidelines will have to suffice.
Indeed, the less than 130/80-mm Hg target for on-treatment blood pressure set for heart failure prevention in the new guidelines was picked to “harmonize” with the guidelines that the ACC and AHA hypertension panel will soon release, Dr. Jessup said in an interview.
The main evidence for this target, lower than in most prior U.S. hypertension guidelines, comes from SPRINT (Systolic Blood Pressure Intervention Trial) (N Engl J Med. 2015 Nov 26;373[22]:2103-16). In that trial, the goal blood pressure that linked with the best outcomes was less than 120/80 mm Hg, although the average achieved systolic blood pressure was above that goal with a mean systolic pressure of 121.5 mm Hg. One reason for setting a higher goal systolic pressure for practice was that analyses have shown that blood pressure measurement in SPRINT did not perform like conventional measurements in routine practice. SPRINT patients appeared to have lower measured pressures than they would have recorded had they been measured by more conventional means (Hypertension. 2017 January;69[1]:15-9).
“The way that blood pressures were measured in SPRINT, a pressure of 120/80 mm Hg in the trial was akin to a pressure of 130/80 mm Hg in an office,” Dr. Yancy, chief of cardiology at Northwestern University, Chicago, said in an interview. “To avoid dangerous hypotension and to approximate SPRINT, an office pressure of less than 130 mm Hg is a reasonable number.”
New role for BNP screening
Stage A patients are more than just the target for more aggressive hypertension control. They are now also potential candidates for screening for an elevated blood level of brain natriuretic peptide (BNP) or N-terminal (NT)–proBNP. The guidelines panel makes this a level IIa recommendation, saying that a screening BNP test in patients at risk for developing heart failure can be useful if followed by team-based care and optimized guideline directed medical therapy.
This guideline follows the lead of two successful controlled trials that focused more aggressive preventive treatments on stage A patients with an elevated level of BNP or NT-proBNP – the STOP-HF (JAMA. 2013 July 3;310[1]:66-74) and PONTIAC (J Am Coll Cardiol. 2013 Oct;62[15]:1365-72) trials. The target population for some type of BNP screening are patients with cardiovascular disease, vascular disease, diabetes, obesity, or hypertension, Dr. Yancy said. “It was evident in STOP-HF that, if you screened and intervened, you could make a difference” in the development of heart failure.
The STOP-HF intervention included “optimal risk factor management” and “coaching by a specialist nurse who emphasized individual risk status and the importance of adherence to medication and healthy lifestyle behaviors.”
The guidelines aren’t clear on which patients at risk for developing heart failure, stage A patients, should get screened with BNP or NT-proBNP. Dr. Jessup said that it’s for patients in whom a positive result would trigger more aggressive management.
Getting a BNP on a suspect patient can raise a red flag to the patient, as well as to the physician, that more intervention is needed. “It’s easy for a physician to ignore a high-risk patient who looks okay and feels okay.” A BNP or NT-proBNP test can pick out the patients who shouldn’t be ignored, Dr. Januzzi said.
HFpEF treatment now possible
Another groundbreaking change in the guidelines is inclusion, for the first time, of a medical treatment specific for HFpEF. The aldosterone receptor antagonists (ARAs) spironolactone and eplerenone received a class IIb recommendation: An ARA might be considered to decrease hospitalizations in patients with HFpEF with an ejection fraction of at least 45%, an elevated BNP or recent hospitalization, and good renal function and potassium level.
The “might be considered” recommendation is guarded but understandable given that the evidence comes from the somewhat controversial, post-hoc analysis of data from the pivotal TOPCAT trial (N Engl J Med. 2014 Apr 10;370[15]:1383-92) that focused on just the roughly half of patients seen at centers in North or South America (Circulation. 2015 Jan 6;131[1]:34-42).
“It would be irresponsible to overlook the potential that [ARAs] may help patients who looks like the ones enrolled in TOPCAT in the Americas,” said Dr. Yancy. “We blended evidence and pragmatism and said that the field needs this” treatment. He said that an ARA was a reasonable option for HFpEF patients with symptoms of heart failure and a positive biomarker test result.
Dr. Butler largely agreed. ARA treatment is for HFpEF patients with symptomatic heart failure and either a history of hospitalization or a high BNP level, he said.
“I was surprised by how strongly the committee felt there was a reasonable signal of help from ARAs in HFpEF,” said Dr. Jessup. “I believe in them too,” she added.
Dr. Jessup suggested targeting an ARA to a HFpEF patient with some hypertension, some volume problem, some peripheral edema, and a lot of breathlessness but with no underlying ischemia. “I use an ARA on these patients pretty quickly,” Dr. Jessup said. It’s best to start with a low dosage and see how the patient responds. “The best responders have a really stiff heart” and are usually not the more elderly HFpEF patients. ARA treatment also provides more steady volume control, superior to furosemide, she said.
Yet more additions
The revised guidelines contain even more changes. “We say that checking for anemia is important and how iron is an intervention that might make a difference,” said Dr. Jessup. Also, primary care physicians and cardiologists “should look for obstructive sleep apnea” in heart failure patients for whom “intervention with weight loss might help,” she said.
Another feature is the focus on tailored treatment, with many treatment elements that need customizing to each different type of heart failure patient. “Not every drug needs to be given to every patient,” Dr. Yancy warned.
The specifics of how to orchestrate all the guidelines into a coherent management plan may become clearer later this year, when the ACC/AHA group will release a follow-up “Heart Failure Pathways” document, aimed at bridging the gap between guidelines and actual clinical practice, Dr. Yancy said. “We want more value from writing the guidelines. The biggest obstacle is how to implement them,” and that’s what the pathways follow-up will address.
“The biggest challenge the societies have is how to motivate physicians and nurses to more aggressively treat heart failure,” said Dr. Butler.
Dr. Yancy and Dr. Jessup had no disclosures. Dr. Butler has been a consultant to 11 companies. Dr. Januzzi has been a consultant to Critical Diagnostics, Novartis, Phillips, Roche Diagnostics, and Sphingotec, and he has received research support from Amgen, Boehringer Ingelheim, Janssen, and Prevencio.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
The latest update to U.S. guidelines for heart failure management, released at the end of April , puts unprecedented emphasis on heart failure prevention and also shines a brighter light on patients at risk for developing heart failure – people with hypertension, diabetes, or coronary artery disease.
“We have embraced the fact that heart failure can be prevented and that the progression of heart failure can be interrupted, and we articulated how we can use biomarkers to screen patients with asymptomatic left ventricular dysfunction,” said Clyde W. Yancy, MD, chair of the writing group that issued the 2017 focused update to the heart failure management guidelines on behalf of the American College of Cardiology, the American Heart Association, and the Heart Failure Society of America. (Circulation. 2017 Apr 28. doi: 10.1161/CIR.0000000000000509).
