"Vasodilator Therapy for Chronic Congestive Heart Failure".The New England Journal of Medicine. 1986. 314(24):1547–1552.PubMed•Full text•PDFContents1Clinical Question2Bottom Line3Major Points4Guidelines5Design6Population6.1Inclusion Criteria6.2Exclusion Criteria6.3Baseline Characteristics7Interventions8Outcomes8.1Primary Outcomes8.2Secondary Outcomes9Funding10Further ReadingClinical QuestionDoes the addition of hydralazine and isosorbide dinitrate to the therapeutic regimen of digoxin and diuretics improve mortality outcomes in patients with chronic congestive heart failure?Bottom LineThe addition of hydralazine and isosorbide dinitrate to conventional therapy with digoxin and diuretics in patients with chronic congestive heart failure appeared to decrease mortality rates at two years and may improve left ventricular function.Major PointsVasodilator therapy has demonstrated favorable hemodynamic responses in patients with congestive heart failure, but its effect on mortality had not been well-studied prior to this trial. The Veterans Administration Cooperative Study, initiated in 1980, examined whether prazosin alone or the combination therapy of hydralazine and isosorbide dinitrate could improve life expectancy in men with stable chronic congestive heart failure on a background of digoxin and diuretics. The study found a decrease in mortality with the combination therapy at two years compared to placebo, although the overall follow-up showed only borderline statistical significance for mortality reduction.GuidelinesAs of this trial publication in 1986, there were no established guidelines reflecting the results of this trial.DesignMulticenter, double-blind, randomized, placebo-controlled trial.N=642 men with chronic congestive heart failure.Interventions:Placebo (n=273)Prazosin 20 mg/day (n=183)Hydralazine 300 mg/day and isosorbide dinitrate 160 mg/day (n=186)Setting: 11 Veterans Administration hospitals.Enrollment: March 1980 - June 1985.Follow-up: Mean 2.3 years (range 6 months to 5.7 years).Primary outcome: Mortality from all causes.PopulationInclusion CriteriaMen aged 18-75 with chronic congestive heart failure.Cardiac dilatation or left ventricular impairment.Reduced exercise tolerance as assessed by maximal bicycle-ergometer exercise test.Stable and optimally treated with digoxin and diuretics.Exclusion CriteriaExercise tolerance limited by chest pain rather than breathlessness or fatigue.Myocardial infarction within the previous three months.Significant obstructive valvular or myocardial disease, chronic pulmonary disease, or other diseases limiting survival.Need for long-acting nitrates, calcium antagonists, beta-blockers, or antihypertensive drugs other than diuretics.Contraindications to study drugs.Baseline CharacteristicsGroups were well-matched at baseline.Cardiothoracic ratio: Slightly higher in prazosin group.Exercise tolerance: Slightly lower in prazosin group.InterventionsRandomized to receive additional treatment with placebo, prazosin, or the combination of hydralazine and isosorbide dinitrate.Stratified by presence of coronary artery disease.Initial dosage increased after two weeks unless side effects occurred.OutcomesPrimary OutcomesLower mortality at 2 years in hydralazine and isosorbide dinitrate group compared to placebo (risk reduction by 34%, P<0.028).Secondary OutcomesEjection fraction increased at 8 weeks and 1 year in hydralazine and isosorbide dinitrate group.Prazosin group had no significant improvement in mortality or left ventricular ejection fraction.CriticismsSmall sample size.Prazosin showed no significant benefit.FundingVeterans Administration Cooperative Studies Program.Further ReadingDetailed results and additional analysis of symptoms and exercise tolerance will inform the full impact of vasodilator therapy on chronic congestive heart failure.