Hartmann-Boyce Jamie, McRobbie Hayden, Lindson Nicola, Bullen Chris, Begh Rachna, Theodoulou Annika, Notley Caitlin, Rigotti Nancy A, Turner Tari, Butler Ailsa R, Hajek Peter
Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK.
National Drug and Alcohol Research Centre, University of New South Wales, Sydney, Australia.
Cochrane Database Syst Rev. 2020 Oct 14;10(10):CD010216. doi: 10.1002/14651858.CD010216.pub4.
Electronic cigarettes (ECs) are handheld electronic vaping devices which produce an aerosol formed by heating an e-liquid. People who smoke report using ECs to stop or reduce smoking, but some organisations, advocacy groups and policymakers have discouraged this, citing lack of evidence of efficacy and safety. People who smoke, healthcare providers and regulators want to know if ECs can help people quit and if they are safe to use for this purpose. This review is an update of a review first published in 2014.
To evaluate the effect and safety of using electronic cigarettes (ECs) to help people who smoke achieve long-term smoking abstinence.
We searched the Cochrane Tobacco Addiction Group's Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and PsycINFO for relevant records to January 2020, together with reference-checking and contact with study authors.
We included randomized controlled trials (RCTs) and randomized cross-over trials in which people who smoke were randomized to an EC or control condition. We also included uncontrolled intervention studies in which all participants received an EC intervention. To be included, studies had to report abstinence from cigarettes at six months or longer and/or data on adverse events (AEs) or other markers of safety at one week or longer.
We followed standard Cochrane methods for screening and data extraction. Our primary outcome measures were abstinence from smoking after at least six months follow-up, AEs, and serious adverse events (SAEs). Secondary outcomes included changes in carbon monoxide, blood pressure, heart rate, blood oxygen saturation, lung function, and levels of known carcinogens/toxicants. We used a fixed-effect Mantel-Haenszel model to calculate the risk ratio (RR) with a 95% confidence interval (CI) for dichotomous outcomes. For continuous outcomes, we calculated mean differences. Where appropriate, we pooled data from these studies in meta-analyses.
We include 50 completed studies, representing 12,430 participants, of which 26 are RCTs. Thirty-five of the 50 included studies are new to this review update. Of the included studies, we rated four (all which contribute to our main comparisons) at low risk of bias overall, 37 at high risk overall (including the 24 non-randomized studies), and the remainder at unclear risk. There was moderate-certainty evidence, limited by imprecision, that quit rates were higher in people randomized to nicotine EC than in those randomized to nicotine replacement therapy (NRT) (risk ratio (RR) 1.69, 95% confidence interval (CI) 1.25 to 2.27; I = 0%; 3 studies, 1498 participants). In absolute terms, this might translate to an additional four successful quitters per 100 (95% CI 2 to 8). There was low-certainty evidence (limited by very serious imprecision) of no difference in the rate of adverse events (AEs) (RR 0.98, 95% CI 0.80 to 1.19; I = 0%; 2 studies, 485 participants). SAEs occurred rarely, with no evidence that their frequency differed between nicotine EC and NRT, but very serious imprecision led to low certainty in this finding (RR 1.37, 95% CI 0.77 to 2.41: I = n/a; 2 studies, 727 participants). There was moderate-certainty evidence, again limited by imprecision, that quit rates were higher in people randomized to nicotine EC than to non-nicotine EC (RR 1.71, 95% CI 1.00 to 2.92; I = 0%; 3 studies, 802 participants). In absolute terms, this might again lead to an additional four successful quitters per 100 (95% CI 0 to 12). These trials used EC with relatively low nicotine delivery. There was low-certainty evidence, limited by very serious imprecision, that there was no difference in the rate of AEs between these groups (RR 1.00, 95% CI 0.73 to 1.36; I = 0%; 2 studies, 346 participants). There was insufficient evidence to determine whether rates of SAEs differed between groups, due to very serious imprecision (RR 0.25, 95% CI 0.03 to 2.19; I = n/a; 4 studies, 494 participants). Compared to behavioural support only/no support, quit rates were higher for participants randomized to nicotine EC (RR 2.50, 95% CI 1.24 to 5.04; I = 0%; 4 studies, 2312 participants). In absolute terms this represents an increase of six per 100 (95% CI 1 to 14). However, this finding was very low-certainty, due to issues with imprecision and risk of bias. There was no evidence that the rate of SAEs varied, but some evidence that non-serious AEs were more common in people randomized to nicotine EC (AEs: RR 1.17, 95% CI 1.04 to 1.31; I = 28%; 3 studies, 516 participants; SAEs: RR 1.33, 95% CI 0.25 to 6.96; I = 17%; 5 studies, 842 participants). Data from non-randomized studies were consistent with RCT data. The most commonly reported AEs were throat/mouth irritation, headache, cough, and nausea, which tended to dissipate over time with continued use. Very few studies reported data on other outcomes or comparisons and hence evidence for these is limited, with confidence intervals often encompassing clinically significant harm and benefit.
AUTHORS' CONCLUSIONS: There is moderate-certainty evidence that ECs with nicotine increase quit rates compared to ECs without nicotine and compared to NRT. Evidence comparing nicotine EC with usual care/no treatment also suggests benefit, but is less certain. More studies are needed to confirm the degree of effect, particularly when using modern EC products. Confidence intervals were wide for data on AEs, SAEs and other safety markers. Overall incidence of SAEs was low across all study arms. We did not detect any clear evidence of harm from nicotine EC, but longest follow-up was two years and the overall number of studies was small. The main limitation of the evidence base remains imprecision due to the small number of RCTs, often with low event rates. Further RCTs are underway. To ensure the review continues to provide up-to-date information for decision-makers, this review is now a living systematic review. We will run searches monthly from December 2020, with the review updated as relevant new evidence becomes available. Please refer to the Cochrane Database of Systematic Reviews for the review's current status.
