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