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:
Dr. Cornel receives personal fees from AstraZeneca, Merck, Eli Lilly, and Bayer. Dr. Ohman receives grant funding and travel expenses from Daiichi Sankyo and Lilly; consulting fees from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead Sciences, Janssen Pharmaceuticals, Liposcience, Merck, Pozen, Roche, Sanofi-Aventis, The Medicines Company, and Web MD; grant funding from Gilead Sciences; and lecture fees from Gilead Sciences, Boehringer Ingelheim, and The Medicines Company. Mr. Neely has no conflicts of interest to disclose. Dr. Clemmensen receives grant support from Eli Lilly, Bayer, and The Medicines Company, and personal fees from Daiichi Sankyo, Eli Lilly, Bayer, The Medicines Company, Boehringer Ingelheim, and Pfizer/BMS. Dr. Sritara has no conflicts of interest to disclose. Dr. Zamoryakhin is an employee of Daiichi Sankyo. Dr. Armstrong receives consulting fees from Eli Lilly, Hoffman-La Roche, Regado Biosciences, Axio/Orexigen, Merck, and Bayer; grant funding from Boehringer Ingelheim, Merck, GlaxoSmithKline, Amylin, Sanofi-Aventis, and Regado; and payment for developing educational presentations from AstraZeneca. Dr. Prabhakaran reports receiving travel support and an honorarium from Eli Lilly; he also reports receiving grants from the Lilly Foundation and Medtronic Foundation. Dr. White receives grant funding from Sanofi-Aventis, Eli Lilly, The Medicines Company, the National Institutes of Health, Roche, Merck Sharp & Dohme, AstraZeneca, GlaxoSmithKline, and Daiichi Sankyo. Dr. Fox receives grant funding from Bayer/Johnson & Johnson, Janssen, Eli Lilly, and AstraZeneca, and personal fees from Bayer/Johnson & Johnson, Janssen, Lilly, AstraZeneca, and Sanofi-Aventis. Dr. Gurbel reports serving as a consultant for Daiichi Sankyo, Sankyo, Lilly, Pozen, Bayer, AstraZeneca, Accumetrics, Nanosphere, Sanofi-Aventis, Boehringer Ingelheim, Merck, Medtronic, CSL, and Haemonetics; receiving grants from the National Institutes of Health, Daiichi Sankyo, Lilly, Pozen CSL, AstraZeneca, Sanofi-Aventis, Haemoscope, Harvard Clinical Research Institute, and Duke Clinical Research Institute; receiving payment for lectures, including service on speakers' bureaus, from Lilly, Daiichi Sankyo, Nanosphere, and Merck; receiving payment for development of educational presentations from Merck, the Discovery Channel, and Pri-Med; holding stock or stock options in Merck, and Pfizer; and holding patents in the area of personalized antiplatelet therapy and interventional cardiology. Dr. Roe receives consulting fees from Bristol-Myers Squibb, GlaxoSmithKline, Merck, Janssen Pharmaceuticals, KAI Pharmaceuticals, Sanofi-Aventis, Helsinn Pharmaceuticals, Regeneron, Novartis, AstraZeneca, Orexigen, Eli Lilly, and Daiichi Sankyo; research grants from Bristol-Myers Squibb, Hoffman-La Roche, Novartis, Schering-Plough, KAI Pharmaceuticals, Eli Lilly, AstraZeneca, and Janssen Pharmaceuticals; and speakers’ bureau payments from AstraZeneca and Janssen.
Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
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
VL - 168
SP - 76-87.e1
JO - American Heart Journal
JF - American Heart Journal
SN - 0002-8703
IS - 1
ER -