电子烟是一种手持电子雾化设备，通过加热电子液体产生气溶胶。吸烟者报告称使用电子烟来戒烟或减少吸烟量，但一些组织、倡导团体和政策制定者对此表示反对，理由是缺乏有效性和安全性证据。吸烟者、医疗服务提供者和监管机构都想知道电子烟是否能帮助人们戒烟，以及用于此目的是否安全。本综述是对2014年首次发表的一篇综述的更新。
评估使用电子烟帮助吸烟者实现长期戒烟的效果和安全性。
我们检索了Cochrane烟草成瘾小组专业注册库、Cochrane对照试验中央注册库（CENTRAL）、MEDLINE、Embase和PsycINFO，以获取截至2020年1月的相关记录，并进行参考文献核对和与研究作者联系。
我们纳入了随机对照试验（RCT）和随机交叉试验，其中吸烟者被随机分配到电子烟组或对照组。我们还纳入了所有参与者都接受电子烟干预的非对照干预研究。要纳入研究，必须报告六个月或更长时间的戒烟情况和/或一周或更长时间的不良事件（AE）或其他安全指标数据。
我们遵循Cochrane标准方法进行筛选和数据提取。我们的主要结局指标是至少随访六个月后的戒烟情况、AE和严重不良事件（SAE）。次要结局包括一氧化碳、血压、心率、血氧饱和度、肺功能以及已知致癌物/毒物水平的变化。我们使用固定效应Mantel-Haenszel模型计算二分结局的风险比（RR）及其95%置信区间（CI）。对于连续结局，我们计算平均差异。在适当情况下，我们将这些研究的数据合并进行荟萃分析。
我们纳入了50项完成的研究，共12430名参与者，其中26项为RCT。50项纳入研究中有35项是本次综述更新中的新增研究。在纳入的研究中，我们将四项研究（均对我们的主要比较有贡献）整体偏倚风险评为低，37项整体偏倚风险评为高（包括24项非随机研究），其余研究偏倚风险不明确。有中等确定性的证据表明，随机分配到含尼古丁电子烟组的人的戒烟率高于随机分配到尼古丁替代疗法（NRT）组的人，但证据因不精确性而受到限制（风险比（RR）1.69，95%置信区间（CI）1.25至2.27；I² = 0%；3项研究，1498名参与者）。从绝对数值来看，这可能意味着每100人中会额外增加4名成功戒烟者（95% CI 2至8）。有低确定性的证据（因非常严重的不精确性而受到限制）表明不良事件（AE）发生率无差异（RR 0.98，95% CI 0.80至1.19；I² = 0%；2项研究，485名参与者）。SAE很少发生，没有证据表明含尼古丁电子烟组和NRT组之间其发生率存在差异，但由于非常严重的不精确性，这一发现的确定性较低（RR 1.37，95% CI 0.77至2.41；I² = 无可用数据；2项研究，727名参与者）。有中等确定性的证据再次因不精确性而受到限制，表明随机分配到含尼古丁电子烟组的人的戒烟率高于非尼古丁电子烟组（RR 1.71，95% CI 1.00至2.92；I² = 0%；3项研究，802名参与者）。从绝对数值来看，这可能再次导致每100人中额外增加4名成功戒烟者（95% CI 0至12）。这些试验使用的电子烟尼古丁释放量相对较低。有低确定性的证据因非常严重的不精确性而受到限制，表明这些组之间AE发生率无差异（RR 1.00，95% CI 0.73至1.36；I² = 0%；2项研究，346名参与者）。由于非常严重的不精确性，没有足够的证据确定各组之间SAE发生率是否存在差异（RR 0.25，95% CI 0.03至2.19；I² = 无可用数据；4项研究，494名参与者）。与仅接受行为支持/无支持相比，随机分配到含尼古丁电子烟组的参与者戒烟率更高（RR 2.50，95% CI 1.24至5.04；I² = 0%；4项研究，2312名参与者）。从绝对数值来看这意味着每100人中增加6名（95% CI 1至14）。然而，由于不精确性和偏倚风险问题，这一发现的确定性非常低。没有证据表明SAE发生率有所不同，但有一些证据表明随机分配到含尼古丁电子烟组的人非严重AE更常见（AE：RR 1.17，95% CI 1.04至1.31；I² = 28%；3项研究，516名参与者；SAE：RR 1.33，95% CI 0.25至6.96；I² = 17%；5项研究，842名参与者）。非随机研究的数据与RCT数据一致。最常报告的AE是咽喉/口腔刺激、头痛、咳嗽和恶心，随着持续使用往往会随着时间消散。很少有研究报告其他结局或比较的数据，因此关于这些的证据有限，置信区间往往涵盖临床上显著的危害和益处。
有中等确定性的证据表明，与不含尼古丁的电子烟和NRT相比，含尼古丁的电子烟可提高戒烟率。将含尼古丁电子烟与常规护理/无治疗进行比较的证据也表明有好处，但确定性较低。需要更多研究来确认效果程度，特别是在使用现代电子烟产品时。关于AE、SAE和其他安全指标的数据置信区间较宽。所有研究组中SAE的总体发生率较低。我们未发现含尼古丁电子烟有任何明显危害证据，但最长随访时间为两年且研究总数较少。证据基础的主要局限性仍然是由于RCT数量少且事件发生率低导致的不精确性。更多RCT正在进行中。为确保本综述继续为决策者提供最新信息，本综述现为动态系统综述。我们将从2020年12月开始每月进行检索，随着相关新证据的出现对综述进行更新。请查阅Cochrane系统评价数据库以获取该综述当前状态。
