Importance of heart rate in determining beta-blocker efficacy in acute and long-term acute myocardial infarction intervention trials

Abstract

Heart rate after an acute myocardial infarction (AMI) is an index of late mortality. The hypothesis--that the potential beneficial effect of beta-blocking drugs after an AMI is quantitatively dependent on the reduction of heart rate obtained by such treatment--was examined by reviewing available data from acute and long-term intervention trials. Only properly randomized and double-blind trials were considered. In acute intervention trials only patients who received treatment within 12 hours after onset of pain were included. In early intervention trials there was a close relation between the reduction in heart rate and infarct size as determined by accumulated creatine kinase release (r = 0.97, p less than 0.001). A reduction in heart rate of at least 15 beats/min during infarct evolution was associated with a reduction of infarct size between 25 and 30%. The data suggest that a reduction in heart rate less than 8 beats/min has no effect or may actually increase infarct size. Comparison of post-AMI trials indicated a relation between the actual reduction of resting heart rate and percentage of reduction in mortality obtained in each trial (r = 0.60, p less than 0.05). An almost similar relation was demonstrated between the reduction in resting heart rate and nonfatal reinfarctions (r = 0.59, p less than 0.05). Confounding properties of a beta blocker, such as intrinsic sympathomimetic activity or prolongation of the QT interval, may reduce its efficacy. These results strongly suggest that the beneficial effect of beta blockers is related to a quantitative reduction in heart rate, probably indicating an antiischemic effect. However, the data do not exclude the possibility that other protective mechanisms may be operative.