Dual Use of Electronic and Combustible Cigarettes and Stroke Risk: A Systematic Review and Meta-analysis

Dual use of electronic cigarettes and combustible cigarettes is increasingly prevalent, yet its association with stroke and other cardiovascular outcomes remains unclear. This study evaluated the association of dual use with stroke and other cardiovascular outcomes compared with never smoking through a systematic review and meta-analysis.

Ovid-MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, KoreaMed, and the International Clinical Trials Registry Platform were searched from 2003 to September 2025. Comparative studies reporting adjusted effect estimates for cardiovascular or cerebrovascular outcomes among adults were eligible. When at least five methodologically comparable studies were available, a random-effects meta-analysis using restricted maximum likelihood estimation was conducted. Heterogeneity was assessed using Cochran's Q and Higgins' I² statistics. Leave-one-out analyses evaluated robustness.

Ten observational studies were included (four prospective cohort and six cross-sectional studies). Seven studies reported stroke outcomes. In pooled analyses of cross-sectional studies, dual use was associated with higher odds of stroke compared with never smoking (adjusted odds ratio, 1.90; 95% confidence interval [CI], 1.50-2.40), with substantial heterogeneity (I²=91.3%). Leave-one-out analyses showed consistent results. Composite cardiovascular outcomes suggested elevated risk but were not pooled because of substantial variability in outcome definitions. One prospective cohort study reported increased all-cause mortality (adjusted hazard ratio, 2.44; 95% CI, 1.90-3.13).

Dual use of electronic and combustible cigarettes was associated with increased odds of stroke compared with never smoking, although the evidence was predominantly cross-sectional and showed substantial heterogeneity. Prospective studies with standardized exposure definitions and validated cardiovascular outcomes are needed to clarify long-term cardiovascular risk.