Ticagrelor and Aspirin or Aspirin Alone in Acute Ischemic Stroke or TIA

N Engl J Med. 2020 Jul 16;383(3):207-217. doi: 10.1056/NEJMoa1916870.

Abstract

Background: Trials have evaluated the use of clopidogrel and aspirin to prevent stroke after an ischemic stroke or transient ischemic attack (TIA). In a previous trial, ticagrelor was not better than aspirin in preventing vascular events or death after stroke or TIA. The effect of the combination of ticagrelor and aspirin on prevention of stroke has not been well studied.

Methods: We conducted a randomized, placebo-controlled, double-blind trial involving patients who had had a mild-to-moderate acute noncardioembolic ischemic stroke, with a National Institutes of Health Stroke Scale (NIHSS) score of 5 or less (range, 0 to 42, with higher scores indicating more severe stroke), or TIA and who were not undergoing thrombolysis or thrombectomy. The patients were assigned within 24 hours after symptom onset, in a 1:1 ratio, to receive a 30-day regimen of either ticagrelor (180-mg loading dose followed by 90 mg twice daily) plus aspirin (300 to 325 mg on the first day followed by 75 to 100 mg daily) or matching placebo plus aspirin. The primary outcome was a composite of stroke or death within 30 days. Secondary outcomes were first subsequent ischemic stroke and the incidence of disability within 30 days. The primary safety outcome was severe bleeding.

Results: A total of 11,016 patients underwent randomization (5523 in the ticagrelor-aspirin group and 5493 in the aspirin group). A primary-outcome event occurred in 303 patients (5.5%) in the ticagrelor-aspirin group and in 362 patients (6.6%) in the aspirin group (hazard ratio, 0.83; 95% confidence interval [CI], 0.71 to 0.96; P = 0.02). Ischemic stroke occurred in 276 patients (5.0%) in the ticagrelor-aspirin group and in 345 patients (6.3%) in the aspirin group (hazard ratio, 0.79; 95% CI, 0.68 to 0.93; P = 0.004). The incidence of disability did not differ significantly between the two groups. Severe bleeding occurred in 28 patients (0.5%) in the ticagrelor-aspirin group and in 7 patients (0.1%) in the aspirin group (P = 0.001).

Conclusions: Among patients with a mild-to-moderate acute noncardioembolic ischemic stroke (NIHSS score ≤5) or TIA who were not undergoing intravenous or endovascular thrombolysis, the risk of the composite of stroke or death within 30 days was lower with ticagrelor-aspirin than with aspirin alone, but the incidence of disability did not differ significantly between the two groups. Severe bleeding was more frequent with ticagrelor. (Funded by AstraZeneca; THALES ClinicalTrial.gov number, NCT03354429.).

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aspirin / adverse effects
  • Aspirin / therapeutic use*
  • Disability Evaluation
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Hemorrhage / chemically induced
  • Humans
  • Ischemic Attack, Transient / complications
  • Ischemic Attack, Transient / drug therapy*
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Platelet Aggregation Inhibitors / adverse effects
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Purinergic P2Y Receptor Antagonists / therapeutic use
  • Secondary Prevention
  • Stroke / complications
  • Stroke / drug therapy*
  • Stroke / mortality
  • Stroke / prevention & control
  • Ticagrelor / adverse effects
  • Ticagrelor / therapeutic use*

Substances

  • Platelet Aggregation Inhibitors
  • Purinergic P2Y Receptor Antagonists
  • Ticagrelor
  • Aspirin

Associated data

  • ClinicalTrials.gov/NCT03354429