Electronic cigarettes and cardiovascular outcomes: a systematic review and meta-analysis of Major Adverse Cardiovascular Events (MACE)

Electronic Nicotine Delivery Systems (ENDS), including e-cigarettes, are increasingly used worldwide, yet their association with major adverse cardiovascular outcomes remains inconclusive. We conducted a systematic review and meta-analysis (PROSPERO: CRD420251026677) in accordance with PRISMA guidelines. PubMed, MEDLINE, Embase, and Scopus were searched up to May 10, 2025. Eligible studies included adolescents (13–18 years) and adults (≥ 19 years) using ENDS, reporting outcomes on any of the following: non-fatal myocardial infarction (MI), stroke, coronary artery disease (CAD), or cardiovascular mortality. The pooled odds ratios (ORs) were estimated using random-effects models and were considered the primary effect measures for assessing cardiovascular risk across exposure groups. Pooled outcome proportions were reported as secondary measures, reflecting the prevalence of outcomes within the ENDS-exposed population. Twenty-six studies, comprising over 900,000 ENDS users, were analyzed. The meta-analyses showed significantly higher pooled odds of coronary heart disease (OR = 1.19, p < 0.0001), major adverse cardiovascular events (MACE) (OR = 1.57, p < 0.0001), and stroke (OR = 1.62, p < 0.01). The greatest risk was observed among dual users (OR = 2.21, p < 0.0001.), indicating additive cardiovascular harm associated with combined use. All outcomes demonstrated substantial heterogeneity between-study variability. ENDS use is associated with potential cardiovascular harm, particularly regarding stroke and non-fatal MI; however, the overall findings are limited by substantial heterogeneity. Associations with CAD and mortality remain inconclusive due to data limitations. High-quality longitudinal studies are needed to clarify the long-term cardiovascular risks of ENDS, which could ultimately guide public health policies and initiatives.