1. In patients with congestive heart failure, the combination of hydralazine and isosorbide dinitrate significantly reduced mortality when compared with placebo.
2. This was one of the first large, randomized trials to demonstrate significant mortality benefit in the treatment of congestive heart failure.
Original Date of Publication: June 1986
Study Rundown: Prior to the 1980s, few options were available in heart failure treatment, with digitalis and diuretics being the only medications used to relieve symptoms. Subsequent efforts to treat heart failure focused on altering hemodynamics, and it was hypothesized that reducing preload and afterload using isosorbide dinitrate and hydralazine, respectively, could improve outcomes. The Vasodilator-Heart Failure Trial I (V-HeFT I) sought to explore the effects of using a combination of hydralazine and isosorbide dinitrate in managing heart failure. In summary, this trial demonstrated that treating patients with congestive heart failure with hydralazine-isosorbide dinitrate significantly reduced mortality when compared with placebo for the initial 3-year period. This study was one of the first to demonstrate a significant reduction in mortality with heart failure treatment.
In-Depth [randomized controlled trial]: This study, originally published in NEJM in 1986, randomized 642 patients to treatment with placebo, prazosin 2.5 mg QID, or hydralazine 37.5 mg-isosorbide dinitrate 20 mg QID. Patients with chronic congestive heart failure were recruited from 11 Veterans Administration hospitals in the United States. Patients were eligible for the trial if they were male, between 18-75 years of age, and had congestive heart failure, as determined by evidence of cardiac dilatation (i.e., increased cardiothoracic size on chest x-ray, left ventricular dilatation on echocardiogram) or left ventricular impairment and reduced exercise tolerance. Patients were excluded if they had reduced exercise tolerance due to chest pain, rather than fatigue/breathlessness, myocardial infarction in the recent 3 months, or substantial disease to limit 5-year survival.
Over the initial 2-year period, Cox regression demonstrated a significant 34% reduction in mortality in the hydralazine-isosorbide dinitrate group compared with the placebo group (95%CI 4-54%). By 3 years, the hydralazine-isosorbide dintrate group experienced a 36% reduction in mortality (95%CI 11-54%). Beyond 3 years, the data was insufficient to draw any conclusions.
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