Effect of smoking status on clinical outcome and efficacy of clopidogrel in acute coronary syndrome

Background: The “smoker’s paradox” is an otherwise unexplained phenomenon in which the mortality of smokers after acute myocardial infarction is reduced, contrary to expectations. It has been suggested that an association with antiplatelet agents exists, but the true mechanism remains largely unidentified. Methods and Results: The analysis included 6,195 consecutive patients who underwent percutaneous coronary intervention (PCI) for acute coronary syndrome, registered in the Japanese multicenter PCI registry. Smokers were significantly younger and had less comorbidity than non-smokers. Unadjusted in-hospital mortality rate, general complication rate, and bleeding complication rate were lower in smokers than in non-smokers. After adjustment, the trend persisted and smoking was not associated with overall mortality (odds ratio [OR], 0.90; 95% confidence interval [CI]: 0.61–1.34; P=0.62), and was associated with lower overall (P=0.032) and bleeding complication events (P=0.040). Clopidogrel effectively reduced the occurrence of in-hospital complications and major adverse cardiac events in smokers compared with non-smokers (OR, 0.55; 95% CI: 0.53–0.98 vs. OR, 1.20; 95% CI: 0.87–1.67; and OR, 0.37; 95% CI: 0.20–0.70 vs. OR, 1.48; 95% CI: 0.90–2.43, respectively). Conclusions: The smoker’s paradox was largely explained by confounding factors related to the lower risk profile of smokers, and they benefited from a positive modification of the efficacy of clopidogrel.