BACKGROUND: 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 1994 participants (28%) [corrected] 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.
American Heart Journal, 2014, Vol 168, Issue 1
Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't; Acute Coronary Syndrome; Aged; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Follow-Up Studies; Great Britain; Humans; Male; Middle Aged; Myocardial Revascularization; Piperazines; Platelet Aggregation Inhibitors; Prognosis; Purinergic P2Y Receptor Antagonists; Retrospective Studies; Smoking; Survival Rate; Thiophenes; Ticlopidine; Time Factors; Treatment Outcome; United States