This means that, for the first time, these guidelines focus on stage A heart failure patients, those without symptoms or detectable left ventricular dysfunction but at risk for heart failure, a heart failure subgroup that was ignored in the past. Prevention is most immediate for stage A patients. The new guidelines cite the stage A definition from the 2009 guidelines: patients with “risk factors that clearly predispose toward the development of heart failure. For example, patients with coronary artery disease, hypertension, or diabetes mellitus who do not yet demonstrate impaired left ventricular function.”
The number of patients with coronary artery disease, hypertension, or diabetes is pretty large. The new heart failure guidelines apply to many people.
“The mindset [on heart failure] has been on treatment, not prevention. There is far more focus [in the new guidelines] on prevention than ever before,” commented Javed Butler, MD, professor and chief of cardiology at Stony Brook (N.Y.) University and a member of the guideline writing panel.
“One reason why heart failure prevention has not been a focus was because people thought that, if you prevented coronary artery disease, you prevented heart failure. What we’ve learned is that a lot of heart failure is not ischemic and not from overt coronary disease, especially age-related HFpEF [heart failure with preserved ejection fraction]. Hopefully, these guidelines will spur more interest in prevention and risk factor control,” Dr. Butler said in an interview.
It starts with blood pressure
The guidelines contain an entirely new section devoted to blood pressure, and, while part of the section deals with a target blood pressure for symptomatic (stage C) heart failure patients (a goal systolic pressure of less than 130 mm Hg for patients with either a preserved or reduced ejection fraction), the first entry is a target blood pressure of less than 130/80 mm Hg for all stage A heart failure patients.
Because stage A is defined to include any adult with hypertension, the new heart failure guidelines set a new blood pressure treatment goal for all U.S. adults with hypertension at a time when the long-awaited revision to U.S. hypertension management guidelines from the ACC and AHA are still pending. Until the new hypertension guidelines come out – they’re expected later this year – the blood pressure target set in the heart failure guidelines will have to suffice.
Indeed, the less than 130/80-mm Hg target for on-treatment blood pressure set for heart failure prevention in the new guidelines was picked to “harmonize” with the guidelines that the ACC and AHA hypertension panel will soon release, Dr. Jessup said in an interview.
The main evidence for this target, lower than in most prior U.S. hypertension guidelines, comes from SPRINT (Systolic Blood Pressure Intervention Trial) (N Engl J Med. 2015 Nov 26;373[22]:2103-16). In that trial, the goal blood pressure that linked with the best outcomes was less than 120/80 mm Hg, although the average achieved systolic blood pressure was above that goal with a mean systolic pressure of 121.5 mm Hg. One reason for setting a higher goal systolic pressure for practice was that analyses have shown that blood pressure measurement in SPRINT did not perform like conventional measurements in routine practice. SPRINT patients appeared to have lower measured pressures than they would have recorded had they been measured by more conventional means (Hypertension. 2017 January;69[1]:15-9).
“The way that blood pressures were measured in SPRINT, a pressure of 120/80 mm Hg in the trial was akin to a pressure of 130/80 mm Hg in an office,” Dr. Yancy, chief of cardiology at Northwestern University, Chicago, said in an interview. “To avoid dangerous hypotension and to approximate SPRINT, an office pressure of less than 130 mm Hg is a reasonable number.”
New role for BNP screening
Stage A patients are more than just the target for more aggressive hypertension control. They are now also potential candidates for screening for an elevated blood level of brain natriuretic peptide (BNP) or N-terminal (NT)–proBNP. The guidelines panel makes this a level IIa recommendation, saying that a screening BNP test in patients at risk for developing heart failure can be useful if followed by team-based care and optimized guideline directed medical therapy.
This guideline follows the lead of two successful controlled trials that focused more aggressive preventive treatments on stage A patients with an elevated level of BNP or NT-proBNP – the STOP-HF (JAMA. 2013 July 3;310[1]:66-74) and PONTIAC (J Am Coll Cardiol. 2013 Oct;62[15]:1365-72) trials. The target population for some type of BNP screening are patients with cardiovascular disease, vascular disease, diabetes, obesity, or hypertension, Dr. Yancy said. “It was evident in STOP-HF that, if you screened and intervened, you could make a difference” in the development of heart failure.
The STOP-HF intervention included “optimal risk factor management” and “coaching by a specialist nurse who emphasized individual risk status and the importance of adherence to medication and healthy lifestyle behaviors.”
The guidelines aren’t clear on which patients at risk for developing heart failure, stage A patients, should get screened with BNP or NT-proBNP. Dr. Jessup said that it’s for patients in whom a positive result would trigger more aggressive management.
Getting a BNP on a suspect patient can raise a red flag to the patient, as well as to the physician, that more intervention is needed. “It’s easy for a physician to ignore a high-risk patient who looks okay and feels okay.” A BNP or NT-proBNP test can pick out the patients who shouldn’t be ignored, Dr. Januzzi said.
HFpEF treatment now possible
Another groundbreaking change in the guidelines is inclusion, for the first time, of a medical treatment specific for HFpEF. The aldosterone receptor antagonists (ARAs) spironolactone and eplerenone received a class IIb recommendation: An ARA might be considered to decrease hospitalizations in patients with HFpEF with an ejection fraction of at least 45%, an elevated BNP or recent hospitalization, and good renal function and potassium level.
The “might be considered” recommendation is guarded but understandable given that the evidence comes from the somewhat controversial, post-hoc analysis of data from the pivotal TOPCAT trial (N Engl J Med. 2014 Apr 10;370[15]:1383-92) that focused on just the roughly half of patients seen at centers in North or South America (Circulation. 2015 Jan 6;131[1]:34-42).
“It would be irresponsible to overlook the potential that [ARAs] may help patients who looks like the ones enrolled in TOPCAT in the Americas,” said Dr. Yancy. “We blended evidence and pragmatism and said that the field needs this” treatment. He said that an ARA was a reasonable option for HFpEF patients with symptoms of heart failure and a positive biomarker test result.
Dr. Butler largely agreed. ARA treatment is for HFpEF patients with symptomatic heart failure and either a history of hospitalization or a high BNP level, he said.
“I was surprised by how strongly the committee felt there was a reasonable signal of help from ARAs in HFpEF,” said Dr. Jessup. “I believe in them too,” she added.
