Hydralazine and isosorbide dinitrate combination improves exercise tolerance in heart failure. Results from V-HeFT I and V-HeFT II. The V-HeFT VA Cooperative Studies Group.
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.


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 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 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 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.
Ziesche
S
S
VA Medical Centers in Minneapolis, Minn.
Cobb
F R
FR
Cohn
J N
JN
Johnson
G
G
Tristani
F
F
D015308:Anaerobic Threshold / Q000502:physiology; D004359:Drug Therapy, Combination; D004656:Enalapril / Q000627:therapeutic use; D005080:Exercise Test; D017079:Exercise Tolerance / Q000187:drug effects*; D006333:Heart Failure / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D006830:Hydralazine / Q000627:therapeutic use*; D007548:Isosorbide Dinitrate / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011224:Prazosin / Q000627:therapeutic use
D006830:Hydralazine; D004656:Enalapril; D007548:Isosorbide Dinitrate; D011224:Prazosin