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Am Heart J. 2014 Jul;168(1):76-87.e1. doi: 10.1016/j.ahj.2014.04.011. Epub 2014 Apr 24.

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.

Author information

1
Medisch Centrum Alkmaar, Alkmaar, the Netherlands. Electronic address: j.h.cornel@mca.nl.
2
Duke Clinical Research Institute, Durham, NC; Division of Cardiology, Department of Medicine, Duke University Medical Center, Durham, NC.
3
Duke Clinical Research Institute, Durham, NC.
4
Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
5
Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
6
Daiichi Sankyo, London, United Kingdom.
7
Division of Cardiology, University of Alberta, Edmonton, Alberta, Canada.
8
Centre for Chronic Disease Control, New Delhi, India.
9
Auckland City Hospital, Green Lane Cardiovascular Service, Auckland, New Zealand.
10
Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, Scotland, United Kingdom.
11
Sinai Center for Thrombosis Research, Baltimore, MD.

Erratum in

  • Am Heart J. 2014 Oct;168(4):605.

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.

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.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT00699998.

PMID:
24952863
DOI:
10.1016/j.ahj.2014.04.011
[Indexed for MEDLINE]

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