伐尼克兰戒烟有效性及安全性的Meta分析和试验序贯分析

Effectiveness and safety of varenicline on smoking cessation: a Meta-analysis with trial sequential analysis

目的:系统评价伐尼克兰戒烟的有效性、安全性及证据质量。方法:计算机检索PubMed、Web of Science、The Cochrane Library、Embase、CNKI、VIP、WanFang Data和CBM数据库,并补充检索参考文献,搜集有关伐尼克兰戒烟的随机对照试验(randomized controlled trials, RCTs),检索时限均为建库至2022年4月。由2名研究员独立筛选文献、提取资料并评价纳入研究的偏倚风险后,采用RevMan 5.3软件进行Meta分析,Stata 12.0软件进行发表偏倚检验,TSA v 0.9软件进行试验序贯分析,最后进行GRADE证据质量评价。结果:最终纳入51个RCTs,包括17 601例吸烟者。Meta分析结果显示,与安慰剂相比,伐尼克兰干预提高了持续戒断率[OR=2.57,95%CI(2.18,3.02),P<0.05,极低证据质量]和7天时点戒断率[OR=2.16,95%CI(1.87,2.49),P<0.05,极低证据质量]。亚组分析显示,伐尼克兰对患基础疾病吸烟者[OR=2.25,95%CI(1.85,2.74),P<0.05,极低证据质量]和一般吸烟者[OR=2.44,95%CI(2.06,2.89),P<0.05,极低证据质量]的干预均有效;同时,12、24和52周随访时间的持续戒断率和7天时点戒断率均有统计学意义(P<0.05)。试验序贯分析表明,伐尼克兰戒烟有效性确切。伐尼克兰常见不良反应为恶心、呕吐、梦境异常、睡眠障碍、头痛、抑郁、易怒、消化不良和鼻咽炎,差异具有统计学意义(P<0.05)。结论:现有证据支持伐尼克兰在戒烟方面优于安慰剂,不良反应大多为轻至中度,耐受性良好。建议未来开展更多伐尼克兰与其他干预联合治疗或比较的研究。

OBJECTIVE To systematically review the effectiveness and safety of varenicline on smoking cessation.METHODS Databases including PubMed, Web of Science, The Cochrane Library, Embase, CNKI,VIP,WanFang Data and CBM were searched from inception to April 2022,to collect randomized controlled trials(RCTs)on varenicline for smoking cessation.Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies.Then Meta-analysis was performed using RevMan 5.3 software, publication bias test was performed using Stata 12.0 software, trial sequential analysis(TSA)was performed using TSA 0.9 software, and the GRADE tool was used to evaluate the evidence quality.RESULTS A total of 51 RCTs involving 17 601 smokers were included.The results of Meta-analysis showed that, compared with the placebo, varenicline increases the continuous abstinence rate[OR=2.57,95%CI(2.18,3.02),P<0.05,very low quality]and 7-day point abstinence rate[OR=2.16,95%CI(1.87,2.49),P<0.05,very low quality].Subgroup analysis showed that, there were significant differences in smokers with basic diseases[OR=2.25,95%CI(1.85,2.74),P<0.05,very low quality]and healthy smokers[OR=2.44,95%CI(2.06,2.89),P<0.05,very low quality].And both the continuous abstinence rate and 7-day point abstinence rate at 12,24,52 weeks of follow-up showed significant differences.TSA showed varenicline had definite effectiveness on smoking cessation.Common adverse events were nausea, vomit, abnormal dreams, sleep disturbances, headache, depression, irritability, indigestion and nasopharyngitis(P<0.05).CONCLUSIONS Existing evidence supports that varenicline is superior to placebo in smoking cessation, and varenicline has mild to moderate adverse events and is well tolerated.It is suggested that more studies should be performed in the future on the combination therapy or comparison of varenicline with other interventions.