Dr. Jessup suggested targeting an ARA to a HFpEF patient with some hypertension, some volume problem, some peripheral edema, and a lot of breathlessness but with no underlying ischemia. “I use an ARA on these patients pretty quickly,” Dr. Jessup said. It’s best to start with a low dosage and see how the patient responds. “The best responders have a really stiff heart” and are usually not the more elderly HFpEF patients. ARA treatment also provides more steady volume control, superior to furosemide, she said.
Yet more additions
The revised guidelines contain even more changes. “We say that checking for anemia is important and how iron is an intervention that might make a difference,” said Dr. Jessup. Also, primary care physicians and cardiologists “should look for obstructive sleep apnea” in heart failure patients for whom “intervention with weight loss might help,” she said.
Another feature is the focus on tailored treatment, with many treatment elements that need customizing to each different type of heart failure patient. “Not every drug needs to be given to every patient,” Dr. Yancy warned.
The specifics of how to orchestrate all the guidelines into a coherent management plan may become clearer later this year, when the ACC/AHA group will release a follow-up “Heart Failure Pathways” document, aimed at bridging the gap between guidelines and actual clinical practice, Dr. Yancy said. “We want more value from writing the guidelines. The biggest obstacle is how to implement them,” and that’s what the pathways follow-up will address.
“The biggest challenge the societies have is how to motivate physicians and nurses to more aggressively treat heart failure,” said Dr. Butler.
Dr. Yancy and Dr. Jessup had no disclosures. Dr. Butler has been a consultant to 11 companies. Dr. Januzzi has been a consultant to Critical Diagnostics, Novartis, Phillips, Roche Diagnostics, and Sphingotec, and he has received research support from Amgen, Boehringer Ingelheim, Janssen, and Prevencio.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
The latest update to U.S. guidelines for heart failure management, released at the end of April , puts unprecedented emphasis on heart failure prevention and also shines a brighter light on patients at risk for developing heart failure – people with hypertension, diabetes, or coronary artery disease.
“We have embraced the fact that heart failure can be prevented and that the progression of heart failure can be interrupted, and we articulated how we can use biomarkers to screen patients with asymptomatic left ventricular dysfunction,” said Clyde W. Yancy, MD, chair of the writing group that issued the 2017 focused update to the heart failure management guidelines on behalf of the American College of Cardiology, the American Heart Association, and the Heart Failure Society of America. (Circulation. 2017 Apr 28. doi: 10.1161/CIR.0000000000000509).
This means that, for the first time, these guidelines focus on stage A heart failure patients, those without symptoms or detectable left ventricular dysfunction but at risk for heart failure, a heart failure subgroup that was ignored in the past. Prevention is most immediate for stage A patients. The new guidelines cite the stage A definition from the 2009 guidelines: patients with “risk factors that clearly predispose toward the development of heart failure. For example, patients with coronary artery disease, hypertension, or diabetes mellitus who do not yet demonstrate impaired left ventricular function.”
The number of patients with coronary artery disease, hypertension, or diabetes is pretty large. The new heart failure guidelines apply to many people.
“The mindset [on heart failure] has been on treatment, not prevention. There is far more focus [in the new guidelines] on prevention than ever before,” commented Javed Butler, MD, professor and chief of cardiology at Stony Brook (N.Y.) University and a member of the guideline writing panel.
“One reason why heart failure prevention has not been a focus was because people thought that, if you prevented coronary artery disease, you prevented heart failure. What we’ve learned is that a lot of heart failure is not ischemic and not from overt coronary disease, especially age-related HFpEF [heart failure with preserved ejection fraction]. Hopefully, these guidelines will spur more interest in prevention and risk factor control,” Dr. Butler said in an interview.
It starts with blood pressure
The guidelines contain an entirely new section devoted to blood pressure, and, while part of the section deals with a target blood pressure for symptomatic (stage C) heart failure patients (a goal systolic pressure of less than 130 mm Hg for patients with either a preserved or reduced ejection fraction), the first entry is a target blood pressure of less than 130/80 mm Hg for all stage A heart failure patients.
Because stage A is defined to include any adult with hypertension, the new heart failure guidelines set a new blood pressure treatment goal for all U.S. adults with hypertension at a time when the long-awaited revision to U.S. hypertension management guidelines from the ACC and AHA are still pending. Until the new hypertension guidelines come out – they’re expected later this year – the blood pressure target set in the heart failure guidelines will have to suffice.
Indeed, the less than 130/80-mm Hg target for on-treatment blood pressure set for heart failure prevention in the new guidelines was picked to “harmonize” with the guidelines that the ACC and AHA hypertension panel will soon release, Dr. Jessup said in an interview.
The main evidence for this target, lower than in most prior U.S. hypertension guidelines, comes from SPRINT (Systolic Blood Pressure Intervention Trial) (N Engl J Med. 2015 Nov 26;373[22]:2103-16). In that trial, the goal blood pressure that linked with the best outcomes was less than 120/80 mm Hg, although the average achieved systolic blood pressure was above that goal with a mean systolic pressure of 121.5 mm Hg. One reason for setting a higher goal systolic pressure for practice was that analyses have shown that blood pressure measurement in SPRINT did not perform like conventional measurements in routine practice. SPRINT patients appeared to have lower measured pressures than they would have recorded had they been measured by more conventional means (Hypertension. 2017 January;69[1]:15-9).
“The way that blood pressures were measured in SPRINT, a pressure of 120/80 mm Hg in the trial was akin to a pressure of 130/80 mm Hg in an office,” Dr. Yancy, chief of cardiology at Northwestern University, Chicago, said in an interview. “To avoid dangerous hypotension and to approximate SPRINT, an office pressure of less than 130 mm Hg is a reasonable number.”
New role for BNP screening
Stage A patients are more than just the target for more aggressive hypertension control. They are now also potential candidates for screening for an elevated blood level of brain natriuretic peptide (BNP) or N-terminal (NT)–proBNP. The guidelines panel makes this a level IIa recommendation, saying that a screening BNP test in patients at risk for developing heart failure can be useful if followed by team-based care and optimized guideline directed medical therapy.
This guideline follows the lead of two successful controlled trials that focused more aggressive preventive treatments on stage A patients with an elevated level of BNP or NT-proBNP – the STOP-HF (JAMA. 2013 July 3;310[1]:66-74) and PONTIAC (J Am Coll Cardiol. 2013 Oct;62[15]:1365-72) trials. The target population for some type of BNP screening are patients with cardiovascular disease, vascular disease, diabetes, obesity, or hypertension, Dr. Yancy said. “It was evident in STOP-HF that, if you screened and intervened, you could make a difference” in the development of heart failure.
The STOP-HF intervention included “optimal risk factor management” and “coaching by a specialist nurse who emphasized individual risk status and the importance of adherence to medication and healthy lifestyle behaviors.”
