A Comparison of Enalapril with Hydralazine Isosorbide Dinitrate in the Treatment of Chronic Congestive Heart failure - VHEFT-II


Enalapril vs. hydralazine/nitrates for mortality in moderate heart failure.


Enalapril will reduce mortality more than the combination of hydralazine-isosorbide dinitrate in patients with moderately severe congestive heart failure.

Study Design

Study Design:

Patients Screened: 2,741
Patients Enrolled: 804
NYHA Class: I=(6%), II=(51%),III=(43%)
Mean Follow Up: 2.5 years (6 months - 5.7 years)
Mean Patient Age: 60
Female: 0
Mean Ejection Fraction: 29%

Patient Populations:

Men ages 18-75 (chronic heart failure)
Evidence of cardiac dysfunction - CT ratio > 0.55, left ventricular dimension > 2.7 cm/sqm BSA, or EF < 45% in association with reduced exercise tolerance


MI or cardiac surgery in prior 3 months
Angina limiting exercise
Obstructive valvular disease
Obstructive pulmonary disease

Primary Endpoints:

Overall 2 year mortality

Secondary Endpoints:

Ejection fraction
Exercise capacity (peak oxygen consumption)
Clinical assessment
Plasma norepinephrine

Drug/Procedures Used:

Enalapril (20 mg/day)
Hydralazine/Isosorbide dinitrate (300/160 mg)

Concomitant Medications:

Nitroglycerin (16%)
Antiarrhythmics (25%)
Anticoagulants (21%)
Digoxin (100%)
Diuretics (100%)

Principal Findings:

Two year mortality significantly lower in Enalapril group (18% versus 25%; p = 0.016)

Overall mortality also lower with Enalapril but did not reach statistical significance for duration of follow-up (p = 0.08).

Lower mortality in Enalapril group due to lower incidence of sudden death.

Ejection fraction increased in both groups but was significantly greater in hydralazine/isosorbide dinitrate group.

Increased oxygen consumption in hydralazine/isosorbide dinitrate group at 13 weeks and 6 months; after one year, peak oxygen consumption declined in both groups.


Enalapril improved mortality more than hydralazine/isosorbide dinitrate in this study and had significant impact on exercise and LVEF. Survival curves of hydralazine/isosorbide dinitrate group from VHeFT I and II are almost identical. ACE inhibitors seem to improve outcome in congestive heart failure by different mechanisms than directly acting vasodilators.


1. N Engl J Med 1991;325:303-10. Final results

Keywords: Exercise Tolerance, Isosorbide Dinitrate, Drug Combinations, Enalapril, Follow-Up Studies, Hydralazine, Oxygen Consumption, Nitrates, Heart Failure, Death, Sudden, Cardiac, Vasodilator Agents

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