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


Therapeutics

Congestive heart failure from dilitiazem after myocardial infarction

ACP J Club. 1991 May-Jun;114:65. doi:10.7326/ACPJC-1991-114-3-065


Source Citation

Goldstein RE, Boccuzzi SJ, Cruess D, Nattel S. Diltiazem increases late-onset congestive heart failure in postinfarction patients with early reduction in ejection fraction. Circulation. 1991;83:52-60. [PubMed ID: 1984898]


Abstract

Objective

To evaluate the influence of diltiazem on the occurrence of new or worsened congestive heart failure in patients defined by left ventricular function after myocardial infarction (MI).

Design

Secondary analysis of a randomized, double-blind, placebo-controlled trial with a mean follow-up of 25 months (range, 12 to 52 months).

Setting

38 hospitals in North America.

Patients

Patients with documented acute MI were enrolled. Patients were excluded if they had symptomatic hypotension, bradycardia, or complicating diseases. 2466 patients were randomized.

Intervention

Patients were assigned to diltiazem, 240 mg/d, or placebo 3 to 15 days after acute MI.

Main outcome measure

New or worsened congestive heart failure was judged clinically, based on symptoms or signs of left ventricular dysfunction, such as orthopnea or bibasilar pulmonary rales.

Main results

Diltiazem increased the occurrence of late congestive heart failure more than did placebo in patients with anterolateral Q-wave infarction (P = 0.04) (Table). Diltiazem also increased the occurrence of late congestive heart failure more than did placebo in patients with an ejection fraction < 0.40 (P = 0.004) (Table). The association between diltiazem treatment and increased occurrence of late congestive heart failure in patients with reduced ejection fraction was substantiated by life-table analysis (P = 0.002). This effect was evident among patients with reduced ejection fraction who did not receive β-blockers (P = 0.008) but not in those who did receive β-blockers. (P = 0.22). The diltiazem-asso- ciated increase in late congestive heart failure was progressively larger as baseline ejection fraction was reduced.

Conclusion

Patients with an ejection fraction < 0.40 who have had an acute myocardial infarction have an increased risk for congestive heart failure when treated with diltiazem.

Source of funding: In part, Marion Laboratories.

Address for article reprint: Dr. R.E. Goldstein, Room A-3060, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814-4799, USA.


Table. Diltiazem vs placebo in postinfarction patient subgroups on late congestive heart failure at mean follow-up of 25 mo*

Patients Diltiazem Placebo RRI (95%CI) NNH (CI)
With anterolateral Q-wave infarction 13% 9% 53% (2 to 129) 22 (11 to 508)
With ejection fraction <0.40 21% 12% 723% (19 to 148) 12 (7 to 35)

*Abbreviations defined in Glossary; RRI, NNH, and CI calculated from data in article.


Commentary

This reanalysis of the Multicenter Diltiazem Postinfarction Trial (MDPIT) adds to a growing body of evidence that suggests calcium antagonists are deleterious for patients with left ventricular dysfunction (1, 2). These particular results, however, must be interpreted cautiously. They stem from a secondary data analysis that lacked a standard method for diagnosing the end point of congestive heart failure. More than half of the patients studied had their baseline left ventricular function determined after receiving placebo or diltiazem for a few days. Although covariates, such as known β-blocker use at baseline, were examined, effects of co-interventions during study follow-up were not assessed. Despite these limitations, these carefully analyzed findings from a large, randomized, double-blind, placebo-controlled trial should steer clinicians away from using diltiazem in postinfarction patients with impaired left ventricular function.

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


References

1. Agostoni PC, DeCesare N, Doria E, et al. Afterload reduction: a comparison of captopril and nifedipine in dilated cardiomyopathy. Br Heart J. 1986;55:391-9.

2. Packer M, Kessler PD, Lee WH. Calcium-channel blockade in the management of severe chronic congestive heart failure: a bridge too far. Circulation. 1987;75(Suppl V): V-56-64.


Author's Response

My co-authors and I appreciate Dr. Mulrow's positive comments. We emphasize that timing of functional assessment (before or after initiation of study drug) and use of β-blockers appeared to make little difference in our results. Diltiazem use in patients with reduced left ventricular ejection fraction was associated with increased late congestive heart failure in each subgroup. An extensive list of covariates failed to identify imbalances that could explain our data. Readers should also consider the outcome of the primary MDPIT analysis: Diltiazem use in postinfarction patients with impaired left ventricular function was associated with substantially more cardiac events (cardiac death or nonfatal reinfarction) during follow-up (1). Thus, our results confirm and reinforce recommendations developed in the primary analysis: Diltiazem should be avoided in postinfarction patients with impaired left ventricular function.

Robert E. Goldstein, MD

1. The Multicenter Diltiazem Postinfarction Trial Research Group. The effect of diltiazem on mortality and reinfarction after myocardial infarction. N Engl J Med. 1988;319:385-92.