Cardiovascular Safety of Varenicline, Bupropion, and Nicotine Patch in Smokers A Randomized Clinical Trial
Cardiovascular Safety of Varenicline, Bupropion, and Nicotine Patch in Smokers A Randomized Clinical Trial
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DOI：
10.1001/jamainternmed.2018.0397
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发表时间：
2018-05-01
影响因子：
39
通讯作者：
Anthenelli, Robert M.
中科院分区：
文献类型：
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作者：
Benowitz, Neal L.;Pipe, Andrew;Anthenelli, Robert M.
重要性通过使用药物治疗来增强戒烟，但是已经提出了关于这些药物的心血管安全性的担忧。安慰剂和活性对照试验（评估全球戒烟研究[EAGLES]中的不良事件）及其非治疗扩展试验在140个多国中心进行。吸烟者，有或没有确定的精神病诊断，接受至少1剂研究药物（n = 8058），以及完成12周治疗加12周随访并同意再随访28周的患者子集干预伐尼克兰1 mg，2次/d，盐酸安非他酮150 mg，2次/d;尼古丁替代疗法，21-mg/d贴剂，逐渐减量。主要结果和指标主要终点是发生主要不良心血管事件的时间（MACE：心血管死亡、非致死性心肌梗死或非致死性卒中）;次要终点为MACE和其他相关心血管事件的发生率（MACE+：MACE或新发或恶化的外周血管疾病，需要介入治疗、冠状动脉血运重建或因不稳定型心绞痛住院治疗）。3553例（44.1%）为男性（平均[SD]年龄，46.5 [12.3]岁）。治疗和随访期间心血管事件的发生率较低（MACE < 0.5%; MACE +< 0.8%），并且治疗之间无显著差异。在至心血管事件、血压或心率的时间方面，未观察到显著的治疗差异。与安慰剂相比，伐尼克兰或安非他酮治疗组至发生MACE的时间无显著差异（伐尼克兰：风险比，0.29; 95% CI，0.05-1.68;安非他酮：风险比，0.50; 95%可信区间，0.10-2.50）结论和相关性没有证据表明使用戒烟药物治疗会增加严重心血管不良事件的风险。治疗期间或治疗后观察。EAGLES及其扩展试验的结果提供了进一步的证据，表明戒烟药物不会增加一般吸烟人群发生严重心血管事件的风险。
IMPORTANCE Quitting smoking is enhanced by the use of pharmacotherapies, but concerns have been raised regarding the cardiovascular safety of such medications.OBJECTIVE To compare the relative cardiovascular safety risk of smoking cessation treatments.DESIGN, SETTING, AND PARTICIPANTS A double-blind, randomized, triple-dummy, placeboand active- controlled trial (Evaluating Adverse Events in a Global Smoking Cessation Study [EAGLES]) and its nontreatment extension trial was conducted at 140 multinational centers. Smokers, with or without established psychiatric diagnoses, who received at least 1 dose of study medication (n = 8058), as well as a subset of those who completed 12 weeks of treatment plus 12 weeks of follow up and agreed to be followed up for an additional 28 weeks (n = 4595), were included.INTERVENTIONS Varenicline, 1mg twice daily; bupropion hydrochloride, 150mg twice daily; and nicotine replacement therapy, 21-mg/d patch with tapering.MAIN OUTCOMES AND MEASURES The primary end pointwas the time to development of a major adverse cardiovascular event (MACE: cardiovascular death, nonfatalmyocardial infarction, or nonfatal stroke) during treatment; secondary end points were the occurrence of MACE and other pertinent cardiovascular events (MACE+: MACE or new-onset or worsening peripheral vascular disease requiring intervention, coronary revascularization, or hospitalization for unstable angina).RESULTS Of the 8058 participants, 3553 (44.1%) were male (mean [SD] age, 46.5 [12.3] years). The incidence of cardiovascular events during treatment and follow- up was low (< 0.5% for MACE; < 0.8% forMACE+) and did not differ significantly by treatment. No significant treatment differences were observed in time to cardiovascular events, blood pressure, or heart rate. There was no significant difference in time to onset ofMACE for either varenicline or bupropion treatment vs placebo (varenicline: hazard ratio, 0.29; 95% CI, 0.05-1.68 and bupropion: hazard ratio, 0.50; 95% CI, 0.10-2.50).CONCLUSIONS AND RELEVANCE No evidence that the use of smoking cessation pharmacotherapies increased the risk of serious cardiovascular adverse events during or after treatment was observed. The findings of EAGLES and its extension trial provide further evidence that smoking cessation medications do not increase the risk of serious cardiovascular events in the general population of smokers.