The guidelines aren’t clear on which patients at risk for developing heart failure, stage A patients, should get screened with BNP or NT-proBNP. Dr. Jessup said that it’s for patients in whom a positive result would trigger more aggressive management.
Getting a BNP on a suspect patient can raise a red flag to the patient, as well as to the physician, that more intervention is needed. “It’s easy for a physician to ignore a high-risk patient who looks okay and feels okay.” A BNP or NT-proBNP test can pick out the patients who shouldn’t be ignored, Dr. Januzzi said.
HFpEF treatment now possible
Another groundbreaking change in the guidelines is inclusion, for the first time, of a medical treatment specific for HFpEF. The aldosterone receptor antagonists (ARAs) spironolactone and eplerenone received a class IIb recommendation: An ARA might be considered to decrease hospitalizations in patients with HFpEF with an ejection fraction of at least 45%, an elevated BNP or recent hospitalization, and good renal function and potassium level.
The “might be considered” recommendation is guarded but understandable given that the evidence comes from the somewhat controversial, post-hoc analysis of data from the pivotal TOPCAT trial (N Engl J Med. 2014 Apr 10;370[15]:1383-92) that focused on just the roughly half of patients seen at centers in North or South America (Circulation. 2015 Jan 6;131[1]:34-42).
“It would be irresponsible to overlook the potential that [ARAs] may help patients who looks like the ones enrolled in TOPCAT in the Americas,” said Dr. Yancy. “We blended evidence and pragmatism and said that the field needs this” treatment. He said that an ARA was a reasonable option for HFpEF patients with symptoms of heart failure and a positive biomarker test result.
Dr. Butler largely agreed. ARA treatment is for HFpEF patients with symptomatic heart failure and either a history of hospitalization or a high BNP level, he said.
“I was surprised by how strongly the committee felt there was a reasonable signal of help from ARAs in HFpEF,” said Dr. Jessup. “I believe in them too,” she added.
Dr. Jessup suggested targeting an ARA to a HFpEF patient with some hypertension, some volume problem, some peripheral edema, and a lot of breathlessness but with no underlying ischemia. “I use an ARA on these patients pretty quickly,” Dr. Jessup said. It’s best to start with a low dosage and see how the patient responds. “The best responders have a really stiff heart” and are usually not the more elderly HFpEF patients. ARA treatment also provides more steady volume control, superior to furosemide, she said.
Yet more additions
The revised guidelines contain even more changes. “We say that checking for anemia is important and how iron is an intervention that might make a difference,” said Dr. Jessup. Also, primary care physicians and cardiologists “should look for obstructive sleep apnea” in heart failure patients for whom “intervention with weight loss might help,” she said.
Another feature is the focus on tailored treatment, with many treatment elements that need customizing to each different type of heart failure patient. “Not every drug needs to be given to every patient,” Dr. Yancy warned.
The specifics of how to orchestrate all the guidelines into a coherent management plan may become clearer later this year, when the ACC/AHA group will release a follow-up “Heart Failure Pathways” document, aimed at bridging the gap between guidelines and actual clinical practice, Dr. Yancy said. “We want more value from writing the guidelines. The biggest obstacle is how to implement them,” and that’s what the pathways follow-up will address.
“The biggest challenge the societies have is how to motivate physicians and nurses to more aggressively treat heart failure,” said Dr. Butler.
Dr. Yancy and Dr. Jessup had no disclosures. Dr. Butler has been a consultant to 11 companies. Dr. Januzzi has been a consultant to Critical Diagnostics, Novartis, Phillips, Roche Diagnostics, and Sphingotec, and he has received research support from Amgen, Boehringer Ingelheim, Janssen, and Prevencio.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
Oral iron of no benefit in heart failure with iron deficiency
High-dose oral iron therapy doesn’t improve exercise capacity in the estimated 50% of patients with symptomatic heart failure who also have iron deficiency, according to a report published online May 16 in JAMA.
Iron deficiency in patients with HF, regardless of their hemoglobin status, is associated with reduced functional capacity, poorer quality of life, and increased mortality. Iron plays a crucial role in the delivery and utilization of oxygen, and “cells with high-energy demands, including skeletal and cardiac myocytes, are particularly sensitive to depleted iron stores,” said Gregory D. Lewis, MD, of the pulmonary critical care unit of Massachusetts General Hospital, Boston, and his associates.
The IRONOUT study was conducted at 23 U.S. medical centers, where outcomes after 16 weeks of oral iron therapy (150 mg twice daily) were compared against matching placebo in 225 patients. The median patient age was 63 years, and the median duration of HF was 5.7 years. Ischemic heart disease was the primary cause of HF in 78% of the study participants.
These patients had low LVEF and poor exercise capacity, despite having high rates of guideline-directed treatment with medications.
The primary endpoint was a change in peak oxygen uptake (peak VO2) at the conclusion of treatment, a measure that “reflects the multiple mechanisms by which iron repletion is expected to improve systemic oxygen delivery and utilization.” Change in peak VO2 was not significantly different between the 111 participants who took oral iron supplements (+23 mL/min) and the 114 who took placebo (–2 mL/min), the investigators wrote (JAMA Pediatr. 2017 May 16. doi: 10.1001/jama.2017.5427).
In subgroup analyses, oral iron also failed to improve peak VO2 in any subgroup of patients: neither men nor women; neither those with decreased hemoglobin nor those with normal hemoglobin levels; nor patients with or without venous congestion at baseline. Oral iron also failed to improve secondary endpoints including 6-minute walk distance, quality of life scores, NT-proBNP levels, and ventilatory efficiency.
In contrast to previous studies of IV iron repletion, oral iron supplementation “produced minimal improvement in iron stores, implicating the route of administration rather than the strategy of iron repletion in the lack of clinical benefit,” Dr. Lewis and his associates said.
This study was funded by the National Heart, Lung, and Blood Institute, which also conceived, designed, and conducted the trial. Dr. Lewis reported ties to Abbott, Novartis, Shape Systems, Stealth Bio Therapeutics, Ironwood, Cheetah Medical, Luitpold, and SoniVie. His associates reported ties to numerous industry sources.
High-dose oral iron therapy doesn’t improve exercise capacity in the estimated 50% of patients with symptomatic heart failure who also have iron deficiency, according to a report published online May 16 in JAMA.
Iron deficiency in patients with HF, regardless of their hemoglobin status, is associated with reduced functional capacity, poorer quality of life, and increased mortality. Iron plays a crucial role in the delivery and utilization of oxygen, and “cells with high-energy demands, including skeletal and cardiac myocytes, are particularly sensitive to depleted iron stores,” said Gregory D. Lewis, MD, of the pulmonary critical care unit of Massachusetts General Hospital, Boston, and his associates.
