Effect of Smoking Status on Clinical Outcome and Efficacy of Clopidogrel in Acute Coronary Syndrome

Prognostic Factors in Patients With Stemi Undergoing Primary PCI in the Clopidogrel Era: Role of Dual Antiplatelet Therapy at Admission and the Smoking Paradox on Long‐Term Outcome

“…This effect was even more pronounced in high‐risk patients, especially those with ACS; this has been defined as “the smoking paradox.” The reasons for this paradoxical effect of smoking are not completely known, but could be related to an induction of CYP1A2 by cigarette smoking, which would lead to an increased production of the active metabolite of clopidogrel . However, the interaction of smoking in patients with ACS remains controversial, with recent studies having questioned the role of smoking as a positive prognostic factor in ACS patients, while others have shown that smokers on clopidogrel have a better outcome than non smokers on clopidogrel …”

“…The reasons for this paradoxical effect of smoking are not completely known, but could be related to an induction of CYP1A2 by cigarette smoking, which would lead to an increased production of the active metabolite of clopidogrel. 35,36 However, the interaction of smoking in patients with ACS remains controversial, with recent studies having questioned the role of smoking as a positive prognostic factor in ACS patients, [37][38][39][40][41] while others have shown that smokers on clopidogrel have a better outcome than non smokers on clopidogrel. [42][43][44] In support of this hypothesis is the observation that this paradoxical effect of smoking is not present with prasugrel, which is associated with greater active metabolite exposure and pharmacodynamic effects than clopidogrel therapy, regardless of smoking status.…”

Effects of Smoking on Ischemic Stroke, Intracranial Hemorrhage, and Coronary Artery Events in Japanese Patients With Non-Valvular Atrial Fibrillation

“…Their effects were significant in the full-adjusted models with Cox regression analysis, supporting the concept that the confounding of younger patients may mask the true risk of smoking for promoting coronary atherosclerosis. Much evidence has clarified the adverse effects of smoking on atherosclerotic pathogenesis, including causing increases in systemic inflammation and oxidative stress, and consequent endothelial dysfunction 23) and thrombosis formation, 28) and therefore, we believe that the apparent paradoxical inverse association between smoking and acute coronary syndrome in our cohort and others 27) does not have any essential meaning for the prevention of coronary artery diseases. It should be emphasized that smoking is not encouraged by the apparent negative associations in our data in the total population.…”

“…The tendency of the relationship with smoking was opposite between these 2 events: the incidence of percutaneous coronary intervention was slightly higher in smokers than in non-smokers (13.7 versus 11.6 per 1000 person-years), whereas that of acute coronary syndrome was much lower in smokers than in non-smokers (1.5 versus 4.1 per 1000 person-years). Although the reasons for the discrepancy are unclear, such paradoxical evidence regarding acute coronary syndrome has been identified in non-AF subjects in another hospital-based cohort in Japan, 27) suggesting a younger age is a confounding factor and a possible enhanced effect of antiplatelet agents by cigarettes. 27) When we extracted patients ≥ 65 years old, the incidence of percutaneous coronary intervention was 1.5 times higher in current smokers and patients with a total tobacco amount ≥ 800 cigarette-years than in former smokers and patients with a total tobacco amount < 800 cigarette-years, respectively.…”

“…Although the reasons for the discrepancy are unclear, such paradoxical evidence regarding acute coronary syndrome has been identified in non-AF subjects in another hospital-based cohort in Japan, 27) suggesting a younger age is a confounding factor and a possible enhanced effect of antiplatelet agents by cigarettes. 27) When we extracted patients ≥ 65 years old, the incidence of percutaneous coronary intervention was 1.5 times higher in current smokers and patients with a total tobacco amount ≥ 800 cigarette-years than in former smokers and patients with a total tobacco amount < 800 cigarette-years, respectively. Their effects were significant in the full-adjusted models with Cox regression analysis, supporting the concept that the confounding of younger patients may mask the true risk of smoking for promoting coronary atherosclerosis.…”