Abstract 13208: Time-Dependent Interactions of Prasugrel vs Clopidogrel on the Long-Term Risks of Stroke after Acute Coronary Syndromes: Results from the TRILOGY ACS Trial
Introduction: The role of more intense, sustained platelet inhibition in preventing post-ACS stroke is unclear. We previously observed a signal for a reduced risk of stroke in the TRILOGY ACS trial after 12 months of treatment with prasugrel vs clopidogrel in medically managed ACS patients.
Methods: We examined the TRILOGY efficacy population (7243 ACS patients <75 y), analyzing differences in baseline characteristics between patients with/without a stroke event through 30 months with a Cox proportional hazards model. Patients with prior stroke and/or need for chronic anticoagulation were excluded. We also assessed the impact of prasugrel vs clopidogrel on risk of all stroke events and ischemic stroke over time with an extended Cox proportional hazards model.
Results: There were few stroke events (n=77; ischemic stroke=62; hemorrhagic stroke=15) through 30 months. Patients with stroke were older, had more comorbidities including atrial fibrillation, and had a higher GRACE long-term mortality risk score vs those without stroke. As reported, there was a trend for a lower unadjusted frequency of all stroke events through 30 months for those treated with prasugrel vs clopidogrel: 31 (1.5%) vs 46 (2.2%); p=0.08. There was a significant treatment by time interaction for those with ischemic stroke (p=0.03) consistent with the 12-month landmarked Kaplan-Meier log-rank test showing a reduced hazard of ischemic stroke after 12 months in those taking prasugrel vs clopidogrel (p=0.04). No significant interactions between treatment effect of prasugrel vs clopidogrel and time were observed when all stroke events were analyzed.
Conclusions: Consistent with overall TRILOGY results, we observed a potential late treatment effect in medically managed ACS patients <75 y, suggesting that longer duration of more intense platelet inhibition may be associated with a lower risk of ischemic stroke after 12 months. These hypothesis-generating results merit study in larger populations.
Author Disclosures: C. Chin: Speakers Bureau; Modest; Astra Zeneca, Boston Scientific. Honoraria; Modest; Boston Scientific. B. Neely: None. E.M. Ohman: Research Grant; Significant; Daiichi Sankyo, Lilly, Gilead. Consultant/Advisory Board; Modest; AstraZeneca, Daiichi Sankyo, Lilly, Gilead, Pozen, The Medicines Company. Consultant/Advisory Board; Significant; WebMD, Abiomed, Janssen, Sanofi-Aventis. P.W. Armstrong: Research Grant; Significant; Boehringer Ingelheim, Merck Sharp & Dohme, GSK, Amylin, Merck, Sanofi-Aventis, Regado,. Consultant/Advisory Board; Modest; AstraZeneca, Boehringer Ingelheim, GSK, Merck, Axio/Orexigen, Lilly, Bayer. Consultant/Advisory Board; Significant; Hoffman-La Roche. H.D. White: Consultant/Advisory Board; Modest; Astra Zeneca; Merck Sharpe & Dohme; Roche; Regado Biosciences. Research Grant; Significant; Sanofi Aventis; Eli Lilly; Medicines Company; NIH; Roche; Merck Sharpe & Dohme; Astra Zeneca; GSK; Daiichi Sankyo Pharma Development. D. Prabhakaran: Consultant/Advisory Board; Significant; Lilly. K.A. Fox: Research Grant; Significant; AstraZeneca, British Heart Foundation. K.J. Winters: Employment; Significant; Lilly. Ownership Interest; Modest; Lilly. M.T. Roe: Research Grant; Significant; Lilly, Sanofi-Aventis, Daiichi Sankyo, Amgen, Familial Hypercholesterolemia Foundation. Consultant/Advisory Board; Modest; Lilly, Janssen, Elsevier. Consultant/Advisory Board; Significant; AstraZeneca, Merck, Amgen. Other; Modest; AstraZeneca, BMS.
- © 2014 by American Heart Association, Inc.