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


Therapeutics

Captopril reduced the progression of mild congestive heart failure but did not reduce mortality

ACP J Club. 1992 Sept-Oct;117:41. doi:10.7326/ACPJC-1992-117-2-041


Source Citation

Kleber FX, Niemöller L, Doering W. Impact of converting enzyme inhibition on progression of chronic heart failure: results of the Munich Mild Heart Failure Trial. Br Heart J. 1992 Apr;67:289-96.


Abstract

Objective

To delay progression of mild-to-moderate congestive heart failure by adding captopril to an optimally adjusted standard treatment regimen.

Design

Randomized, double-blind, placebo-controlled trial with patients stratified for duration of congestive heart failure.

Setting

Cardiology department in a university-affiliated German hospital.

Patients

170 patients (mean age, 62 y; 128 men) with congestive heart failure (New York Heart Association [NYHA] classes I to III, confirmed by the modified Framingham criteria) were randomized. 72% of patients were in NYHA classes I and II. 69% had had a previous myocardial infarction. Patients with severe heart failure (NYHA class IV), valvular heart disease, or other conditions greatly affecting prognosis were excluded. 37 patients (22%) were withdrawn, but all patients were followed (median 2.7 y) and included in the intention-to-treat analysis.

Intervention

83 patients were randomized to captopril, 6.25 mg increasing to 25 mg, twice a day, with maximum dosage reduced when serum creatinine was > 265 mmol/L. 87 patients were assigned to placebo. Treatment for congestive heart failure with any drug other than angiotensin-converting enzyme (ACE) inhibitors was allowed as needed. Captopril, 25 to 50 mg twice daily, was added to the regimen if heart failure progressed to NYHA class IV.

Main outcome measures

Death from heart failure (sudden death or pump failure death) and progression to NYHA class IV despite optimal standard treatment.

Main results

A trend was seen for fewer patients in the captopril group than in the placebo group to have died from progressive heart failure (pump failure) (4 patients [5%] vs 11 [13%] {95% CI for the difference of 8%, -0.5% to 16%}*, P = 0.1), and the groups did not differ in sudden death (captopril, 11 patients [13%] vs placebo, 10 [11%]) or in all-cause mortality (22 deaths in each group). Heart failure progressed to class IV in 9 patients (11%) assigned to captopril compared with 23 patients (26%) assigned to placebo (P = 0.01). {This absolute risk reduction of 15% means that 7 patients would need to be treated with captopril (rather than placebo) to prevent 1 additional patient from progressing to more severe congestive heart failure, CI 4 to 25; the relative risk reduction was 59%, CI 19% to 80%.}* The mean event-free time without death from heart failure or progression to NYHA class IV showed a progression (292 days longer) for patients in the captopril group (P = 0.07).

Conclusion

Captopril slowed the progression of mild-to-moderate congestive heart failure but did not reduce overall mortality.

Source of funding: In part, Squibb-von Heyden GmbH.

Address for article reprint: Dr. F.X. Kleber, Division of Cardiology, Munich Schwabing Hospital, Ludwig-Maximilians-University, Koelner Platz 1, D-8000 Munich 40, Germany.

*Numbers calculated from data in article.


Commentary

Two previous large trials documented improved survival with enalapril in patients with mild-to-moderate (1) and severe (2) heart failure. An additional trial showed enalapril was superior to nitrates plus hydralazine in reducing mortality (3). Improved survival in the former trials was attributed to decreased pump failure and, in the latter trial, to decreased sudden death. What does the study by Kleber and colleagues add to previous findings?

First, it confirms that ACE inhibitors are effective and should be given earlier rather than later to patients with mild-to-moderate heart failure. Second, it shows that captopril in relatively small doses is beneficial but does not address whether higher doses or treatment with enalapril might be more beneficial. Third, it adds to the evidence suggesting that major benefits of these agents in heart failure are attributable to reducing pump failure.

Limitations of this study include its small sample size compared with previous trials, a relatively high rate (29%) of withdrawals from captopril therapy, and a lack of precise description of co-intervention and crossovers from placebo to captopril during follow-up. Clinicians should be reminded, nonetheless, that ACE inhibitors have been proved effective in a broad spectrum of patients with symptomatic congestive heart failure. The relative merits of specific agents within this class as well as optimal doses of agents deserve further study.

Cynthia Mulrow, MD
Audie L. Murphy Memorial Veterans Administration HospitalSan Antonio, Texas, USA

Cynthia Mulrow, MD
Audie L. Murphy Memorial Veterans Administration Hospital
San Antonio, Texas, USA


References

1. 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.

2. The CONSENSUS Trial Study Group. Effects of enalapril on mortality in severe congestive heart failure: results of the Cooperative North Scandinavian Enalapril Survival Study. N Engl J Med. 1987;316:1429-35.

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