Highlight
- Nicotine e-cigarettes (EC) demonstrate higher smoking quit rates than nicotine replacement therapy (NRT) and non-nicotine EC.
- No detected difference in serious adverse events (SAEs) between EC and comparators, though evidence for safety remains low certainty.
- Living systematic review approach ensures continuous updating with emerging evidence.
- Main safety concerns include mild adverse events that often resolve with continued use.
Background
Tobacco use remains one of the leading preventable causes of morbidity and mortality worldwide, accounting for millions of deaths annually through cardiovascular disease, respiratory illness, and cancer. Smoking cessation interventions are key to reducing this burden. Electronic cigarettes (EC), also known as vaping devices, deliver aerosolized nicotine without combustion, potentially reducing exposure to harmful tobacco smoke constituents. There remains debate among clinicians, regulators, and public health experts regarding the effectiveness and safety of EC for smoking cessation.
Study Design
This updated Cochrane living systematic review, conducted to March 2025, evaluated the safety, tolerability, and effectiveness of nicotine-containing EC compared to non-nicotine EC, other smoking cessation aids (including NRT), and no intervention or behavioral support alone. Databases searched included CENTRAL, MEDLINE, Embase, and PsycINFO, supplemented by additional reference checks and author contact. Eligible studies included randomized controlled trials (RCTs) and uncontrolled intervention studies with measurable smoking cessation or safety outcomes. The primary endpoint was smoking abstinence at ≥6 months, with secondary outcomes including adverse events, SAEs, biomarkers of exposure, and patterns of longer-term EC use. Risk of bias was assessed via the Cochrane RoB 1 tool, with evidence certainty graded using GRADE methodology. Statistical synthesis utilized random-effects models to estimate pooled risk ratios (RRs) and mean differences where applicable.
Key Findings
Nicotine EC vs Nicotine Replacement Therapy
High-certainty evidence from nine RCTs (n=2703) indicated nicotine EC increased quit rates compared to NRT (RR 1.55, 95% CI 1.28–1.88; I²=0%). In absolute terms, this equates to three additional quitters per 100 users (95% CI 2–5 more). Rates of adverse events were likely similar between groups (RR 1.00, 95% CI 0.73–1.37; moderate-certainty). SAEs were rare, with low-certainty evidence preventing firm conclusions on comparative risk (RR 1.22, 95% CI 0.73–2.03).
Nicotine EC vs Non-Nicotine EC
Moderate-certainty evidence (n=1918, 7 studies) suggested nicotine EC improved quit rates relative to non-nicotine EC (RR 1.34, 95% CI 1.06–1.70; I²=0%), representing two additional quitters per 100 (95% CI 0–4 more). Adverse events likely occurred at similar rates (RR 1.01, 95% CI 0.95–1.08), with insufficient evidence for SAEs due to low event rates (RR 0.98, 95% CI 0.55–1.73).
Nicotine EC vs Behavioral Support Only or No Support
Low-certainty evidence (n=6819, 11 studies) indicated nicotine EC may increase quit rates over behavioral support/no support (RR 1.78, 95% CI 1.42–2.25). This translates to roughly three more quitters per 100 (95% CI 2–5). The review found uncertain evidence for increased non-serious adverse events (RR 1.22, 95% CI 0.96–1.55) and no definitive difference in SAE rates (RR 0.93, 95% CI 0.67–1.29).
Safety Profile
Commonly reported adverse events included throat/mouth irritation, headache, cough, and nausea — symptoms that typically resolved with ongoing EC use. Across all evaluated interventions, SAEs were infrequent. Importantly, all evaluated products were regulated nicotine-containing EC; illicit or THC-containing products may present distinct risks not captured here.
Expert Commentary
This extensive review consolidates the highest level of available evidence, strongly supporting the efficacy of regulated nicotine EC as a cessation aid over traditional NRT. However, the safety profile remains incompletely understood, particularly in relation to long-term use and rare adverse events, reflecting low-certainty evidence in those domains. Clinicians should interpret results within the context of regulated products; generalization to unregulated or modified EC devices is not warranted. The living systematic review framework is critical, as EC devices evolve rapidly and ongoing trials may provide more precise estimates regarding safety endpoints. Given the consistent alignment between non-randomized and randomized evidence, translational practice could cautiously incorporate nicotine EC into cessation protocols, prioritizing patient-informed choice and regulatory oversight.
Conclusion
Nicotine EC demonstrate superior quit rates compared to both NRT and non-nicotine EC, with potential benefits over behavioral support alone, although certainty varies between comparisons. Safety findings are reassuring regarding the absence of detected serious harm, but remain limited by imprecision. Continued surveillance, larger RCTs, and evaluation of long-term physiological outcomes are necessary. Regulatory bodies and healthcare providers should balance the clear efficacy signal against remaining safety uncertainties, tailoring recommendations to product quality and patient-specific considerations.
Funding and Protocol Registration
Funding: Cancer Research UK (PICCTR-2024/100012). Protocols registered and available via DOI: 10.1002/14651858.CD010216, 10.17605/OSF.IO/ZWGSK, 10.17605/OSF.IO/59M4U, and 10.17605/OSF.IO/UPGJC.
References
Lindson N, Livingstone-Banks J, Butler AR, McRobbie H, Bullen CR, Hajek P, Wu AD, Begh R, Theodoulou A, Notley C, Rigotti NA, Turner T, Fanshawe T, Hartmann-Boyce J. Electronic cigarettes for smoking cessation. Cochrane Database Syst Rev. 2025 Nov 10;11(11):CD010216. doi: 10.1002/14651858.CD010216.pub10. PMID: 41212103; PMCID: PMC12599494.
