Clinical Trials
African-American Heart Failure Trial (A-HeFT): Rationale, design, and methodology*,**

https://doi.org/10.1054/jcaf.2002.124730Get rights and content

Abstract

Background: Hydralazine and isosorbide dinitrate combination (H+ISDN), angiotensin-converting enzyme inhibitors, and beta-blockers have improved outcomes in heart failure (HF). Analysis of previous trials has shown that H+ISDN appears especially beneficial in African American patients. Methods and Results: The African-American Heart Failure Trial (A-HeFT) is double-blind, placebo-controlled, and includes African American patients with stable New York Heart Association Class III-IV HF on standard therapy. Patients must have prior HF-related events and left ventricular ejection fraction (LVEF) ≤35% or LVEF <45% with left ventricular internal diastolic dimension >2.9 cm/m2. Randomization to addition of placebo or BiDil (Nitro Med, Inc., Bedford, MA), a fixed combination of H+ISDN, is stratified for beta-blocker usage. All patients are treated and followed until the last patient entered completes 6 months of follow-up. The primary efficacy endpoint is a composite score including quality of life, death, and hospitalization for HF. At least 600 patients will be randomized; the first was randomized in June 2001. Conclusions: In addition to providing additional information on BiDil efficacy in HF, A-HeFT is the first HF trial aimed at a selected subgroup of patients and the first to use a new composite HF score as its primary efficacy endpoint.

Section snippets

Ethics and informed consent

The final study protocol was reviewed and approved by appropriate Institutional Review Boards, and all patients must give written informed consent before the performance of any screening procedures.

Study population

Patients are male or female at least 18 years old and African American by self-declaration. They must have HF diagnosed for at least 3 months, with New York Heart Association (NYHA) Class III-IV symptoms at screening while receiving a stable therapeutic regimen for HF. There is no prespecified

Endpoints

The primary efficacy variable is a composite score of clinical outcomes including death, first hospitalization for HF, and QOL measured at 6 months. The scoring system is shown in Table 2.

. Composite scoring system for A-HeFT

Variable ScoredCriteriaScore
DeathDeath from any cause anytime during trial−3
Alive at end of trial0
HospitalizationA first hospitalization for heart failure−1
No hospitalization for heart failure0
Change in Quality of Life at 6 months*Reduction by −10 or more units = markedly

Preliminary recruitment experience

The first patient was randomized into the trial in June 2001. As of March 1, 2002, 207 patients have been randomized. Given the small number of patients currently entered, it is premature to provide any of their baseline demographics or HF historical data because they may not be a representative sample.

Discussion

The overall efficacy of the free combination of H+ISDN has been established by the V-HeFT trials. The V-HeFT I trial demonstrated its beneficial effect on survival compared to placebo or prazosin, and V-HeFT II observed the same mortality rate on H+ISDN, though this effect was not as good as that of enalapril.4, 5 However, H+ISDN was more effective than enalapril on exercise capacity and QOL. Taken together these results indicate that H+ISDN produces beneficial effects in the broad population

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    *

    Reprint requests: Joseph A. Franciosa, MD, 350 East 79th Street, Apartment 39C, New York, NY 10021.

    **

    Supported by a grant from NitroMed Inc, Bedford, Massachusetts.

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