BackgroundTrials 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.MethodsWe 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.ResultsA 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).ConclusionsAmong 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.)A trial involving 11,016 patients showed that the combination
of ticagrelor and aspirin after a stroke or high-risk transient ischemic attack was
better than aspirin alone in preventing a stroke or death within 30 days. Severe bleeding
was rare but occurred more frequently in the dual antiplatelet group.
