Therapeutics Initiative, University of British Columbia, Vancouver, BC, Canada.
Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver, BC, Canada.
Nicotine Tob Res. 2021 Jan 22;23(2):302-309. doi: 10.1093/ntr/ntaa100.
The British Columbia Ministry of Health launched a Smoking Cessation Program on September 30, 2011, providing financial coverage for smoking cessation pharmacotherapies. Although pharmacotherapies have been shown to have a moderate short-term benefit as a quitting aid, substantial cardiovascular and neuropsychiatric safety concerns have been identified in adverse-reporting databases, leading to prescription label warnings by Health Canada and the U.S. Food and Drug Administration. However, recent studies indicate these warnings may be without merit. This study examined the comparative safety of medications commonly used to aid smoking cessation.
Population-based retrospective cohort study using B.C. administrative data to assess the relative safety between varenicline, bupropion, and nicotine replacement therapies (NRTs). The primary outcome was a composite of cardiovascular hospitalizations. Secondary outcomes included mortality, a composite of neuropsychiatric hospitalizations, and individual components of the primary outcome. Statistical analysis used propensity score-adjusted log-binomial regression models. A sensitivity analysis excluded patients with a history of cardiovascular disease.
The study included 116 442 participants. Compared with NRT, varenicline was associated with a 10% 1-year relative risk decrease of cardiovascular hospitalization (adjusted risk ratio [RR] = 0.90, 95% confidence interval (CI): 0.82 to 1.00), a 20% 1-year relative risk decrease of neuropsychiatric hospitalization (RR: 0.80, CI: 0.7 to 0.89), and a 19% 1-year relative risk decrease of mortality (RR: 0.81, CI: 0.71 to 0.93). We found no significant association between NRT and bupropion for cardiovascular hospitalizations, neuropsychiatric hospitalizations, or mortality.
Compared with NRT, varenicline is associated with fewer serious adverse events and bupropion the same number of serious adverse events.
This study addresses the need for comparative safety evidence in a real-world setting of varenicline and bupropion against an active comparator. Compared with NRT, varenicline was associated with a decreased risk of mortality, serious cardiovascular events, and neuropsychiatric events during the treatment, or shortly after the treatment, in the general population of adults seeking pharmacotherapy to aid smoking cessation. These results provide support for the removal of the varenicline boxed warning for neuropsychiatric events and add substantively to the cardiovascular safety findings of previous observational studies and randomized clinical trials.
不列颠哥伦比亚省卫生部于 2011 年 9 月 30 日启动了戒烟计划，为戒烟药物治疗提供资金支持。尽管药物治疗已被证明在短期内作为戒烟辅助具有适度的益处，但在不良报告数据库中已发现大量心血管和神经精神安全问题，这导致加拿大卫生部和美国食品和药物管理局发出处方标签警告。然而，最近的研究表明，这些警告可能没有根据。本研究检查了常用于帮助戒烟的药物的相对安全性。
使用不列颠哥伦比亚省行政数据进行基于人群的回顾性队列研究，以评估伐尼克兰、安非他酮和尼古丁替代疗法（NRT）之间的相对安全性。主要结局是心血管住院的综合结果。次要结局包括死亡率、神经精神住院的综合结果以及主要结局的各个组成部分。统计分析采用倾向评分调整的对数二项式回归模型。一项敏感性分析排除了有心血管疾病史的患者。
该研究纳入了 116442 名参与者。与 NRT 相比，伐尼克兰与 1 年相对风险降低 10%的心血管住院有关（调整后的风险比[RR] = 0.90，95%置信区间[CI]：0.82 至 1.00），1 年相对风险降低 20%的神经精神住院（RR：0.80，CI：0.70 至 0.89），以及 1 年相对风险降低 19%的死亡率（RR：0.81，CI：0.71 至 0.93）。我们没有发现 NRT 与安非他酮在心血管住院、神经精神住院或死亡率方面有显著关联。
与 NRT 相比，伐尼克兰与较少的严重不良事件相关，而安非他酮则有相同数量的严重不良事件。
本研究在现实环境中针对伐尼克兰和安非他酮与活性对照药物进行了比较安全性证据，满足了这一需求。与 NRT 相比，伐尼克兰与死亡率、严重心血管事件和神经精神事件风险降低相关，在一般寻求药物治疗辅助戒烟的成年人中，在治疗期间或治疗后不久，风险降低。这些结果为去除伐尼克兰的神经精神事件警示框提供了支持，并为之前的观察性研究和随机临床试验的心血管安全性发现提供了实质性补充。
