Abstract 18205: Rivaroxaban and Improved Modified Rankin Scale Score Among Patients With Acute Coronary Syndrome who Experience Stroke - Insights From the ATLAS ACS-2-TIMI-51 Clinical Trial
Introduction: Factor X-mediated thrombin overproduction following a stroke may contribute to central nervous system injury and neurological disability. Thrombin induces a dose-dependent apoptotic response in neurons and may increase the risk of re-thrombosis. In ATLAS ACS-2-TIMI-51, we evaluated the effects of the Xa inhibitor, rivaroxaban, on neurological outcomes in ACS patients who experienced a stroke.
Methods: ATLAS ACS-2-TIMI-51 was a double-blind, placebo-controlled, phase 3 trial that randomized ACS patients to either 2.5 mg rivaroxaban bid, 5 mg rivaroxaban bid, or placebo with standard-of-care antiplatelet therapy for a mean of 13.1 months and up to 31 months (n=15,526). All stroke events were adjudicated by an independent, blinded clinical events committee.
Results: A total of 128 stroke events with investigator-reported Modified Rankin Scale Score (mRS score) were identified, of which 69.5% (n=89) were ischemic, 26.6% (n=34) were hemorrhagic, and 3.9% (n=5) were of uncertain cause. Among all stroke types, fewer subjects experienced a disabling or fatal outcome (mRS score 3 to 6) in the rivaroxaban 2.5 mg bid group vs. the placebo group (17.1% (7/41) vs. 52.6% (20/38), p=0.001). When the analysis was confined to ischemic stroke, rivaroxaban 2.5 mg bid was associated with significantly fewer disabling or fatal ischemic strokes (3.9% (1/26) vs. 48.4% (15/31), p<0.001). A similar trend was observed with hemorrhagic stroke, but this association was not statistically significant (38.5% (5/13) vs. 80.0% (4/5), p=0.29). In a logistic regression model adjusting for imbalances in age, antiplatelet stratum (DAPT vs. aspirin monotherapy) and stroke type, patients receiving rivaroxaban 2.5 mg bid were 9 times less likely to experience a disabling or fatal outcome as compared with placebo (p=0.002). No differences were observed between rivaroxaban 5 mg bid and placebo.
Conclusions: Among ACS patients who experience a stroke, the addition of rivaroxaban 2.5 mg bid to standard-of-care antiplatelet therapy is associated with improved neurological outcomes.
Author Disclosures: Y. Daaboul: None. S. Korjian: None. J.L. Mega: Research Grant; Significant; AstraZeneca, Bayer Corp, BMS, Daiichi Sankyo, Eli Lilly, Janssen Inc, Sanofi. Consultant/Advisory Board; Modest; American Genomics, AstraZeneca, Bayer Corp, Janssen Inc, Portola Pharmaceuticals. A.N. Plotnikov: Employment; Significant; Johnson and Johnson. P. Burton: Employment; Significant; Johnson and Johnson. E. Braunwald: Research Grant; Modest; AstraZeneca, Merck & Co, GSK, Bristol-Myers Squibb, Beckman Coulter, Roche Diagnostics, Pfizer, Sanofi, Johnson & Johnson. Research Grant; Significant; Daiichi Sankyo. Speakers Bureau; Modest; Uncompensated lectures for Merck and CVRx. Consultant/Advisory Board; Modest; Merck (unpaid consultant). Other; Modest; Lecture fees from Eli Lilly, Menarini, Medscape, and Bayer HealthCare. Consulting fees from Sanofi, Genzyme, Amorcyte, the Medicines Company, and Cardiorentis. C.M. Gibson: Research Grant; Significant; Angel Medical Corporation, Bayer Corp, CSL Behring, Ikaria, Inc, Janssen Pharmaceuticals, Inc, Johnson & Johnson Corp, Portola Pharmaceuticals, Stealth BioTherapeutics, St. Jude’s Medical. Other Research Support; Modest; The Medicines Company. Honoraria; Modest; Boston Clinical Research Institute, Cardiovascular Research Foundation, Eli Lilly and Company, Gilead Sciences, Inc, Novo Nordisk Inc, Pfizer, St. Jude Medical Corp, The Medicines Company, WebMD.
- © 2016 by American Heart Association, Inc.