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Published byReginald Burns Modified over 9 years ago
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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
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African-American Heart Failure Trial (A-HeFT)
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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
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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 pointISDN- hydralazine (n=518) Placebo (n=532) p Primary end point composite score -0.1-0.50.01 All-cause mortality6.2%10.2%0.02 First HF hospitalization 16.4%24.4%0.001 Change in quality- of-life score at 6 months -5.5-2.70.02
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A-HeFT "A magnificent effort." "This trial will set a lot of precedents." Califf
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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
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A-HeFT "I give it two thumbs up too for all of the reasons that you just gave." Califf
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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 OutcomeTrandolapril (n=4158) (%) Placebo (n=4132) (%) Hazard ratio (95% CI) p Primary end point 21.922.50.96 (0.88-1.06) 0.43 Death from noncardio- vascular causes 3.74.40.83 (0.67-1.03) 0.09 All-cause mortality 7.28.10.89 (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
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