A comparison of enalapril with hydralazine-isosorbide dinitrate in the treatment of chronic congestive heart failure
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| A Comparison of Enalapril With Hydralazine-Isosorbide Dinitrate in the Treatment of Chronic Congestive Heart Failure (VHeft II) | |||
| Authors | Cohn JN, Johnson G, Ziesche S, Cobb F, Francis G, et al. | ||
| Journal | New England Journal of Medicine | ||
| Year/Volume(Issue)/Pages | 1991;325(5):303-310 | ||
| Original Article Abstract | |||
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Contents |
Quick Summary
- The object of this study was to determine the efficacy of vasodilator therapy (enalapril versus hydralazine and isosorbide dinitrate) in the treatment of chronic congestive heart failure.
- Patients who were already recieving digoxin and diuretic therapy for heart failure where given either 20mg of enalapril daily or 300mg hydralazine plus 160mg of isosorbide dinitrate daily.
- It was concluded that vasodilator therapy is effective and should be included in the standard treatment for heart failure.
- Authors suggest that a combination of enalapril and isosorbide dinitrate may provide enhanced protection due to different effects of the two regimens.
Hypothesis/Objectives
The first five-year, multicenter Veterans Administration Cooperative Vasodilator-Heart Failure trial (V-HeFT I) showed hydralazine and isosorbide dinitrate to be effective in reducing mortality in patients with mild-to-moderate heart failure. The Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS) trial showed enalapril to be effective in treating patients with severe heart disease. This trial aimed to study the efficacy of enalapril versus hyralazine and isosorbide dinitrate in mild-to-moderate heart failure.
Methods/Design
| Y | Randomized? | ||
| Y | Controlled? | ||
| N | Placebo-controlled? | ||
| Y | Prospective? | ||
| U | Double-blind? | ||
| *U = not reported | |||
Inclusion criteria
- Based on evidence of cardiac dysfunction in association with reduced exercise tolerance:
- Cardiothoracic ratio (>/= 0.55) on chest radiography
- Left ventricular internal diameter >2.7cm per square meter of body-surface area at distole on echocardiography
- Ejection fraction less than 0.45 as determined with radionuclide methods
Exclusion criteria
- Myocardial infarction or cardiac surgery within the previous three months.
- Angina pectoris limiting exercise or requiring long-term medical therapy.
- Serious obstructive valvular disease.
- Obstructive lung disease (ratio of forced expiratory volume in one second to forced vital capacity, <0.60).
- Other diseases likely to limit life expectancy.
Design
Each patient received three bottles of medication: either a bottle of enalapril and two bottles of placebo or a bottle of hydralazine, a bottle of isosorbide dinitrate, and a bottle of placebo. Every patient recieved the same directions for the three medications for two weeks and then they were titrated to the full daily treatment of either 20mg enalapril or 300mg hydralazine plus 160mg isosorbide mononitrate. Follow-up visits with clinical and laboratory evaluations were scheduled at three-month intervals after the titration of initial dose. Excercise testing with gas-exchange measurements were done at 13weeks and at 6-month intervals. Chest radiography to determine cardiothoracic ratios and radionuclide measurements of ejection fractions were done yearly. Quality of life questionnaires were done every six months.
Results
Baseline characteristics
804 patients were enrolled in the trial and randomly assigned to enalapril (403 patients) or hydralazine-isosorbide dinitrate (401 patients). The were no significant differences in baseline characteristics between the two groups.
Primary endpoint results
Two years after the initiation of randomized therapy, mortality in the enalapril group was significantly lower than in the hydralazine-isosorbide dinitrate group (P=0.016 by a two-tailed test). The reduction in mortality in the enalapril group was 33.6% after one year, 28.2% after two years, 14.0% after three years, 10.3% after four years, and 11.1% at the end of the follow up period. Patients with less severe symptoms of heart failure and without coronary disease had more beneficial results on mortality than others.
Other
Blood pressure was reduced during follow-up in both treatment groups, but the reduction in systolic pressure (by 5 mmHg) and diastolic pressure (by 4 mmHg) with enalapril was significantly more than with hydralazine-isosorbide dinitrate ( by 0 mmHg systolic and 1 mmHg diastolic). Hyralazine-isosorbide dinitrate produced significantly more improvement in exercise performance and left ventricular function. There was no significant difference in the number of patients hospitalized in the two groups.
Limitations
- This trial was an extension of V-HeFT I so there was no placebo group in this study.
- Based on results from V-HeFT I hydralazine-isosorbide dinitrate served as control group.
