降心率药物伊伐布雷定安全性的系统评价

doi:10.5246/jcps.2017.05.041

摘要/Abstract

摘要：

新型降心率药物伊伐布雷定通过抑制窦房结I_f电流发挥降心率作用, 并不影响血压及左室射血分数, 但该药物的安全性仍存在较大争议。因此本研究通过进行Meta分析评价其心血管死亡率、心动过缓、光幻视及房颤发生风险。研究者从PubMed, EMBASE, MEDLINE, Web of Science, Cochrane, www.clinicaltrials.gov等数据库中检索有关伊伐布雷定相比对照药物的随机对照试验, 两名研究者从所纳入的随机对照试验中提取信息, 利用Review Manager (5.3) 及Stata (14.1)软件进行Meta分析。此外, 对纳入研究也进行了敏感性分析及发表偏倚检测。本研究共纳入12项随对照试验, Meta分析结果证实伊伐布雷定相比对照药物在心血管死亡率方面无显著性差别(RR = 0.97, 95% CI: 0.89-1.06, P = 0.49)。然而伊伐布雷定所致心动过缓(RR = 3.90, 95% CI: 2.47-6.17, P<0.00001)、光幻视(RR = 4.95, 95% CI: 3.24-7.55, P<0.00001)及房颤(RR = 1.24, 95% CI: 1.07-1.43, P = 0.003)发生率均明显高于对照药物。质量评价也证实本研究所纳入的随机独照试验为高质量研究, 另外本研究无发表偏倚存在, 敏感性分析也表明结果稳健。简言之, 伊伐布雷定所致心动过缓、光幻视及房颤风险较高, 因此临床医师在使用中需要充分权衡利弊。

关键词: 伊伐布雷定, 系统评价, Meta分析, 安全性

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

中图分类号:

R969.4

Supporting:

肖锐锐, 徐秀琴, 孙磊, 方晓磊, 肖鹏. 降心率药物伊伐布雷定安全性的系统评价[J]. 中国药学(英文版), 2017, 26(5): 379-389.

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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