Objectives: Previous trials testing isosorbide dinitrate/hydralazine (I/H) were performed in all-male study cohorts, and thus the efficacy of I/H in women was unknown; 40% of the A-HeFT (African-American Heart Failure Trial) cohort were women. We therefore compared outcomes by gender and treatment. Background: Fixed-dose combined I/H significantly reduced mortality and heart failure hospitalizations and improved quality of life in 1,050 black patients with heart failure treated with background neurohormonal blockade. Previous trials testing I/H were done in all-male study cohorts, and thus the efficacy of I/H in women was unknown. Methods: Baseline characteristics and medications were compared between men and women by I/H and placebo treatment. Survival, time to first heart failure hospitalization, change in quality of life, and event-free survival were compared by gender and treatment. Results: At baseline, women had lower hemoglobin and creatinine levels; less renal insufficiency; and higher body mass indexes, diabetes prevalence, and systolic blood pressures; but worse quality of life scores. All-cause mortality was lower in women than in men treated with I/H but without significant treatment interaction by gender. The primary composite score, which weighted mortality, first heart failure hospitalization, and change in quality of life at 6 months, was similarly improved by I/H in men and women. First heart failure hospitalization and event-free survival (time to death or first heart failure hospitalization) were similarly improved in both genders. Conclusions: Fixed-dose I/H improved heart failure outcomes in both men and women in A-HeFT. The I/H significantly improved the primary composite score and event-free survival as well as reduced the risk of first heart failure hospitalizations similarly in both genders. The I/H had a slightly greater mortality benefit in women, but without a significant treatment interaction by gender.
Bibliographical noteFunding Information:
This study was sponsored by NitroMed, Inc. (Lexington, Massachusetts).