The IRONOUT study was conducted at 23 U.S. medical centers, where outcomes after 16 weeks of oral iron therapy (150 mg twice daily) were compared against matching placebo in 225 patients. The median patient age was 63 years, and the median duration of HF was 5.7 years. Ischemic heart disease was the primary cause of HF in 78% of the study participants.
These patients had low LVEF and poor exercise capacity, despite having high rates of guideline-directed treatment with medications.
The primary endpoint was a change in peak oxygen uptake (peak VO2) at the conclusion of treatment, a measure that “reflects the multiple mechanisms by which iron repletion is expected to improve systemic oxygen delivery and utilization.” Change in peak VO2 was not significantly different between the 111 participants who took oral iron supplements (+23 mL/min) and the 114 who took placebo (–2 mL/min), the investigators wrote (JAMA Pediatr. 2017 May 16. doi: 10.1001/jama.2017.5427).
In subgroup analyses, oral iron also failed to improve peak VO2 in any subgroup of patients: neither men nor women; neither those with decreased hemoglobin nor those with normal hemoglobin levels; nor patients with or without venous congestion at baseline. Oral iron also failed to improve secondary endpoints including 6-minute walk distance, quality of life scores, NT-proBNP levels, and ventilatory efficiency.
In contrast to previous studies of IV iron repletion, oral iron supplementation “produced minimal improvement in iron stores, implicating the route of administration rather than the strategy of iron repletion in the lack of clinical benefit,” Dr. Lewis and his associates said.
This study was funded by the National Heart, Lung, and Blood Institute, which also conceived, designed, and conducted the trial. Dr. Lewis reported ties to Abbott, Novartis, Shape Systems, Stealth Bio Therapeutics, Ironwood, Cheetah Medical, Luitpold, and SoniVie. His associates reported ties to numerous industry sources.
High-dose oral iron therapy doesn’t improve exercise capacity in the estimated 50% of patients with symptomatic heart failure who also have iron deficiency, according to a report published online May 16 in JAMA.
Iron deficiency in patients with HF, regardless of their hemoglobin status, is associated with reduced functional capacity, poorer quality of life, and increased mortality. Iron plays a crucial role in the delivery and utilization of oxygen, and “cells with high-energy demands, including skeletal and cardiac myocytes, are particularly sensitive to depleted iron stores,” said Gregory D. Lewis, MD, of the pulmonary critical care unit of Massachusetts General Hospital, Boston, and his associates.
The IRONOUT study was conducted at 23 U.S. medical centers, where outcomes after 16 weeks of oral iron therapy (150 mg twice daily) were compared against matching placebo in 225 patients. The median patient age was 63 years, and the median duration of HF was 5.7 years. Ischemic heart disease was the primary cause of HF in 78% of the study participants.
These patients had low LVEF and poor exercise capacity, despite having high rates of guideline-directed treatment with medications.
The primary endpoint was a change in peak oxygen uptake (peak VO2) at the conclusion of treatment, a measure that “reflects the multiple mechanisms by which iron repletion is expected to improve systemic oxygen delivery and utilization.” Change in peak VO2 was not significantly different between the 111 participants who took oral iron supplements (+23 mL/min) and the 114 who took placebo (–2 mL/min), the investigators wrote (JAMA Pediatr. 2017 May 16. doi: 10.1001/jama.2017.5427).
In subgroup analyses, oral iron also failed to improve peak VO2 in any subgroup of patients: neither men nor women; neither those with decreased hemoglobin nor those with normal hemoglobin levels; nor patients with or without venous congestion at baseline. Oral iron also failed to improve secondary endpoints including 6-minute walk distance, quality of life scores, NT-proBNP levels, and ventilatory efficiency.
In contrast to previous studies of IV iron repletion, oral iron supplementation “produced minimal improvement in iron stores, implicating the route of administration rather than the strategy of iron repletion in the lack of clinical benefit,” Dr. Lewis and his associates said.
This study was funded by the National Heart, Lung, and Blood Institute, which also conceived, designed, and conducted the trial. Dr. Lewis reported ties to Abbott, Novartis, Shape Systems, Stealth Bio Therapeutics, Ironwood, Cheetah Medical, Luitpold, and SoniVie. His associates reported ties to numerous industry sources.
Key clinical point: High-dose oral iron therapy doesn’t improve exercise capacity in the estimated 50% of patients with symptomatic heart failure and iron deficiency.
Major finding: Change in peak VO2 was not significantly different between the 111 participants who took oral iron supplements (+23 mL/min) and the 114 who took placebo (–2 mL/min).
Data source: A multicenter, randomized, double-blind, placebo-controlled phase II trial involving 225 patients treated for 16 weeks.
Disclosures: This study was funded by the National Heart, Lung, and Blood Institute (NCT02188784), which also conceived, designed, and conducted the trial. Dr. Lewis reported ties to Abbott, Novartis, Shape Systems, Stealth Bio Therapeutics, Ironwood, Cheetah Medical, Luitpold, and SoniVie. His associates reported ties to numerous industry sources.
PPIs triple heart failure hospitalization risk in atrial fib patients
PARIS – Unwarranted prescriptions for proton pump inhibitors tripled the rate at which patients with atrial fibrillation needed hospitalization for a first episode of acute heart failure, in a retrospective study of 172 patients at a single center in Portugal.
About a third of the atrial fibrillation patients received a proton pump inhibitor (PPI) without a clear indication, and the PPI recipients developed heart failure at 2.9 times the rate as patients not on a PPI, a statistically significant difference, João B. Augusto, MD, reported at a meeting held by the Heart Failure Association of the European Society of Cardiology. Dr. Augusto believes that these patients largely had no need for PPI treatment, and the drug may have cut iron and vitamin B12 absorption by lowering gastric acid, resulting in deficiencies that produced anemia, and following that, heart failure, he suggested.
The study focused on 423 patients admitted to Fernando da Fonseca Hospital during January 2014–June 2015 with a primary or secondary diagnosis of atrial fibrillation. He excluded 101 patients with a history of heart failure, 109 patients on antiplatelet therapy, and 33 patients with a clear need for PPI treatment because of a gastrointestinal condition. Another 11 patients were lost to follow-up, leaving 172 patients followed for 1 year.
At the time of their initial hospitalization, 53 patients (31%) received a prescription for a PPI despite having no gastrointestinal diagnosis, likely a prophylactic step for patients receiving an oral anticoagulant, Dr. Augusto said. The patients averaged 69 years old, and nearly two-thirds were men.
