Elsevier

The Lancet

Volume 349, Issue 9053, 8 March 1997, Pages 675-682
The Lancet

Articles
Randomised trial of outcome after myocardial infarction in patients with frequent or repetitive ventricular premature depolarisations: CAMIAT*

https://doi.org/10.1016/S0140-6736(96)08171-8Get rights and content

Summary

Background

Survivors of acute myocardial infarction with frequent or repetitive ventricular premature depolarisations (VPDs) have higher mortality 1–2 years after the event than those without VPDs. Although there is no therapy of proven efficacy for such patients, previous studies of amiodarone have been encouraging. CAMIAT was a randomised double-blind placebo-controlled trial designed to assess the effect of amiodarone on the risk of resuscitated ventricular fibrillation or arrhythmic death among survivors of myocardial infarction with frequent or repetitive VPDs (≥10 VPDs per h or ≥1 run of ventricular tachycardia).

Methods

Patients from 36 Canadian hospitals were randomly assigned amiodarone or placebo; a loading dose of 10 mg/kg daily for 2 weeks, a maintenance dose of 300–400 mg daily for 3·5 months, 200–300 mg daily for 4 months, and 200 mg for 5–7 days per week for 16 months. Patients were followed up for 2 years. The primary outcome was the composite of resuscitated ventricular fibrillation or arrhythmic death.

Findings

We recruited 1202 patients (606 in the amiodarone group and 596 in the placebo group). The mean follow-up was 1·79 years (SD 0·44). In the efficacy analysis, resuscitated ventricular fibrillation or arrhythmic death occurred in 31 (6·0%) patients in the placebo group and in 15 (3·3%) in the amiodarone group (relative-risk reduction 48·5% [95% CI 4·5 to 72·2], p=0·016). In the intention-to-treat analysis, primary outcome events occurred in 24 (6·9%) patients in the placebo group and in 15 (4·5%) in the amiodarone group (38·2% [95% CI −2·1 to 62·6], p=0·029). The absolute-risk reductions were greatest among patients with congestive heart failure or a history of myocardial infarction.

Interpretation

Amiodarone reduces the incidence of ventricular fibrillation or arrhythmic death among survivors of acute myocardial infarction with frequent or repetitive VPDs. Treatment decisions for individual survivors should require an assessment of their baseline risk factors and judgments based on the synthesis of our findings with those of related trials.

Introduction

Patients who survive the acute phase of myocardial infarction have a mortality rate of about 10% during the subsequent year. This mortality rate has changed little during the past 20 years, whereas a substantial decrease in mortality among hospital inpatients has occurred since the advent of thrombolytic therapy.1 The main predictors of late mortality after acute myocardial infarction are left-ventricular dysfunction, ventricular arrhythmias, residual ischaemia, and age.1, 2, 3, 4, 5 A substantial proportion of late deaths among survivors of myocardial infarction result from ventricular fibrillation, and several clinical trials of antiarrhythmic drugs have been conducted in an attempt to reduce this mortality. Six randomised controlled trials of long-term antiarrhythmic therapy were reported before 1981, but none showed any benefit from such therapy.6 However, small sample size, failure to select high-risk patients, and the use of drugs with low antiarrhythmic potency were thought to have contributed to this lack of therapeutic benefit. The Cardiac Arrhythmia Suppression Trial was designed to overcome these deficiencies, but had to be stopped early because of excess mortality among patients who received flecainide, encainide, and moricizine.7, 8 An overview of mortality data from 138 trials of antiarrhythmic drugs showed a significant excess mortality among survivors of myocardial infarction who received class I drugs.9

Amiodarone, an iodine-containing benzofuran originally classified as a class III antiarrhythmic agent with minor class-II effects, and later recognised to also have class-I and class-IV effects, is widely used for the prevention of sustained ventricular tachycardia and fibrillation.10 However, concerns about potentially dangerous non-cardiac side-effects and the complex pharmacokinetics have, until recently, limited the use of amiodarone to the most drug-resistant and high-risk patients. In the Basel Antiarrhythmic Study of Infarct Survival,11 amiodarone significantly reduced all-cause mortality among survivors of myocardial infarction who had frequent or repetitive ventricular premature depolarisations (VPDs). In the Polish Amiodarone Study,12 the drug significantly reduced cardiac mortality among survivors of myocardial infarction who were not eligible for β-blocker therapy. The Canadian Amiodarone Myocardial Infarction Arrhythmia Trial (CAMIAT) Pilot Study13 reported substantial suppression of VPDs, little amiodarone toxicity, and a favourable trend for the reduction of all-cause mortality. An overview of eight published trials of amiodarone in survivors of myocardial infarction reported an odds ratio of mortality for amiodarone versus control of 0·71 (95% CI 0·51–0·97; p=0·03).9

Among survivors of acute myocardial infarction with at least 10 VPDs per h, substantial, independent increases in mortality risk have been reported in previous studies, whether or not patients received a thrombolytic agent. The prevalence of these predictive arrhythmias was about 20%.3, 5 Thus, we had a strong rationale for conducting our study of amiodarone for the reduction of mortality among survivors of myocardial infarction with frequent or repetitive VPDs.

Section snippets

Eligibility of patients

Details of the protocol have been published previously.14 The study was conducted in 36 acute-care hospitals throughout Canada between June, 1990, and November, 1995. To be eligible patients had to be older than 19 years and have had acute myocardial infarction within the previous 6–45 days, based on the presence of two of three criteria—characteristic ischaemic pain in the precordium or associated referral areas for at least 20 min during physical and emotional rest; activities of creatine

Results

The trial profile shows overall patient numbers throughout the study (figure 1). 1202 patient were enrolled between June, 1990, and November, 1994 (606 in the amiodarone group, 596 in the placebo group). Screening logs were not maintained throughout the trial but we used data from intermittent surveys to calculate that about 4800 (20%) of myocardial infarction survivors met the ambulatory ECG monitoring entry criteria. We estimated that 2400 of these survivors met all other eligibility

Discussion

The mortality rate among hospital inpatients with myocardial infarction has fallen sharply in the past few years, whereas that among survivors of myocardial infarction over the ensuing 1–2 years has not fallen appreciably.1 Frequent or repetitive VPDs on ambulatory monitoring are an independent predictor of outcome and are found in more than 20% of patients who have received thrombolytic therapy.5 This trial showed that among survivors of myocardial infarction with frequent or repetitive VPDs

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