TY - JOUR
T1 - Impact of smoking status on platelet function and clinical outcomes with prasugrel vs. clopidogrel in patients with acute coronary syndromes managed without revascularization
T2 - Insights from the TRILOGY ACS trial
AU - Cornel, Jan H.
AU - Ohman, E. Magnus
AU - Neely, Benjamin
AU - Clemmensen, Peter
AU - Sritara, Piyamitr
AU - Zamoryakhin, Dmitry
AU - Armstrong, Paul W.
AU - Prabhakaran, Dorairaj
AU - White, Harvey D.
AU - Fox, Keith A.A.
AU - Gurbel, Paul A.
AU - Roe, Matthew T.
N1 - Funding Information:
All statistical tests were performed at a significance level of 0.05. All analyses were conducted independently at the Duke Clinical Research Institute, Durham, North Carolina using SAS 9.3 (SAS Institute, Inc.) and R 3.0.0 ( http://www.r-project.org/ ). The TRILOGY ACS study was funded by an unrestricted research grant from Daiichi Sankyo and Eli Lilly and Co. Study sponsors had no role in the conception and design of this study or in creating the first draft of the manuscript. An employee of Daiichi Sankyo (Dr. Zamoryakhin) participated as an author during subsequent drafts of the manuscript. The authors are solely responsible for the design and conduct of this study, all study analyses, and the drafting and editing of the paper and its final contents.
Funding Information:
Source of funding: The TRILOGY ACS study was funded by Daiichi Sankyo and Eli Lilly.
PY - 2014/7
Y1 - 2014/7
N2 - 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 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.
AB - 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 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.
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U2 - 10.1016/j.ahj.2014.04.011
DO - 10.1016/j.ahj.2014.04.011
M3 - Article
C2 - 24952863
AN - SCOPUS:84903130512
SN - 0002-8703
VL - 168
SP - 76-87.e1
JO - American heart journal
JF - American heart journal
IS - 1
ER -