Meta-analysis of antiarrhythmic drug trials

During the past 15 years, the efficacy of antiarrhythmic drugs has been investigated for reducing premature death in patients at high risk of arrhythmia. Whereas the benefits of beta-blocker therapy are well established, a reduction in mortality with other antiarrhythmic drugs remains unproved and in some cases, there is evidence of increased mortality with class I and some class III agents. A limitation of individual clinical trials is inadequate sample size to detect significant differences between interventions. Meta-analysis, by combining results from multiple clinical trials, provides a technique to overcome sample size limitations and assess the benefits and limitations of an intervention. Thirteen randomized clinical trials evaluated the role of prophylactic amiodarone in patients at risk of death from cardiac arrhythmias. Whereas 3 of these studies reported a reduction in mortality, several others revealed no benefits of amiodarone. Because neither trial was designed to detect reductions in total mortality, it remained unclear whether the beneficial effect of amiodarone on arrhythmic death and resuscitated ventricular fibrillation translated into a beneficial effect on total mortality. To address this, a meta-analysis was performed from the 13 trials of amiodarone in patients after an acute myocardial infarction or with congestive heart failure. The results showed a significant reduction in mortality and in arrhythmic death with amiodarone.