Assessing A-HeFT and PEACE
Eric J Topol MD Provost and Chief Academic Officer Chair, Department of Cardiovascular Medicine Cleveland Clinic Foundation Cleveland, OH
Robert M Califf MD Professor of Medicine Associate Vice Chancellor for Clinical Research Director, Duke Clinical Research Institute Duke University Medical Center Durham, NC
African-American Heart Failure Trial (A-HeFT)
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
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
Outcomes of the primary composite end point and its components
A-HeFT
"A magnificent effort."
"This trial will set a lot of precedents."
Califf
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
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
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
A-HeFT
"I give it two thumbs up too for all of the reasons that you just gave."
Califf
Prevention of Events with Angiotensin-Converting Enzyme Inhibition (PEACE)
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
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
Incidence of the primary end point and components
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
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
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
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
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
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