Hydralazine and Isosorbide Dinitrate Combination Improves Exercise Tolerance in Heart Failure Results from V-HeFT I and V-HeFT II

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

VA Medical Centers in Minneapolis, Minn., Durham, N.C., Milwaukee, Wis., and the Cooperative Studies Program Coordinating Center, VA Medical Center, West Haven, Conn.

Address for correspondence: Jay N. Cohn, MD, Cardiovascular Division, University of Minnesota Medical School, Box 488, 420 Delaware Street, S.E., Minneapolis, MN 55455-0392.

^*For a complete list of institutions and individuals participating in the V-HeFT VA Cooperative Studies, see the “Introduction” to this supplement.

Circulation 87(6):p VI-64, June 1993.

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 (AT,) measurement was performed in the second trial. In V-HeFT I, an increase in peak Vo₂ 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 ATg measurements were not statistically different between the two treatment groups in V-HeFIT II.

Conclusions

Combination therapy with Hyd-Iso was more effective in increasing peak Vo₂ 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.