Current issues of ACP Journal Club are published in Annals of Internal Medicine


Enalapril saved more lives at minimal extra cost in congestive heart failure

ACP J Club. 1994 Nov-Dec;121:83. doi:10.7326/ACPJC-1994-121-3-083

Source Citation

Paul SD, Kuntz KM, Eagle KA, Weinstein MC. Costs and effectiveness of angiotensin converting enzyme inhibition in patients with congestive heart failure. Arch Intern Med. 1994 May 23;154:1143-9.



To determine the cost-effectiveness of adding either enalapril or the hydralazine-isosorbide combination to digoxin plus diuretic therapy in patients with congestive heart failure (CHF).


Decision analytic model to analyze the costs with efficacy data obtained from 3 randomized controlled trials, the Studies of Left Ventricular Dysfunction (SOLVD), and the Vasodilator Heart Failure Trials I and II.


Multicenter studies.


Patients with CHF and left ventricular ejection fractions ≤ 0.35.


Patients were assigned to standard therapy (digoxin and diuretic therapy plus no vasodilator agents) alone or with either a combination of hydralazine hydrochloride, 300 mg/d, and isosorbide dinitrate,160 mg/d, or enalapril, 20 mg/d.

Main cost and outcome measures

Effectiveness and costs were evaluated using a decision analytic model considering mortality and hospitalizations. Sensitivity analyses identified which variables (cost of drug, cost of hospitalization, efficacy of drug) were influential in determining incremental cost-effectiveness ratios. All costs are in 1992 US dollars.

Main results

In the base case analysis, the analysts assumed that treatment was continued for 10 years and that treatment efficacy lasted for 10 years. The model predicted that treating patients with hydralazine-isosorbide therapy would save an additional 8 days of life with a marginal cost of $119 (the overall cost of treating a patient with hydralazine-isosorbide therapy minus the costs averted by fewer hospitalizations compared with standard therapy), yielding an incremental cost-effectiveness ratio of $5600 per year of life saved. The additional cost of a patient treated with enalapril compared with the hydralazine-isosorbide combination was $2569 and the gain in life was 3 months, yielding an incremental cost-effectiveness ratio of $9700 per year of life saved. The results of the analysis were minimally sensitive to the duration of vasodilator efficacy, the effectiveness of treatment, or variations in risk reduction.


The gain in longevity per patient from enalapril relative to the hydralazine-isosorbide combination or no vasodilator therapy (3 months) was similar to gains from other widely used medications, whereas the additional cost per year of life saved (approximately $10 000) was relatively small compared with other commonly used treatments.

Source of funding: None.

For article reprint: Dr. S. D. Paul, Cardiac Unit, Massachusetts General Hospital, Ellison Room 908, Boston MA 02114, USA. FAX 617-724-4932.


Angiotensin-converting enzyme (ACE) inhibitors directly reduce vasoconstriction caused by angiotensin II. They also may inhibit degradation of the endogenous vasodilator bradykinin. These effects make ACE inhibitors valuable in treating CHF and hypertension and in slowing the decline of renal function in persons with diabetes . Several large trials have shown decreases in mortality among persons with CHF and improvement in their quality of life, with some studies using enalapril as the ACE inhibitor (1-3).

Paul and colleagues used decision analysis and economic models to show that enalapril therapy was more expensive but more effective than a hydralazine-isosorbide regimen. Because the study relied on data from randomized trials, its inferences are strong. Other researchers have reached similar conclusions (1).

Little reason exists to doubt that other ACE inhibitors would be similarly cost-effective. If the price of enalapril decreased or if other efficiencies were identified, the regimen might decrease costs in addition to prolonging life. The enhancement of the quality of life, at least for the first 2 to 3 years, makes this therapy even more attractive (1). This quality-of-life-enhancing effect has not been shown in patients with asymptomatic CHF, although the SOLVD study (3) did show a delay in the time to development of symptoms for patients taking enalapril.

John M. Eisenberg, MD
Georgetown UniversityWashington, D.C., USA


1. Wilde MI, Bryson HM, Goa KL. Enalapril. A review of quality-of-life and pharmacoeconomic aspects of its use in heart failure and mild to moderate hypertension. Pharmacoeconomics. 1994;6:155-82.

2. Cohn JN, Johnson G, Ziesche S, et al. A comparison of enalapril with hydralazine-isosorbide dinitrate in the treatment of chronic congestive failure. N Engl J Med. 1991;325:303-10.

3. The SOLVD Investigators. Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. N Engl J Med. 1991;325:293-302.