During 1-year follow-up, the incidence of hospitalization for acute heart failure was 8% in the patients not on a PPI and 23% among those on a PPI, a statistically significant difference. In a regression analysis that controlled for age and chronic kidney disease, the incidence of acute heart failure was 2.9 times more common among patients on a PPI, Dr. Augusto said. He and his associates used these findings to educate their hospital’s staff to not needlessly prescribe a PPI to atrial fibrillation patients.
Dr. Augusto had no disclosures.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
PARIS – Unwarranted prescriptions for proton pump inhibitors tripled the rate at which patients with atrial fibrillation needed hospitalization for a first episode of acute heart failure, in a retrospective study of 172 patients at a single center in Portugal.
About a third of the atrial fibrillation patients received a proton pump inhibitor (PPI) without a clear indication, and the PPI recipients developed heart failure at 2.9 times the rate as patients not on a PPI, a statistically significant difference, João B. Augusto, MD, reported at a meeting held by the Heart Failure Association of the European Society of Cardiology. Dr. Augusto believes that these patients largely had no need for PPI treatment, and the drug may have cut iron and vitamin B12 absorption by lowering gastric acid, resulting in deficiencies that produced anemia, and following that, heart failure, he suggested.
The study focused on 423 patients admitted to Fernando da Fonseca Hospital during January 2014–June 2015 with a primary or secondary diagnosis of atrial fibrillation. He excluded 101 patients with a history of heart failure, 109 patients on antiplatelet therapy, and 33 patients with a clear need for PPI treatment because of a gastrointestinal condition. Another 11 patients were lost to follow-up, leaving 172 patients followed for 1 year.
At the time of their initial hospitalization, 53 patients (31%) received a prescription for a PPI despite having no gastrointestinal diagnosis, likely a prophylactic step for patients receiving an oral anticoagulant, Dr. Augusto said. The patients averaged 69 years old, and nearly two-thirds were men.
During 1-year follow-up, the incidence of hospitalization for acute heart failure was 8% in the patients not on a PPI and 23% among those on a PPI, a statistically significant difference. In a regression analysis that controlled for age and chronic kidney disease, the incidence of acute heart failure was 2.9 times more common among patients on a PPI, Dr. Augusto said. He and his associates used these findings to educate their hospital’s staff to not needlessly prescribe a PPI to atrial fibrillation patients.
Dr. Augusto had no disclosures.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
PARIS – Unwarranted prescriptions for proton pump inhibitors tripled the rate at which patients with atrial fibrillation needed hospitalization for a first episode of acute heart failure, in a retrospective study of 172 patients at a single center in Portugal.
About a third of the atrial fibrillation patients received a proton pump inhibitor (PPI) without a clear indication, and the PPI recipients developed heart failure at 2.9 times the rate as patients not on a PPI, a statistically significant difference, João B. Augusto, MD, reported at a meeting held by the Heart Failure Association of the European Society of Cardiology. Dr. Augusto believes that these patients largely had no need for PPI treatment, and the drug may have cut iron and vitamin B12 absorption by lowering gastric acid, resulting in deficiencies that produced anemia, and following that, heart failure, he suggested.
The study focused on 423 patients admitted to Fernando da Fonseca Hospital during January 2014–June 2015 with a primary or secondary diagnosis of atrial fibrillation. He excluded 101 patients with a history of heart failure, 109 patients on antiplatelet therapy, and 33 patients with a clear need for PPI treatment because of a gastrointestinal condition. Another 11 patients were lost to follow-up, leaving 172 patients followed for 1 year.
At the time of their initial hospitalization, 53 patients (31%) received a prescription for a PPI despite having no gastrointestinal diagnosis, likely a prophylactic step for patients receiving an oral anticoagulant, Dr. Augusto said. The patients averaged 69 years old, and nearly two-thirds were men.
During 1-year follow-up, the incidence of hospitalization for acute heart failure was 8% in the patients not on a PPI and 23% among those on a PPI, a statistically significant difference. In a regression analysis that controlled for age and chronic kidney disease, the incidence of acute heart failure was 2.9 times more common among patients on a PPI, Dr. Augusto said. He and his associates used these findings to educate their hospital’s staff to not needlessly prescribe a PPI to atrial fibrillation patients.
Dr. Augusto had no disclosures.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
AT HEART FAILURE 2017
Key clinical point:
Major finding: Atrial fibrillation patients had a 2.9 times higher acute heart failure rate on a proton pump inhibitor, compared with no PPI.
Data source: Retrospective review of 172 atrial fibrillation patients seen during 2014-2015 at a single center in Portugal.
Disclosures: Dr. Augusto had no disclosures.
Bromocriptine shows efficacy, safety for peripartum cardiomyopathy
PARIS – Two regimens of bromocriptine treatment administered with anticoagulation and standard heart failure management were safe, and often effective, for normalizing ejection fraction levels in women diagnosed with peripartum cardiomyopathy in a study with 63 women and designed to be the pivotal trial for this management strategy.
“Bromocriptine therapy applied for 1 week seems sufficient to promote healing from PPCM [peripartum cardiomyopathy] in most patients, although critically ill patients may profit from prolonged [8 week] treatment,” Denise Hilfiker-Kleiner, PhD, said at a meeting of the Heart Failure Association of the ESC.
Women who are suspected of having PPCM but with less compromised ventricular output, with an ejection fraction of 40%-45%, should be closely followed with repeated clinical examinations for 6 months and echocardiography examinations at 3 and 6 months to see if their cardiac output worsens enough to justify initiating a bromocriptine regimen, she advised. “We don’t recommend that every woman with an postpartum ejection fraction of 45% needs to immediately stop lactation [with bromocriptine treatment], but she should be frequently seen by a cardiologist to see whether she recovers or deteriorates further.”
The PPCM (Effect of Bromocriptine on Left Ventricular Function in Women With Peripartum Cardiomyopathy) trial enrolled 63 women with PPCM and severely depressed left ventricular ejection fraction at 12 German centers. Randomization placed 32 women into a group assigned to received 1 week of bromocriptine treatment, with 26 completing the study, and 31 in a group treated with bromocriptine for 8 weeks, with all 31 completing the study. The patients averaged 34 years of age. All patients also received standard heart failure treatment.
The study’s primary endpoint, the change in left ventricular ejection fraction from baseline to 6-month follow-up, was similar in the two treatment groups, with the 1-week regimen leading to an average 21% improvement in ejection fraction and the 8-week regimen averaging a 24% gain in pump function. Among a subgroup of 37 women who entered the study with a left ventricular ejection fraction of less than 30%, slightly more than 60% achieved full heart function by 6-month follow-up with an ejection fraction of 50% or greater, and an additional 35% had partial recovery, with a follow-up ejection fraction of 35%-49%, Dr. Hilfiker-Kleiner reported.
