Fewer subsequent strokes with ticagrelor plus aspirin than with aspirin alone

Reference

Johnston SC, Amarenco P, Denison H, et al, for the THALES Investigators. Ticagrelor and aspirin or aspirin alone in acute ischemic stroke or TIA. N Engl J Med 2020;383(3):207-217.

Synopsis

Although a previous study of ticagrelor did not show a benefit over aspirin in patients with acute ischemic stroke, the effect of ticagrelor plus aspirin is not known. Using concealed allocation, these investigators randomized patients with mild-to-moderate acute nonembolic ischemic strokes (National Institutes of Health Stroke Scale score < 5) or high-risk transient ischemic attacks to receive ticagrelor plus aspirin (n = 5523) or matching placebo plus aspirin (n = 5493). Patients receiving thrombolysis or thrombectomy and those who had intracranial bleeding were excluded. Ticagrelor (or matching placebo) was given at a loading dose of 180 mg, followed by a maintenance dose of 90 mg twice daily for 30 days. Aspirin was given at a loading dose of 300 mg to 325 mg, followed by a dose of 75 mg to 100 mg daily. The 2 groups were balanced at baseline: mean age was 65 years, 39% were women, and 91% presented with ischemic stroke. The primary outcome, a composite of subsequent stroke or death at 30 days, occurred less frequently in the ticagrelor plus aspirin group than in the aspirin-only group (5.5% vs 6.6%; hazard ratio [HR] 0.83; 95% CI 0.71 - 0.96; P = .02). The secondary outcome of subsequent strokes was decreased from 6.3% to 5.0% in the ticagrelor plus aspirin group (HR 0.79; 0.68 - 0.93; P = .004). Overall, disability at the end of the treatment period did not differ significantly between the 2 groups. Severe bleeding was rare but more frequent in the ticagrelor plus aspirin group (0.5% vs 0.1%; HR 3.99; 1.74 - 9.14; P =.001). Overall, 2.8% of patients in the ticagrelor plus aspirin group discontinued treatment because of bleeding (0.6% in the aspirin group).