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

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• 作者：Jan H. Cornel ; MD ; PhD^a ; ^{j.h.cornel@mca.nl" class="auth_mail} ; E. Magnus Ohman ; MB ; ChB^b ; ^c ; Benjamin Neely ; MS^b ; Peter Clemmensen ; MD^d ; Piyamitr Sritara ; MD^e ; Dmitry Zamoryakhin ; MD^f ; Paul W. Armstrong ; MD^g ; Dorairaj Prabhakaran ; MD ; DM ; MSc^h ; Harvey D. White ; MB ; ChB ; DScⁱ ; Keith A.A. Fox ; MB ; ChB^j ; Paul A. Gurbel ; MD^k ; Matthew T. Roe ; MD ; MHS^b ; ^c ; for the TRILOGY ACS Investigators
• 刊名：American Heart Journal
• 出版年：July 2014
• 年：2014
• 卷：168
• 期：1
• 页码：76-87.e1
• 全文大小：2192 K

文摘

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.