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


Therapeutics

Amiodarone decreased mortality in patients with ventricular arrhythmias after myocardial infarction

ACP J Club. 1993 July-Aug;119:1. doi:10.7326/ACPJC-1993-119-1-001


Source Citation

Pfisterer ME, Kiowski W, Brunner H, Burckhardt D, Burkart F. Long-term benefit of 1-year amiodarone treatment for persistent complex ventricular arrhythmias after myocardial infarction. Circulation. 1993 Feb;87:309-11.


Abstract

Objective

To study the long-term mortality for patients who received amiodarone for 1 year for asymptomatic complex ventricular arrhythmias after a myocardial infarction (MI).

Design

Randomized controlled trial with mean follow-up of 72 months.

Setting

A university and 2 affiliated hospitals in Switzerland.

Patients

212 patients who had survived MI and had asymptomatic complex ventricular arrhythmias for ≥ 2 weeks. Follow-up was 96% for mortality.

Intervention

98 patients were allocated to low-dose amiodarone, 200 mg/d for 5 days, after a loading dose of 1000 mg. 114 patients were allocated to receive no arrhythmia medication. 100 patients were allocated to individualized antiarrhythmic treatment and were not included in the analysis. After 1 year amiodarone was discontinued, and all patients received arrhythmia medication at the discretion of their physicians.

Main outcome measures

Mortality and cardiac mortality ascertained from telephone interviews, hospital records, and death certificates. Holter monitoring measured severity of arrhythmias.

Main results

After amiodarone was discontinued, patients who had taken the drug had an increase in Lown class III and IV ventricular ectopic activity (P < 0.05 for both). Fewer patients who took amiodarone died during follow-up compared with control-group patients { P = 0.02}* (Table). Using Kaplan-Meier actuarial life-table analysis, the probability of death after 84 months was 30% for patients who took amiodarone and 45% for control-group patients (P = 0.024). The amiodarone group had a lower overall total mortality (P = 0.03) and a lower overall cardiac mortality (P = 0.047). Both of these were caused by lower mortality in the first year of the study. The groups did not differ for deaths that occurred after discontinuation of amiodarone after 1 year.

Conclusion

Amiodarone, given for 1 year to patients with persistent complex ventricular arrhythmias after myocardial infarction, decreased mortality. This decrease in mortality was present 6 years after amiodarone had been discontinued.

* P value calculated from data in article.

Source of funding: Swiss National Foundation for Scientific Research.

For article reprint: Dr. M.E. Pfisterer, Division of Cardiology, Department of Internal Medicine, University Hospital Clinics, CH-4031 Basel, Switzerland. FAX 41-61-265-4598.


Table. Amiodarone vs control after mean follow-up of 72 months in patients with asymptomatic complex ventricular arrhythmias after a myocardial infarction†

Outcome Amiodarone Control RRR (95% CI) NNT (CI)
Deaths 33% 49% 32% (5 to 52) 7 (4 to 49)

†Abbreviations defined in Glossary; RRR, NNT, and CI calculated from data in article.


Commentary

The study by Pfisterer and colleagues provides long-term follow-up from the original BASIS (Basel Antiarrhythmic Study of Infarct Survivors) study, which suggested that amiodarone lowers mortality after an MI. The study adds to a meta-analysis, which showed an odds ratio of 0.66 (CI 0.47 to 0.93) in treatment compared with control groups when 1293 patients from BASIS and 6 other trials were combined (1). In several years, results are also expected from 2 large-scale trials under way—1 from Canada (1200 patients planned) and the other from Europe (1500 patients).

Since publication of the Pfisterer study, several additional trials with amiodarone have been published (3-5) and reviewed in ACP Journal Club (6). In addition, 2 systematic reviews have been published (7, 8). Taken together, these data would suggest that amiodarone lacks the adverse experience of class I and other class III anti-arrhythmic drugs when used for secondary prevention after MI. However, reduction in mortality and sudden death is not consistent, and the universal application of amiodarone to survivors of MI, even when left ventricular function is depressed, is not warranted. Implanted defibrillators have been shown to have an expanding role when arrhythmias are established after MI (9), and may be superior to amiodarone in such patients.

Steven Borzak, MD
Henry Ford HospitalDetroit, Michigan, USA


References

1. Teo K, Yusuf S, Furburg C. Overview of randomized trials of low-dose amiodarone on mortality in cardiac patients [Abstract]. Circulation. 1992;86(Suppl 1): I-534.

2. Cairns JA, Connolly SJ, Roberts R, Gent M. Amiodarone for patients with ventricular premature depolarizations after myocardial infarction: is it safe to stop treatment after one year? [Editorial]. Circulation. 993;87:637-9.

3. Julian DG, Camm AJ, Frangin G, et al., for the European Myocardial Infarct Amiodarone Trial Investigators. Randomised trial of effect of amiodarone on mortality in patients with left-ventricular dysfunction after recent myocardial infarction: EMIAT. Lancet. 1997;346:667-74.

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5. Singh SN, Fletcher RD, Fisher SG, et al. Amiodarone in patients with congestive heart failure and asymptomatic ventricular arrhythmia. Survival Trial of Antiarrhythmic Therapy in Congestive Heart Failure. N Engl J Med. 1995;333:77-82.

6. Bates ER. Commentary on “Effect of amiodarone on mortality after myodardial infarction.” ACP J Club. 1993 May-Jun:74 (Ann Intern Med. vol 120, suppl 3). Comment on: Ceremuzynski L, Kleczar E, Krzeminska-Pabula M, et al. Effect of amiodarone on mortality after myocardial infarction: a double-blind, placebo-controlled pilot study. J Am Coll Cardiol. 1992;20:1056-62.

7. Sim I, McDonald KM, Lavori PW, Norbutas CM, Hlatky MA. Quantitative overview of randomized trials of amiodarone to prevent sudden cardiac death. Circulation. 1997;96:2823-9.

8. Amiodarone Trials Meta-Aanlysis Investigators. Effect of prophylactic amiodarone on mortality after acute myocardial infarction and in congestive heart failure: meta-analysis of individual data from 6500 patients in randomised trials. Lancet. 1997;350:1417-24.

9. Moss AJ, Hall WJ, Cannom DS, et al., for the Multicenter Automatic Defibrillator Implantation Trial Investigators. Improved survival with an implanted defibrillator in patients with coronary disease at high risk for ventricular arrhythmia. N Engl J Med. 1996;335:1933-40.