No women in the study developed a thrombotic complication, a potential danger of the bromocriptine intervention. All participants received antithrombotic prophylaxis with either warfarin or subcutaneous heparin. Although the bromocriptine strategy has already been adopted for routine treatment of PPCM in Germany and in many other parts of the world, its uptake in the United States has lagged, largely because of concerns about thrombotic complications, noted Dr. Sliwa, professor of medicine and director of the Hatter Institute for Cardiovascular Research in Africa at the University of Cape Town, South Africa.
Among all 57 women available for a follow-up echocardiography assessment 6 months after the start of treatment, roughly 60% had a left ventricular ejection fraction of 50% or greater, and more than 20% achieved an ejection fraction of 35%-49%. The remaining roughly 18% of women either did not have a 6-month follow-up or failed to reach at least a 35% ejection fraction at 6 months.
PPCM can be a diagnostic challenge, said Dr. Hilfiker-Kleiner, but it is relatively common, with an average worldwide incidence of about 1 case for every 1,000 deliveries. The incidence may be even higher with many cases going undetected, often because the clinical signs of PPCM, including fatigue, difficulty sleeping, edema, and dyspnea, can be dismissed as the results of recent pregnancy or caring for a newborn baby. Certain racial or ethnic groups appear to have an increased incidence of the disease, including African and Hispanic women, likely because of genetic factors, said Dr. Sliwa. Clinical factors that boost risk include pre-eclampsia, smoking, obesity, older age, and multiparity, but not diabetes.
Testing for N-terminal-pro B-type natriuretic peptide levels appears to be a good screen for women who have developed PPCM, with a level of at least 500 pg/mL high enough to warrant further assessment, Dr. Sliwa said. She recommended running an NT-proBNP test on any recent postpartum women with a clinical or demographic risk factor or suggestive clinical presentation, but she also stressed that PPCM can occur in younger, totally healthy, and athletic women who appear to have a normal delivery.
A significant concern about bromocriptine treatment is that it precludes breastfeeding, a reason not to use the drug in women with an ejection fraction of 40% or greater, especially in settings where access to safe baby formula is a challenge.
The PPCM trial enrolled 63 women at 12 German centers.
The trial received no commercial funding. Dr. Hilfiker-Kleiner and Dr. Sliwa had no disclosures.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
This is a very important trial that was extremely difficult to conduct, and the results are exciting. It represents an effective bedside to bench to bedside sequence of research. The problem of peripartum cardiomyopathy was recognized in clinical practice, understood through basic research that led to a potential treatment, and the treatment is now confirmed through clinical testing. The results provide a reason for hope for the women who develop this disease.
These trial results are important for all mothers, for all women, and for anyone born from a woman.
Mariell Jessup, MD, is a heart failure specialist and chief scientific officer of the Leducq organization in Boston. She had no disclosures. She made these comments as designated discussant for the report by Dr. Hilfiker-Kleiner.
This is a very important trial that was extremely difficult to conduct, and the results are exciting. It represents an effective bedside to bench to bedside sequence of research. The problem of peripartum cardiomyopathy was recognized in clinical practice, understood through basic research that led to a potential treatment, and the treatment is now confirmed through clinical testing. The results provide a reason for hope for the women who develop this disease.
These trial results are important for all mothers, for all women, and for anyone born from a woman.
Mariell Jessup, MD, is a heart failure specialist and chief scientific officer of the Leducq organization in Boston. She had no disclosures. She made these comments as designated discussant for the report by Dr. Hilfiker-Kleiner.
This is a very important trial that was extremely difficult to conduct, and the results are exciting. It represents an effective bedside to bench to bedside sequence of research. The problem of peripartum cardiomyopathy was recognized in clinical practice, understood through basic research that led to a potential treatment, and the treatment is now confirmed through clinical testing. The results provide a reason for hope for the women who develop this disease.
These trial results are important for all mothers, for all women, and for anyone born from a woman.
Mariell Jessup, MD, is a heart failure specialist and chief scientific officer of the Leducq organization in Boston. She had no disclosures. She made these comments as designated discussant for the report by Dr. Hilfiker-Kleiner.
PARIS – Two regimens of bromocriptine treatment administered with anticoagulation and standard heart failure management were safe, and often effective, for normalizing ejection fraction levels in women diagnosed with peripartum cardiomyopathy in a study with 63 women and designed to be the pivotal trial for this management strategy.
“Bromocriptine therapy applied for 1 week seems sufficient to promote healing from PPCM [peripartum cardiomyopathy] in most patients, although critically ill patients may profit from prolonged [8 week] treatment,” Denise Hilfiker-Kleiner, PhD, said at a meeting of the Heart Failure Association of the ESC.
Women who are suspected of having PPCM but with less compromised ventricular output, with an ejection fraction of 40%-45%, should be closely followed with repeated clinical examinations for 6 months and echocardiography examinations at 3 and 6 months to see if their cardiac output worsens enough to justify initiating a bromocriptine regimen, she advised. “We don’t recommend that every woman with an postpartum ejection fraction of 45% needs to immediately stop lactation [with bromocriptine treatment], but she should be frequently seen by a cardiologist to see whether she recovers or deteriorates further.”
The PPCM (Effect of Bromocriptine on Left Ventricular Function in Women With Peripartum Cardiomyopathy) trial enrolled 63 women with PPCM and severely depressed left ventricular ejection fraction at 12 German centers. Randomization placed 32 women into a group assigned to received 1 week of bromocriptine treatment, with 26 completing the study, and 31 in a group treated with bromocriptine for 8 weeks, with all 31 completing the study. The patients averaged 34 years of age. All patients also received standard heart failure treatment.
The study’s primary endpoint, the change in left ventricular ejection fraction from baseline to 6-month follow-up, was similar in the two treatment groups, with the 1-week regimen leading to an average 21% improvement in ejection fraction and the 8-week regimen averaging a 24% gain in pump function. Among a subgroup of 37 women who entered the study with a left ventricular ejection fraction of less than 30%, slightly more than 60% achieved full heart function by 6-month follow-up with an ejection fraction of 50% or greater, and an additional 35% had partial recovery, with a follow-up ejection fraction of 35%-49%, Dr. Hilfiker-Kleiner reported.
No women in the study developed a thrombotic complication, a potential danger of the bromocriptine intervention. All participants received antithrombotic prophylaxis with either warfarin or subcutaneous heparin. Although the bromocriptine strategy has already been adopted for routine treatment of PPCM in Germany and in many other parts of the world, its uptake in the United States has lagged, largely because of concerns about thrombotic complications, noted Dr. Sliwa, professor of medicine and director of the Hatter Institute for Cardiovascular Research in Africa at the University of Cape Town, South Africa.
