Effectiveness and Safety of Platelet ADP–P2Y12 Receptor Inhibitors Influenced by Smoking Status: A Systematic Review and Meta‐Analysis

BACKGROUND: As reports on the influence of cigarette smoking, an important cardiovascular risk factor, on platelet ADP–P2Y12 receptor inhibitors lack consistency, we aimed to assess the effectiveness and safety of platelet ADP–P2Y12 receptor inhibitors influenced by smoking status. METHODS AND RESULTS: PubMed, Web of Science, EMBASE, Clinical Trials, and the Cochrane Library were searched from inception until June 2018. Among the 5076 citations retrieved, 22 studies, including 163 011 patients with or without percutaneous coronary intervention, were included for meta‐analysis. Compared with nonsmokers within the first year of follow‐up, the reductions of stroke and major adverse cardiovascular event rate were 18% (P=0.008) and 26% (P=0.02), respectively. A 20% reduction in stroke (P=0.02) and a 34% reduction in major adverse cardiovascular event (P=0.0001) rates were observed in smoking patients without percutaneous coronary intervention. No significant difference was observed in clinical outcome rates among prasugrel, ticagrelor, and clopidogrel in different smoking status. No significant difference was found in myocardial infarction and bleeding event incidence between current smokers and nonsmokers. CONCLUSIONS: We concluded that current smokers had a lower incidence of major adverse cardiovascular events and stroke events than did nonsmokers, particularly in the early period (1 year) and among patients without percutaneous coronary intervention. However, because of the lack of original adjusted data, smoker's paradox still needs to consider the impact of age and other covariates. Thus, a differential risk‐benefit evaluation should be considered, according to different smoking status, patient conditions, and therapy time points.