N Engl J Med 2016 Jul 10;375(1):35-43. Epub 2016 May 10.
From the Dean's Office, Dell Medical School, University of Texas, Austin (S.C.J.); the Department of Neurology and Stroke Center, Bichat University Hospital and Medical School, Paris (P.A.); Stanford University Medical Center, Stanford Stroke Center, Palo Alto (G.W.A.), and the Department of Neurology, University of California, San Francisco, San Francisco (J.D.E.) - both in California; AstraZeneca, Gothenburg, Sweden (H.D., P.H., J.J.); the Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston (S.R.E.); the National Cerebral and Cardiovascular Center, Suita, Osaka, Japan (K.M.); the Stroke Unit, Hospital Vall d'Hebron, Barcelona (C.A.M.); the Department of Neurology, Tiantan Hospital, Beijing (Y.W.); and the Department of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong (K.S.L.W.).
Background: Ticagrelor may be a more effective antiplatelet therapy than aspirin for the prevention of recurrent stroke and cardiovascular events in patients with acute cerebral ischemia.
Methods: We conducted an international double-blind, controlled trial in 674 centers in 33 countries, in which 13,199 patients with a nonsevere ischemic stroke or high-risk transient ischemic attack who had not received intravenous or intraarterial thrombolysis and were not considered to have had a cardioembolic stroke were randomly assigned within 24 hours after symptom onset, in a 1:1 ratio, to receive either ticagrelor (180 mg loading dose on day 1 followed by 90 mg twice daily for days 2 through 90) or aspirin (300 mg on day 1 followed by 100 mg daily for days 2 through 90). The primary end point was the time to the occurrence of stroke, myocardial infarction, or death within 90 days.
Results: During the 90 days of treatment, a primary end-point event occurred in 442 of the 6589 patients (6.7%) treated with ticagrelor, versus 497 of the 6610 patients (7.5%) treated with aspirin (hazard ratio, 0.89; 95% confidence interval [CI], 0.78 to 1.01; P=0.07). Ischemic stroke occurred in 385 patients (5.8%) treated with ticagrelor and in 441 patients (6.7%) treated with aspirin (hazard ratio, 0.87; 95% CI, 0.76 to 1.00). Major bleeding occurred in 0.5% of patients treated with ticagrelor and in 0.6% of patients treated with aspirin, intracranial hemorrhage in 0.2% and 0.3%, respectively, and fatal bleeding in 0.1% and 0.1%.
Conclusions: In our trial involving patients with acute ischemic stroke or transient ischemic attack, ticagrelor was not found to be superior to aspirin in reducing the rate of stroke, myocardial infarction, or death at 90 days. (Funded by AstraZeneca; ClinicalTrials.gov number, NCT01994720.).