Clinical Question

Is ticagrelor (Brilinta) plus aspirin superior to aspirin alone for decreasing the risk of subsequent stroke or death in patients with acute ischemic stroke?

Bottom Line

For patients with mild to moderate acute nonembolic ischemic stroke, treatment with ticagrelor plus aspirin for 30 days resulted in fewer subsequent strokes but similar overall disability and an increase in severe bleeding compared with aspirin alone (number needed to treat to prevent one event of the composite outcome of stroke or death = 92; number needed to harm to cause one episode of severe bleeding = 263). (Level of Evidence = 1b)

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, the investigators randomized patients with mild to moderate acute nonembolic ischemic strokes (National Institutes of Health Stroke Scale score less than 5) or high-risk transient ischemic attacks to receive ticagrelor plus aspirin (n = 5,523) or matching placebo plus aspirin (n = 5,493). 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 dosage of 90 mg twice daily for 30 days. Aspirin was given at a loading dose of 300 mg to 325 mg, followed by a dosage of 75 mg to 100 mg daily. The two 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 often 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 to 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; 95% CI, 0.68 to 0.93; P = .004). Disability at the end of the treatment period did not differ significantly between the two groups. Severe bleeding was rare but more common in the ticagrelor plus aspirin group (0.5% vs. 0.1%; HR = 3.99; 95% CI, 1.74 to 9.14; P = .001). In the ticagrelor plus aspirin group, 2.8% of patients discontinued treatment because of bleeding (vs. 0.6% in the aspirin-only group).

Study design: Randomized controlled trial (double-blinded)

Funding source: Industry

Allocation: Concealed

Setting: Inpatient (any location) with outpatient follow-up

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