Cardiovascular Safety of Varenicline: Patient-Level Meta-Analysis of Randomized, Blinded, Placebo-Controlled Trials
Cardiovascular Safety of Varenicline: Patient-Level Meta-Analysis of Randomized, Blinded, Placebo-Controlled Trials
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伐尼克兰的心血管安全性：随机、盲法、安慰剂对照试验的患者水平荟萃分析
DOI：
10.1097/mjt.0b013e31828d455b
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发表时间：
2013
影响因子：
4.2
通讯作者：
J. Borer
中科院分区：
文献类型：
--
作者：
J. Ware;G. Vetrovec;Alan Miller;A. Van Tosh;M. Gaffney;C. Yunis;C. Arteaga;J. Borer
吸烟是心血管（CV）疾病的主要可改变风险因素。伐伦克林是一种戒烟的药物辅助剂。为了探索伐尼克兰的CV安全性，我们研究了在年龄≥18岁的吸烟者中进行的、由药品制造商申办的、治疗持续时间≥12周的所有2-4期随机安慰剂对照临床试验中伐尼克兰治疗受试者的CV事件发生率。这篇手稿报告了一项受试者水平的至重大心血管不良事件（MACE;定义为CV相关死亡、非致死性心肌梗死、非致死性卒中）时间和至MACE+（定义为MACE+外周血管疾病恶化或任何手术、因心绞痛住院或进行冠状动脉血运重建）时间的荟萃分析。所有事件均由独立裁定委员会裁定，该委员会对治疗分配不知情。在治疗期间和末次治疗给药后30天内评估事件。主要分析方法是分层对数秩至事件时间分析;次要分析是发生率比值和发生率差异的荟萃分析。总体而言，15项研究纳入了7002例受试者（伐尼克兰：4190例;安慰剂：2812例）。13例伐尼克兰受试者（0.31%）和6例安慰剂受试者（0.21%）报告了MACE [风险比，1.95; 95%置信区间（CI）：0.79-4.82; P = 0.15;风险差，0.006起事件/受试者-年; 95% CI：-0.003，0.015，P = 0.19]。26例伐尼克兰受试者（0.62%）和12例安慰剂受试者（0.43%）报告了MACE+（风险比，1.74; 95% CI：0.91-3.34，P = 0.10;风险差，0.010; 95% CI：−0.002，0.022，P = 0.11）。在伐尼克兰的安慰剂对照临床试验中，对治疗后30天的MACE或MACE+进行了受试者水平的荟萃分析，发现伐尼克兰治疗患者中这些事件的发生率有增加的趋势，但未达到统计学显著性。事件总数较低，伐尼克兰CV事件的绝对风险较小。
Smoking is a major modifiable risk factor for cardiovascular (CV) disease. Varenicline is a pharmacological aid for smoking cessation. To explore the CV safety of varenicline, we investigated the incidence of CV events in varenicline-treated subjects across all phase 2–4 randomized placebo-controlled clinical trials of ≥12-week treatment duration conducted in smokers aged ≥18 years and sponsored by the drug manufacturer. This manuscript reports a subject-level meta-analysis of time to major adverse cardiovascular events (MACE; defined as CV-related death, nonfatal myocardial infarction, nonfatal stroke) and time to MACE+ (defined as MACE plus worsening or any procedure for peripheral vascular disease, hospitalization for angina, or performance of coronary revascularization). All events were adjudicated by an independent adjudication committee, blind to treatment assignment. Events were assessed during treatment and up to 30 days after the last treatment dose. The primary analytical method was a stratified logrank time-to-event analysis; secondary analyses were meta-analyses of incidence rate ratios and rate differences. Overall, 7002 subjects were included (varenicline: 4190; placebo: 2812) from 15 studies. MACE were reported by 13 varenicline subjects (0.31%) and 6 placebo subjects (0.21%) [hazard ratio, 1.95; 95% confidence interval (CI): 0.79–4.82; P = 0.15; risk difference, 0.006 events per subject-year; 95% CI: −0.003, 0.015, P = 0.19]. MACE+ were reported by 26 varenicline subjects (0.62%) and 12 placebo subjects (0.43%) (hazard ratio, 1.74; 95% CI: 0.91–3.34, P = 0.10; risk difference, 0.010; 95% CI: −0.002, 0.022, P = 0.11). This subject-level meta-analysis of MACE or MACE+ up to 30 days posttreatment in placebo-controlled clinical trials of varenicline found a trend toward increased incidence of these events in varenicline-treated patients that did not reach statistical significance. The overall number of events was low and the absolute risk of CV events with varenicline was small.