Abstract
We investigated the comparative effects of smoking status on outcomes in older Chinese men receiving aspirin or clopidogrel monotherapy. This was a prospective observational study of outcomes in 668 men aged ≥ 60 years undergoing annual health examination in the Chinese People’s Liberation Army General Hospital from March–April 2017. All patients received regular treatment with aspirin or clopidogrel. Platelet aggregation and phenotyping for rs762551 were measured in all patients. We recorded all major adverse cardiovascular and cerebrovascular events; namely, all-cause death, myocardial infarction, stroke, transient ischemic attack, and unstable angina. In the clopidogrel subgroup, homozygous carriers (AA) of the CYP1A2*1F gene (rs762551, 163C>A) appeared more frequently in smokers than in nonsmokers (45.6% vs 32.7%, p = .035). Adenosine diphosphate-induced platelet aggregation using light transmittance aggregometry was lower in smokers compared with nonsmokers (44.97 ± 20.05% vs 51.98 ± 19.38%, respectively; p = .0018). Smokers (n = 103) had a decreased risk of major adverse cardiovascular and cerebrovascular events, compared with nonsmokers [n = 159; hazard ratio, 0.466; 95% confidence interval: 0.262–0.829, p = .008]. In the aspirin subgroup, AA-induced platelet aggregation showed no significant difference regarding smoking vs nonsmoking status (30.90 ± 32.21 vs 29.78 ± 31.47, respectively; p = .771). However, we saw a significant increase in adverse clinical events in the smoking group (n = 148) compared with the nonsmoking group (n = 258; hazard ratio = 1.907, 95% confidence interval: 1.128–3.225; p = .016). In older Chinese men, active smokers benefitted from clopidogrel therapy compared with aspirin. Long-term cigarette smoking may contribute to increased variations in CYP1A2*1F, but the variations do not fully explain the smoking paradox.
Acknowledgements
We thank Jane Charbonneau, DVM, from Liwen Bianji, Edanz Group China (www.liwenbianji.cn/ac), for editing the English text of a draft of this manuscript.
Disclosure of Interest Statement
All authors have no declarations of interest to report.
Statement of contribution
Yulun Cai and Hongbin Liu designed the protocol; Yulun Cai and Fan Wang drafted the manuscript; Lina Han, Hunan Xiao supervised patient recruitment and study procedures; Yuerui Li, Huiying Li, Man Li and Lei Duan conducted study procedures; Yulun Cai and Weihao Xu designed the statistical analyses and analyzed the data; all authors carried out study procedures, critically revised the manuscript for important intellectual content and approved the final manuscript.