European Heart Journal Advance Access originally published online on November 2, 2007
European Heart Journal 2007 28(24):3012-3019; doi:10.1093/eurheartj/ehm489
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Quantitative relationship between resting heart rate reduction and magnitude of clinical benefits in post-myocardial infarction: a meta-regression of randomized clinical trials
Faculté de médecine Laennec, EA3736—Université Lyon 1, 11 rue Guillaume Paradin, 69008 Lyon France
Received 12 June 2007; revised 13 September 2007; accepted 26 September 2007; online publish-ahead-of-print 2 November 2007.
Corresponding author. Tel: +33 4 78 78 57 71; fax: +33 4 78 77 69 17. E-mail address: mcu{at}upcl.univ-lyon1.fr
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.
Key Words: Meta-regression • Resting heart rate reduction • Beta-blockers • Calcium channel blockers • Meta-analysis • Mortality
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