Assessing A-HeFT and PEACE Eric J Topol MD Provost and Chief Academic Officer Chair, Department of...
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Transcript of Assessing A-HeFT and PEACE Eric J Topol MD Provost and Chief Academic Officer Chair, Department of...
![Page 1: Assessing A-HeFT and PEACE Eric J Topol MD Provost and Chief Academic Officer Chair, Department of Cardiovascular Medicine Cleveland Clinic Foundation.](https://reader036.fdocuments.net/reader036/viewer/2022083007/56649e585503460f94b50e48/html5/thumbnails/1.jpg)
Assessing A-HeFT and PEACE
Eric J Topol MDProvost and Chief Academic OfficerChair, Department of Cardiovascular MedicineCleveland Clinic FoundationCleveland, OH
Robert M Califf MDProfessor of MedicineAssociate Vice Chancellor for Clinical ResearchDirector, Duke Clinical Research InstituteDuke University Medical CenterDurham, NC
![Page 2: Assessing A-HeFT and PEACE Eric J Topol MD Provost and Chief Academic Officer Chair, Department of Cardiovascular Medicine Cleveland Clinic Foundation.](https://reader036.fdocuments.net/reader036/viewer/2022083007/56649e585503460f94b50e48/html5/thumbnails/2.jpg)
African-American Heart Failure Trial (A-HeFT)
![Page 3: Assessing A-HeFT and PEACE Eric J Topol MD Provost and Chief Academic Officer Chair, Department of Cardiovascular Medicine Cleveland Clinic Foundation.](https://reader036.fdocuments.net/reader036/viewer/2022083007/56649e585503460f94b50e48/html5/thumbnails/3.jpg)
A-HeFT design
• Randomized 1050 men and women who classified themselves as African American
• Patients had NYHA class 3-4 HF and reduced LV function
• Received a fixed-dose combination of isosorbide dinitrate-hydralazine or placebo
![Page 4: Assessing A-HeFT and PEACE Eric J Topol MD Provost and Chief Academic Officer Chair, Department of Cardiovascular Medicine Cleveland Clinic Foundation.](https://reader036.fdocuments.net/reader036/viewer/2022083007/56649e585503460f94b50e48/html5/thumbnails/4.jpg)
A-HeFT halted early
• The trial was terminated before the planned 1100 patients had been randomized
• Significant mortality increase observed in the placebo group
• There was a 43% reduction in mortality in the group given isosorbide dinitrate plus hydralazine
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Outcomes of the primary composite end point and its components
End point ISDN-hydralazine (n=518)
Placebo (n=532)
p
Primary end point composite score
-0.1 -0.5 0.01
All-cause mortality 6.2% 10.2% 0.02
First HF hospitalization
16.4% 24.4% 0.001
Change in quality-of-life score at 6 months
-5.5 -2.7 0.02
![Page 6: Assessing A-HeFT and PEACE Eric J Topol MD Provost and Chief Academic Officer Chair, Department of Cardiovascular Medicine Cleveland Clinic Foundation.](https://reader036.fdocuments.net/reader036/viewer/2022083007/56649e585503460f94b50e48/html5/thumbnails/6.jpg)
A-HeFT
"A magnificent effort."
"This trial will set a lot of precedents."
Califf
![Page 7: Assessing A-HeFT and PEACE Eric J Topol MD Provost and Chief Academic Officer Chair, Department of Cardiovascular Medicine Cleveland Clinic Foundation.](https://reader036.fdocuments.net/reader036/viewer/2022083007/56649e585503460f94b50e48/html5/thumbnails/7.jpg)
A-HeFT
"A stepping stone to identifying what is the genomic basis for this extraordinary benefit."
"Should we be prescribing these to all black patients with heart failure today?"
Topol
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How to apply the results
• This combination should be added to existing treatments in African Americans with heart failure
• It is premature to take this action in non-African Americans
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A-HeFT
"It's a very interesting trial—it's one of a kind. I don't know if there's ever been a cardiovascular medical trial like this one."
"I would certainly give it two thumbs up for identifying a very important life-saving effect."
Topol
![Page 10: Assessing A-HeFT and PEACE Eric J Topol MD Provost and Chief Academic Officer Chair, Department of Cardiovascular Medicine Cleveland Clinic Foundation.](https://reader036.fdocuments.net/reader036/viewer/2022083007/56649e585503460f94b50e48/html5/thumbnails/10.jpg)
A-HeFT
"I give it two thumbs up too for all of the reasons that you just gave."
Califf
![Page 11: Assessing A-HeFT and PEACE Eric J Topol MD Provost and Chief Academic Officer Chair, Department of Cardiovascular Medicine Cleveland Clinic Foundation.](https://reader036.fdocuments.net/reader036/viewer/2022083007/56649e585503460f94b50e48/html5/thumbnails/11.jpg)
Prevention of Events with Angiotensin-Converting Enzyme Inhibition
(PEACE)
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PEACE design
• Would patients with stable coronary artery disease but normal or slightly reduced LVF derive benefit from the addition of ACE inhibitors to conventional therapy?
• Randomized, double-blind, placebo-controlled study of 8290 patients
• Patients received either trandolapril 4 mg/day or placebo
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Findings
• The incidence of the primary end point—a composite of cardiovascular mortality, nonfatal MI, and coronary revascularization—was nearly identical in the two study arms
• After an average follow-up of 4.8 years, no subgroup benefited from ACE-inhibitor therapy
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Incidence of the primary end point and components
Outcome Trandolapril (n=4158) (%)
Placebo (n=4132) (%)
Hazard ratio (95% CI)
p
Primary end point
21.9 22.5 0.96 (0.88-1.06)
0.43
Death from noncardio-vascular causes
3.7 4.4 0.83 (0.67-1.03)
0.09
All-cause mortality
7.2 8.1 0.89 (0.76-1.04)
0.13
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Previous trials
Heart Outcomes Prevention Evaluation (HOPE)
and
European Trial on Reduction of Cardiac Events with Perindopril in Stable Coronary Artery Disease
(EUROPA)
High-risk coronary patients could gain additional cardiovascular protection with an
ACE inhibitor
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Evaluating PEACE
"When you have two trials that show a significant benefit with pretty much a similar construct as PEACE, you wonder about the third trial."
"Perhaps [this is due to] the fact that it is a much lower-risk population and the power of this trial is less than the other two."
Topol
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Evaluating PEACE
Possible explanations for the differences between trials:
• Lower-risk patient cohort limited the power of the trial
• Different ACE inhibitor with perhaps a different benefit
• More robust background treatment
• Bad luck?
Califf
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Applying PEACE
• ACE inhibitors can be crossed off the required list for patients with coronary disease and good LV function
• Potentially welcome news in reducing the pharmaceutical toll on patients
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PEACE
"I'm only going to give PEACE one thumb up."
"I give the investigators and the originators of PEACE two thumbs up—it was the right question and a very gritty hard-fought-out trial."
"I'm going to give the NHLBI only one thumb up for not supporting it with enough money to get it done quickly."
Califf
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PEACE
"I think that's the problem here. I think the trial went on for a long time and wound up with, unfortunately, a pretty low-risk population at entry and it's a little more difficult to interpret."
"I tend to agree with that assessment."
Topol