Combination of isosorbide dinitrate and hydralazine in blacks with heart failure

N Engl J Med. 2004 Nov 11;351(20):2049-57. doi: 10.1056/NEJMoa042934. Epub 2004 Nov 8.

Abstract

Background: We examined whether a fixed dose of both isosorbide dinitrate and hydralazine provides additional benefit in blacks with advanced heart failure, a subgroup previously noted to have a favorable response to this therapy.

Methods: A total of 1050 black patients who had New York Heart Association class III or IV heart failure with dilated ventricles were randomly assigned to receive a fixed dose of isosorbide dinitrate plus hydralazine or placebo in addition to standard therapy for heart failure. The primary end point was a composite score made up of weighted values for death from any cause, a first hospitalization for heart failure, and change in the quality of life.

Results: The study was terminated early owing to a significantly higher mortality rate in the placebo group than in the group given isosorbide dinitrate plus hydralazine (10.2 percent vs. 6.2 percent, P=0.02). The mean primary composite score was significantly better in the group given isosorbide dinitrate plus hydralazine than in the placebo group (-0.1+/-1.9 vs. -0.5+/-2.0, P=0.01; range of possible values, -6 to +2), as were its individual components (43 percent reduction in the rate of death from any cause [hazard ratio, 0.57; P=0.01] 33 percent relative reduction in the rate of first hospitalization for heart failure [16.4 percent vs. 22.4 percent, P=0.001], and an improvement in the quality of life [change in score, -5.6+/-20.6 vs. -2.7+/-21.2, with lower scores indicating better quality of life; P=0.02; range of possible values, 0 to 105]).

Conclusions: The addition of a fixed dose of isosorbide dinitrate plus hydralazine to standard therapy for heart failure including neurohormonal blockers is efficacious and increases survival among black patients with advanced heart failure.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • African Continental Ancestry Group*
  • Aged
  • Double-Blind Method
  • Drug Combinations
  • Drug Therapy, Combination
  • Female
  • Heart Failure / drug therapy*
  • Heart Failure / ethnology*
  • Heart Failure / mortality
  • Humans
  • Hydralazine / adverse effects
  • Hydralazine / therapeutic use*
  • Isosorbide Dinitrate / adverse effects
  • Isosorbide Dinitrate / therapeutic use*
  • Male
  • Middle Aged
  • Nitric Oxide Donors / adverse effects
  • Nitric Oxide Donors / therapeutic use*
  • Quality of Life
  • Survival Analysis
  • Treatment Outcome
  • Vasodilator Agents / adverse effects
  • Vasodilator Agents / therapeutic use*

Substances

  • Drug Combinations
  • Nitric Oxide Donors
  • Vasodilator Agents
  • Hydralazine
  • Isosorbide Dinitrate