Effects of prophylactic antiarrhythmic drug therapy in acute myocardial infarction. An overview of results from randomized controlled trials

Abstract

OBJECTIVE: To investigate the effects of prophylactic therapy with antiarrhythmic agents on mortality in patients with myocardial infarction. DATA SOURCES AND STUDY SELECTION: Data were obtained from all completed, published or unpublished, randomized, parallel controlled trials of antiarrhythmic agents, regardless of sample size. Investigators were contacted for data on patients excluded after randomization. DATA EXTRACTION: Data on mortality were extracted by one author and confirmed where necessary by the others. DATA SYNTHESIS: Mortality data from 138 trials on 98,000 patients were combined by the Yusuf-Peto adaptation of the Mantel-Haenszel method. There were 660 deaths among 11,712 patients allocated to receive class I agents and 571 deaths among 11,517 corresponding control patients (51 trials: odds ratio [OR], 1.14; 95% confidence interval [CI], 1.01 to 1.28; P = .03). Of 26,973 patients allocated to receive beta-blockers (class II agents), 1464 died compared with 1727 deaths among 26,295 control patients (55 trials: OR, 0.81; 95% CI, 0.75 to 0.87; P = .00001). Of 778 patients allocated to receive amiodarone (a class III agent), 77 died compared with 101 deaths in 779 control patients (eight trials: OR, 0.71; 95% CI, 0.51 to 0.97; P = .03). There were 982 deaths in 10,154 patients allocated to receive a class IV agent (calcium channel blockers) and 949 deaths in 10,188 control patients (24 trials: OR, 1.04; 95% CI, 0.95 to 1.14; P = .41). CONCLUSIONS: The routine use of class I antiarrhythmic agents after myocardial infarction is associated with increased mortality. beta-Blockers have been conclusively demonstrated to reduce mortality. The limited data on amiodarone appear promising. Data on calcium channel blockers remain unpromising.