title: Impact of smoking status on platelet function and clinical outcomes with prasugrel vs. clopidogrel in patients with acute coronary syndromes managed without revascularization: Insights from the TRILOGY ACS trial.
abstract: 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.
  
  
  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.
authors: Medisch Centrum Alkmaar, Alkmaar, the Netherlands. Electronic address: j.h.cornel@mca.nl.
authors: Jan H
authors: JH
authors: Cornel
authors: Duke Clinical Research Institute, Durham, NC; Division of Cardiology, Department of Medicine, Duke University Medical Center, Durham, NC.
authors: E Magnus
authors: EM
authors: Ohman
authors: Duke Clinical Research Institute, Durham, NC.
authors: Benjamin
authors: B
authors: Neely
authors: Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors: Peter
authors: P
authors: Clemmensen
authors: Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
authors: Piyamitr
authors: P
authors: Sritara
authors: Daiichi Sankyo, London, United Kingdom.
authors: Dmitry
authors: D
authors: Zamoryakhin
authors: Division of Cardiology, University of Alberta, Edmonton, Alberta, Canada.
authors: Paul W
authors: PW
authors: Armstrong
authors: Centre for Chronic Disease Control, New Delhi, India.
authors: Dorairaj
authors: D
authors: Prabhakaran
authors: Auckland City Hospital, Green Lane Cardiovascular Service, Auckland, New Zealand.
authors: Harvey D
authors: HD
authors: White
authors: Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, Scotland, United Kingdom.
authors: Keith A A
authors: KA
authors: Fox
authors: Sinai Center for Thrombosis Research, Baltimore, MD.
authors: Paul A
authors: PA
authors: Gurbel
authors: Duke Clinical Research Institute, Durham, NC; Division of Cardiology, Department of Medicine, Duke University Medical Center, Durham, NC.
authors: Matthew T
authors: MT
authors: Roe
mesh_terms: D054058:Acute Coronary Syndrome / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D000368:Aged; D000077144:Clopidogrel; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009204:Myocardial Revascularization; D010879:Piperazines / Q000008:administration & dosage*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage; D000068799:Prasugrel Hydrochloride; D011379:Prognosis; D058921:Purinergic P2Y Receptor Antagonists / Q000008:administration & dosage; D012189:Retrospective Studies; D012907:Smoking / Q000009:adverse effects* / Q000401:mortality; D015996:Survival Rate / Q000639:trends; D013876:Thiophenes / Q000008:administration & dosage*; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D013997:Time Factors; D016896:Treatment Outcome; D006113:United Kingdom / Q000453:epidemiology; D014481:United States / Q000453:epidemiology
chemical_list: D010879:Piperazines; D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D013876:Thiophenes; D000077144:Clopidogrel; D000068799:Prasugrel Hydrochloride; D013988:Ticlopidine