HYDRALAZINE AND ISOSORBIDE DINITRATE COMBINATION IMPROVES EXERCISE TOLERANCE IN HEART-FAILURE - RESULTS FROM V-HEFT-I AND V-HEFT-II

Background. To better define the effects of long-term vasodilator ther apy on exercise performance in chronic congestive heart failure, we co mpared placebo with prazosin and with the combination of hydralazine a nd 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 consist ed of digitalis and diuretics. Serial bicycle ergometric exercise was performed with gas exchange measurements during progressive incrementa l work rates to a symptom-limited peak end point. Gas exchange anaerob ic threshold (AT(ge)) measurement was performed in the second trial. I n 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 AT(ge) measurements were not statistically dif ferent between the two treatment groups in V-HeFT II. Conclusions. Com bination therapy with Hyd-Iso was more effective in increasing peak VO 2 than placebo, prazosin, or enalapril in patients with mild-to-modera te congestive heart failure. Long-term data were confounded by mortali ty and other events, which may have led to an underestimate of the ben efits of Hyd-Iso over placebo and an underestimate of the long-term be nefits of enalapril on exercise performance. Therefore, short-term imp rovement in exercise performance is a suitable therapeutic end point, but long-term studies should more appropriately assess mortality.