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

Research output: Contribution to journalArticle

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Abstract

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)
JournalCirculation
Volume87
Issue number6 SUPPL. 1
StatePublished - Jun 1993

Fingerprint

Isosorbide Dinitrate
Hydralazine
Exercise Tolerance
Enalapril
Heart Failure
Placebos
Prazosin
Exercise
Gases
Anaerobic Threshold
Exercise Therapy
Mortality
Digitalis
Enzyme Inhibitors
Therapeutics
Vasodilator Agents
Diuretics
isosorbide-hydralazine combination

Keywords

  • Anaerobic threshold
  • Enalapril
  • Oxygen consumption

Cite this

Hydralazine and isosorbide dinitrate combination improves exercise tolerance in heart failure : Results from V-HeFT I and V-HeFT II. / Ziesche, Susan; Cobb, Frederick R.; Cohn, Jay N.; Johnson, Gary; Tristani, Felix.

In: Circulation, Vol. 87, No. 6 SUPPL. 1, 06.1993.

Research output: Contribution to journalArticle

Ziesche, Susan ; Cobb, Frederick R. ; Cohn, Jay N. ; Johnson, Gary ; Tristani, Felix. / Hydralazine and isosorbide dinitrate combination improves exercise tolerance in heart failure : Results from V-HeFT I and V-HeFT II. In: Circulation. 1993 ; Vol. 87, No. 6 SUPPL. 1.
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abstract = "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.",
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N2 - 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.

AB - 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.

KW - Anaerobic threshold

KW - Enalapril

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