Jan H. CornelE. Magnus OhmanBenjamin NeelyPeter ClemmensenPiyamitr SritaraDmitry ZamoryakhinPaul W. ArmstrongDorairaj PrabhakaranHarvey D. WhiteKeith A.A. FoxPaul A. GurbelMatthew T. RoeAlkmaar Medical CentreDuke Clinical Research InstituteDuke University Medical CenterKobenhavns UniversitetMahidol UniversityDaiichi Sankyo Development LtdUniversity of AlbertaCentre for Chronic Disease ControlAuckland City HospitalUniversity of EdinburghSinai Center for Thrombosis Research2018-11-092018-11-092014-01-01American Heart Journal. Vol.168, No.1 (2014)10976744000287032-s2.0-84903130512https://repository.li.mahidol.ac.th/handle/20.500.14594/34837Background To further explore the impact of smoking on antiplatelet activity and treatment response, we evaluated time-dependent relationships between smoking status with on-treatment platelet reactivity and clinical outcomes for prasugrel vs. clopidogrel in patients with acute coronary syndromes managed medically without revascularization. Methods and Results A total of 7062 patients aged <75 years from the primary TRILOGY ACS cohort randomized to prasugrel vs. clopidogrel were evaluated through 30 months by baseline and time-dependent smoking status with adjusted proportional-hazards models. A total of 1613 participants (23%) were included in a platelet function sub-study evaluating serial P2Y12 reaction unit (PRU) measurements. Current smokers (n = 1566 [22%]) at baseline had fewer comorbidities compared with non-smokers; nearly half quit smoking during follow-up. Although median on-treatment PRU values were lower with prasugrel vs. clopidogrel, persistent smokers had lower serial PRU values in both treatment groups compared with non-smokers, with no differential interaction of treatment response by smoking status. The frequency of cardiovascular death, myocardial infarction, or stroke in current smokers was significantly lower with prasugrel (11.7%) vs. clopidogrel (18.6%), but there was no difference in non-smokers (13.8% vs. 13.7%), with significant interaction between treatment and baseline smoking status (P =.0002). Bleeding events occurred more frequently in prasugrel-treated patients with no significant interaction between treatment and baseline smoking status. Conclusions Among medically managed ACS patients <75 years of age, the risk of ischemic outcomes was significantly reduced with prasugrel vs. clopidogrel among smokers vs. non-smokers. No interaction between on-treatment platelet reactivity and smoking status was found. © 2014 Mosby, Inc.Mahidol UniversityMedicineArticleSCOPUS10.1016/j.ahj.2014.04.011