Among all 57 women available for a follow-up echocardiography assessment 6 months after the start of treatment, roughly 60% had a left ventricular ejection fraction of 50% or greater, and more than 20% achieved an ejection fraction of 35%-49%. The remaining roughly 18% of women either did not have a 6-month follow-up or failed to reach at least a 35% ejection fraction at 6 months.
PPCM can be a diagnostic challenge, said Dr. Hilfiker-Kleiner, but it is relatively common, with an average worldwide incidence of about 1 case for every 1,000 deliveries. The incidence may be even higher with many cases going undetected, often because the clinical signs of PPCM, including fatigue, difficulty sleeping, edema, and dyspnea, can be dismissed as the results of recent pregnancy or caring for a newborn baby. Certain racial or ethnic groups appear to have an increased incidence of the disease, including African and Hispanic women, likely because of genetic factors, said Dr. Sliwa. Clinical factors that boost risk include pre-eclampsia, smoking, obesity, older age, and multiparity, but not diabetes.
Testing for N-terminal-pro B-type natriuretic peptide levels appears to be a good screen for women who have developed PPCM, with a level of at least 500 pg/mL high enough to warrant further assessment, Dr. Sliwa said. She recommended running an NT-proBNP test on any recent postpartum women with a clinical or demographic risk factor or suggestive clinical presentation, but she also stressed that PPCM can occur in younger, totally healthy, and athletic women who appear to have a normal delivery.
A significant concern about bromocriptine treatment is that it precludes breastfeeding, a reason not to use the drug in women with an ejection fraction of 40% or greater, especially in settings where access to safe baby formula is a challenge.
The PPCM trial enrolled 63 women at 12 German centers.
The trial received no commercial funding. Dr. Hilfiker-Kleiner and Dr. Sliwa had no disclosures.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
PARIS – Two regimens of bromocriptine treatment administered with anticoagulation and standard heart failure management were safe, and often effective, for normalizing ejection fraction levels in women diagnosed with peripartum cardiomyopathy in a study with 63 women and designed to be the pivotal trial for this management strategy.
“Bromocriptine therapy applied for 1 week seems sufficient to promote healing from PPCM [peripartum cardiomyopathy] in most patients, although critically ill patients may profit from prolonged [8 week] treatment,” Denise Hilfiker-Kleiner, PhD, said at a meeting of the Heart Failure Association of the ESC.
Women who are suspected of having PPCM but with less compromised ventricular output, with an ejection fraction of 40%-45%, should be closely followed with repeated clinical examinations for 6 months and echocardiography examinations at 3 and 6 months to see if their cardiac output worsens enough to justify initiating a bromocriptine regimen, she advised. “We don’t recommend that every woman with an postpartum ejection fraction of 45% needs to immediately stop lactation [with bromocriptine treatment], but she should be frequently seen by a cardiologist to see whether she recovers or deteriorates further.”
The PPCM (Effect of Bromocriptine on Left Ventricular Function in Women With Peripartum Cardiomyopathy) trial enrolled 63 women with PPCM and severely depressed left ventricular ejection fraction at 12 German centers. Randomization placed 32 women into a group assigned to received 1 week of bromocriptine treatment, with 26 completing the study, and 31 in a group treated with bromocriptine for 8 weeks, with all 31 completing the study. The patients averaged 34 years of age. All patients also received standard heart failure treatment.
The study’s primary endpoint, the change in left ventricular ejection fraction from baseline to 6-month follow-up, was similar in the two treatment groups, with the 1-week regimen leading to an average 21% improvement in ejection fraction and the 8-week regimen averaging a 24% gain in pump function. Among a subgroup of 37 women who entered the study with a left ventricular ejection fraction of less than 30%, slightly more than 60% achieved full heart function by 6-month follow-up with an ejection fraction of 50% or greater, and an additional 35% had partial recovery, with a follow-up ejection fraction of 35%-49%, Dr. Hilfiker-Kleiner reported.
No women in the study developed a thrombotic complication, a potential danger of the bromocriptine intervention. All participants received antithrombotic prophylaxis with either warfarin or subcutaneous heparin. Although the bromocriptine strategy has already been adopted for routine treatment of PPCM in Germany and in many other parts of the world, its uptake in the United States has lagged, largely because of concerns about thrombotic complications, noted Dr. Sliwa, professor of medicine and director of the Hatter Institute for Cardiovascular Research in Africa at the University of Cape Town, South Africa.
Among all 57 women available for a follow-up echocardiography assessment 6 months after the start of treatment, roughly 60% had a left ventricular ejection fraction of 50% or greater, and more than 20% achieved an ejection fraction of 35%-49%. The remaining roughly 18% of women either did not have a 6-month follow-up or failed to reach at least a 35% ejection fraction at 6 months.
PPCM can be a diagnostic challenge, said Dr. Hilfiker-Kleiner, but it is relatively common, with an average worldwide incidence of about 1 case for every 1,000 deliveries. The incidence may be even higher with many cases going undetected, often because the clinical signs of PPCM, including fatigue, difficulty sleeping, edema, and dyspnea, can be dismissed as the results of recent pregnancy or caring for a newborn baby. Certain racial or ethnic groups appear to have an increased incidence of the disease, including African and Hispanic women, likely because of genetic factors, said Dr. Sliwa. Clinical factors that boost risk include pre-eclampsia, smoking, obesity, older age, and multiparity, but not diabetes.
Testing for N-terminal-pro B-type natriuretic peptide levels appears to be a good screen for women who have developed PPCM, with a level of at least 500 pg/mL high enough to warrant further assessment, Dr. Sliwa said. She recommended running an NT-proBNP test on any recent postpartum women with a clinical or demographic risk factor or suggestive clinical presentation, but she also stressed that PPCM can occur in younger, totally healthy, and athletic women who appear to have a normal delivery.
A significant concern about bromocriptine treatment is that it precludes breastfeeding, a reason not to use the drug in women with an ejection fraction of 40% or greater, especially in settings where access to safe baby formula is a challenge.
The PPCM trial enrolled 63 women at 12 German centers.
The trial received no commercial funding. Dr. Hilfiker-Kleiner and Dr. Sliwa had no disclosures.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
AT HEART FAILURE 2017
Key clinical point:
Major finding: At 6-month follow-up, more than 80% of patients had full or partial restoration of their left ventricular function.
Data source: The PPCM trial, which enrolled 63 women at 12 German centers.
Disclosures: The trial received no commercial funding. Dr. Hilfiker-Kleiner and Dr. Sliwa had no disclosures.