A comparison of enalapril with hydralazine–isosorbide dinitrate in the treatment of chronic congestive heart failure

Jay N Cohn, Gary Johnson, Susan Ziesche, Frederick Cobb, Gary S Francis, Felix Tristani, Raphael Smith, W. Bruce Dunkman, Henry Loeb, Maylene Wong, Geetha Bhat, Steven Goldman, Ross D. Fletcher, James Doherty, C. Vincent Hughes, Peter Carson, Guillermo Cintron, Ralph Shabetai, Clair Haakenson

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Abstract

Background and Methods. To define better the efficacy of vasodilator therapy in the treatment of chronic congestive heart failure, we compared the effects of hydralazine and isosorbide dinitrate with those of enalapril in 804 men receiving digoxin and diuretic therapy for heart failure. The patients were randomly assigned in a double-blind manner to receive 20 mg of enalapril daily or 300 mg of hydralazine plus 160 mg of isosorbide dinitrate daily. The latter regimen was identical to that used with a similar patient population in the effective-treatment arm of our previous Vasodilator—Heart Failure Trial. Results. Mortality after two years was significantly lower in the enalapril arm (18 percent) than in the hydralazine—isosorbide dinitrate arm (25 percent) (P = 0.016; reduction in mortality, 28.0 percent), and overall mortality tended to be lower (P = 0.08). The lower mortality in the enalapril arm was attributable to a reduction in the incidence of sudden death, and this beneficial effect was more prominent in patients with less severe symptoms (New York Heart Association class I or II). In contrast, body oxygen consumption at peak exercise was increased only by hydralazine—isosorbide dinitrate treatment (P<0.05), and left ventricular ejection fraction, which increased with both regimens during the 2 years after randomization, increased more (P<0.05) during the first 13 weeks in the hydralazine—isosorbide dinitrate group. Conclusions. The similar two-year mortality in the hydralazine—isosorbide dinitrate arms in our previous Vasodilator—Heart Failure Trial (26 percent) and in the present trial (25 percent), as compared with that in the placebo arm in the previous trial (34 percent), and the further survival benefit with enalapril in the present trial (18 percent) strengthen the conclusion that vasodilator therapy should be included in the standard treatment for heart failure. The different effects of the two regimens (enalapril and hydralazine—isosorbide dinitrate) on mortality and physiologic end points suggest that the profile of effects might be enhanced if the regimens were used in combination. (N Engl J Med 1991;325:303–10.).

Original languageEnglish (US)
Pages (from-to)303-310
Number of pages8
JournalNew England Journal of Medicine
Volume325
Issue number5
DOIs
StatePublished - Aug 1 1991

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Enalapril
Heart Failure
Mortality
Isosorbide Dinitrate
Hydralazine
Vasodilator Agents
Therapeutics
Digoxin
Random Allocation
Sudden Death
Treatment Failure
Diuretics
Oxygen Consumption
Stroke Volume
Placebos
Exercise
Survival
Incidence
Population

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A comparison of enalapril with hydralazine–isosorbide dinitrate in the treatment of chronic congestive heart failure. / Cohn, Jay N; Johnson, Gary; Ziesche, Susan; Cobb, Frederick; Francis, Gary S; Tristani, Felix; Smith, Raphael; Dunkman, W. Bruce; Loeb, Henry; Wong, Maylene; Bhat, Geetha; Goldman, Steven; Fletcher, Ross D.; Doherty, James; Hughes, C. Vincent; Carson, Peter; Cintron, Guillermo; Shabetai, Ralph; Haakenson, Clair.

In: New England Journal of Medicine, Vol. 325, No. 5, 01.08.1991, p. 303-310.

Research output: Contribution to journalArticle

Cohn, JN, Johnson, G, Ziesche, S, Cobb, F, Francis, GS, Tristani, F, Smith, R, Dunkman, WB, Loeb, H, Wong, M, Bhat, G, Goldman, S, Fletcher, RD, Doherty, J, Hughes, CV, Carson, P, Cintron, G, Shabetai, R & Haakenson, C 1991, 'A comparison of enalapril with hydralazine–isosorbide dinitrate in the treatment of chronic congestive heart failure', New England Journal of Medicine, vol. 325, no. 5, pp. 303-310. https://doi.org/10.1056/NEJM199108013250502
Cohn, Jay N ; Johnson, Gary ; Ziesche, Susan ; Cobb, Frederick ; Francis, Gary S ; Tristani, Felix ; Smith, Raphael ; Dunkman, W. Bruce ; Loeb, Henry ; Wong, Maylene ; Bhat, Geetha ; Goldman, Steven ; Fletcher, Ross D. ; Doherty, James ; Hughes, C. Vincent ; Carson, Peter ; Cintron, Guillermo ; Shabetai, Ralph ; Haakenson, Clair. / A comparison of enalapril with hydralazine–isosorbide dinitrate in the treatment of chronic congestive heart failure. In: New England Journal of Medicine. 1991 ; Vol. 325, No. 5. pp. 303-310.
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T1 - A comparison of enalapril with hydralazine–isosorbide dinitrate in the treatment of chronic congestive heart failure

AU - Cohn, Jay N

AU - Johnson, Gary

AU - Ziesche, Susan

AU - Cobb, Frederick

AU - Francis, Gary S

AU - Tristani, Felix

AU - Smith, Raphael

AU - Dunkman, W. Bruce

AU - Loeb, Henry

AU - Wong, Maylene

AU - Bhat, Geetha

AU - Goldman, Steven

AU - Fletcher, Ross D.

AU - Doherty, James

AU - Hughes, C. Vincent

AU - Carson, Peter

AU - Cintron, Guillermo

AU - Shabetai, Ralph

AU - Haakenson, Clair

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N2 - Background and Methods. To define better the efficacy of vasodilator therapy in the treatment of chronic congestive heart failure, we compared the effects of hydralazine and isosorbide dinitrate with those of enalapril in 804 men receiving digoxin and diuretic therapy for heart failure. The patients were randomly assigned in a double-blind manner to receive 20 mg of enalapril daily or 300 mg of hydralazine plus 160 mg of isosorbide dinitrate daily. The latter regimen was identical to that used with a similar patient population in the effective-treatment arm of our previous Vasodilator—Heart Failure Trial. Results. Mortality after two years was significantly lower in the enalapril arm (18 percent) than in the hydralazine—isosorbide dinitrate arm (25 percent) (P = 0.016; reduction in mortality, 28.0 percent), and overall mortality tended to be lower (P = 0.08). The lower mortality in the enalapril arm was attributable to a reduction in the incidence of sudden death, and this beneficial effect was more prominent in patients with less severe symptoms (New York Heart Association class I or II). In contrast, body oxygen consumption at peak exercise was increased only by hydralazine—isosorbide dinitrate treatment (P<0.05), and left ventricular ejection fraction, which increased with both regimens during the 2 years after randomization, increased more (P<0.05) during the first 13 weeks in the hydralazine—isosorbide dinitrate group. Conclusions. The similar two-year mortality in the hydralazine—isosorbide dinitrate arms in our previous Vasodilator—Heart Failure Trial (26 percent) and in the present trial (25 percent), as compared with that in the placebo arm in the previous trial (34 percent), and the further survival benefit with enalapril in the present trial (18 percent) strengthen the conclusion that vasodilator therapy should be included in the standard treatment for heart failure. The different effects of the two regimens (enalapril and hydralazine—isosorbide dinitrate) on mortality and physiologic end points suggest that the profile of effects might be enhanced if the regimens were used in combination. (N Engl J Med 1991;325:303–10.).

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