Quantitative relationship between resting heart rate reduction and magnitude of clinical benefits in post-myocardial infarction: a meta-regression of randomized clinical trials

Aims The impact on mortality outcomes of beta-blockers and calcium blockers in post-myocardial infarction (MI) has been suggested to be related to resting heart rate (HR) reduction. A meta-regression of randomized clinical trials was carried out to assess this relationship using weighted meta-regression of logarithm of odds ratio against absolute HR reduction. Methods and results Twenty-five controlled randomized trials (21 with beta-blockers and four with calcium channel blockers) involving a total of 30 904 patients meet eligibility criteria, but only 17 documented changes in resting HR (14 with beta-blockers and three with calcium channel blockers). A statistically significant relationship was found between resting HR reduction and the clinical benefit including reduction in cardiac death (P < 0.001), all-cause death (P = 0.008), sudden death (P = 0.015), and non-fatal MI recurrence (P = 0.024). Each 10 b.p.m. reduction in the HR is estimated to reduce the relative risk of cardiac death by 30%. Conclusion The meta-regression of the randomized clinical trials strongly suggest that the beneficial effect of beta-blockers and calcium channel blockers in post-MI patients is proportionally related to resting HR reduction. Furthermore, the absence of residual heterogeneity indicated that resting HR reduction could be a major determinant of the clinical benefit.