Hydralazine and isosorbide dinitrate combination improves exercise tolerance in heart failure: Results from V-HeFT I and V-HeFT II

Susan Ziesche, Frederick R. Cobb, Jay N. Cohn, Gary Johnson, Felix Tristani

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86 Scopus citations


Background. To better define the effects of long-term vasodilator therapy on exercise performance in chronic congestive heart failure, we compared placebo with prazosin and with the combination of hydralazine and isosorbide dinitrate (Hyd-Iso) in 642 men over a 5-year period in V-HeFT I. Methods and Results. Patients were randomized (double-blind) to 20 mg of prazosin daily or 300 mg of hydralazine plus 160 mg daily of isosorbide dinitrate or placebo. We compared enalapril (20 mg daily), a converting enzyme inhibitor, with Hyd-Iso in 804 men over another 5-year period in V-HeFT II. Background therapy in both trials consisted of digitalis and diuretics. Serial bicycle ergometric exercise was performed with gas exchange measurements during progressive incremental work rates to a symptom-limited peak end point. Gas exchange anaerobic threshold (ATge) measurement was performed in the second trial. In V-HeFT I, an increase in peak V̇o2 with Hyd-Iso compared with placebo approached significance at 2 months (p<0.16) and was significant (p<0.04) at 1 year. In V-HeFT II, Hyd-Iso significantly increased peak Vo2 compared with enalapril (p<0.01 at 3 months, p<0.02 at 6 months and 2 years). The changes in ATge measurements were not statistically different between the two treatment groups in V-HeFT II. Conclusions. Combination therapy with Hyd-Iso was more effective in increasing peak V̇o2 than placebo, prazosin, or enalapril in patients with mild-to-moderate congestive heart failure. Long-term data were confounded by mortality and other events, which may have led to an underestimate of the benefits of Hyd-Iso over placebo and an underestimate of the long-term benefits of enalapril on exercise performance. Therefore, short-term improvement in exercise performance is a suitable therapeutic end point, but long-term studies should more appropriately assess mortality.

Original languageEnglish (US)
Pages (from-to)VI56-VI64
Issue number6 SUPPL. 1
StatePublished - Jun 1993


  • Anaerobic threshold
  • Enalapril
  • Oxygen consumption


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