Safety of ivabradine, a heart rate lowering drug: a systematic review and meta-analysis

doi:10.5246/jcps.2017.05.041

Abstract

Abstract:

As a novel heart rate lowing agent, ivabradine can reduce the heart rate by inhibiting the I_f (pacemaker) current in the sinoatrial node without affecting blood pressure or left ventricular systolic function. However, the safety of ivabradine remains controversial. In the present work, we aimed to assess any risk of cardiovascular mortality, bradycardia, phosphenes and atrial fibrillation associated with the ivabradine administration by meta-analysis. Studies were retrieved from PubMed, EMBASE, MEDLINE, Web of Science, Cochrane, www.clinicaltrials.gov web site and related conferences. Randomized controlled trials comparing ivabradine with comparators were identified and analyzed. Two reviewers independently extracted relevant informationfrom the eligible trials and processed the data. This meta-analysis was performed by using Review Manager (5.3) and Stata (14.1) software. Moreover, sensitivity analysis and publication bias of the included studies were evaluated. A total of 12 randomized controlled trials meeting the inclusion criteria were included. Results of the meta-analysis revealed that there was no significant difference between ivabradine group and control groups in cardiovascular mortality (RR = 0.97, 95% CI: 0.89-1.06, P = 0.49). While the administration of ivabradine was associated with a significant increase in the incidence of bradycardia (RR = 3.90, 95% CI: 2.47-6.17, P<0.00001) and phosphenes (RR = 4.95, 95% CI: 3.24-7.55, P<0.00001) as well as atrial fibrillation (RR = 1.24,95% CI: 1.07-1.43, P = 0.003). High quality of the included studies was confirmed by quality assessment. No publication bias was observed, and sensitivity analysis confirmed that the obtained results were stable. In conclusion, the meta-analysis proved that the use of ivabradine was associated with a significant increase in the risk of bradycardia, phosphenes and atrial fibrillation. Therefore, clinicians need to take these risks into account when using ivabradine in treatment.

Key words: Ivabradine, Systematic review, Meta-analysis, Safety

CLC Number:

R969.4

Supporting:

Ruirui Xiao, Xiuqin Xu, Lei Sun, Xiaolei Fang, Peng Xiao. Safety of ivabradine, a heart rate lowering drug: a systematic review and meta-analysis[J]. Journal of Chinese Pharmaceutical Sciences, 2017, 26(5): 379-389.

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