Ticagrelor Added to Aspirin in Acute Ischemic Stroke or Transient Ischemic Attack in Prevention of Disabling Stroke

Abstract

IMPORTANCE Reduction of subsequent disabling stroke is the main goal of preventive treatment in the acute setting after transient ischemic attack (TIA) or minor ischemic stroke. OBJECTIVE To evaluate the superiority of ticagrelor added to aspirin in preventing disabling stroke and to understand the factors associated with recurrent disabling stroke. DESIGN, SETTING, AND PARTICIPANTS The Acute Stroke or Transient Ischemic Attack Treated With Ticagrelor and Aspirin for Prevention of Stroke and Death (THALES) was a randomized clinical trial conducted between January 22, 2018, and December 13, 2019, with a 30-day follow-up, at 414 hospitals in 28 countries. The trial included 11 016 patients with a noncardioembolic, nonsevere ischemic stroke or high-risk TIA, including 10 803 with modified Rankin Scale score (mRS) recorded at 30 days. INTERVENTIONS Ticagrelor (180-mg loading dose on day 1 followed by 90 mg twice daily for days 2-30) or placebo within 24 hours of symptom onset. All patients received aspirin, 300 to 325 mg on day 1 followed by 75 to 100 mg daily for days 2 to 30. MAIN OUTCOMES AND MEASURES Time to the occurrence of disabling stroke (progression of index event or new stroke) or death within 30 days, as measured by mRS at day 30. Disabling stroke was defined by mRS greater than 1. RESULTS Among participants with 30-day mRS greater than 1, mean age was 68.1 years, 1098 were female (42.6%), and 2670 had an ischemic stroke (95.8%) as a qualifying event. Among 11 016 patients, a primary end point with mRS greater than 1 at 30 days occurred in 221 of 5511 patients (4.0%) randomized to ticagrelor and in 260 of 5478 patients (4.7%) randomized to placebo (hazard ratio [HR], 0.83; 95% CI, 0.69-0.99, P = .04). A primary end point with mRS 0 or 1 at 30 days occurred in 70 of 5511 patients (1.3%) and 87 of 5478 patients (1.6%) (HR, 0.79; 95% CI, 0.57-1.08; P = .14). The ordinal analysis of mRS in patients with recurrent stroke showed a shift of the disability burden following a recurrent ischemic stroke in favor of ticagrelor (odds ratio, 0.77; 95% CI, 0.65-0.91; P = .002). Factors associated with disability were baseline National Institutes of Health Stroke Scale score 4 to 5, ipsilateral stenosis of at least 30%, Asian race/ethnicity, older age, and higher systolic blood pressure, while treatment with ticagrelor was associated with less disability. CONCLUSIONS AND RELEVANCE In patients with TIA and minor ischemic stroke, ticagrelor added to aspirin was superior to aspirin alone in preventing disabling stroke or death at 30 days and reduced the total burden of disability owing to ischemic stroke recurrence. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT03354429

Antiplatelet Therapy in the Secondary Prevention of Non-cardioembolic Ischemic Stroke and Transient Ischemic Attack: A Mini-Review

“…The key findings reveal that DAPT appears to be safe and efficient in decreasing the risk of multiple ischemic strokes, particularly in the long term and with larger sample sizes ( 27 ), as well as being more effective than monotherapy in the early stages of acute ischemic stroke ( 24 ). This has also been confirmed by the most recent study by Amarenco et al ( 26 ), in which patients with TIA and minor ischemic stroke received ticagrelor in combination with aspirin to prevent disabling stroke or death at 30 days. The results showed that DAPT was more efficient than aspirin alone in decreasing the total burden of disability due to ischemic stroke recurrence.…”

“…Dual therapy: aspirin plus ticagrelor—Amarenco et al ( 26 ) evaluated the combination of ticagrelor and aspirin (as opposed to aspirin alone) in stroke prevention. The main endpoint was the time to stroke (progression of the event or a new stroke) or death within 30 days.…”

Contemporary antiplatelet therapy for secondary stroke prevention: a narrative review of current literature and guidelines

“…There were significant lower rates of stroke or death (5.5% vs 6.6%, HR, 0.83; 95% CI 0.71 to 0.96; p=0.02) and ischaemic stroke (5.0% vs 6.3%, HR, 0.79; 95% CI, 0.68 to 0.93; p=0.004), but higher rate of severe bleeding (0.5% vs 0.1%, p=0.001) in the DAPT group. Exploratory analysis showed that ticagrelor plus aspirin was associated with lower rate of disabling stroke or death than aspirin alone (4.0% vs 4.7%, p=0.001) 36. For every 1000 patients, DAPT would prevent 11 strokes or deaths at the cost of four severe haemorrhages.…”

Prevalence and Effect of Cerebral Small Vessel Disease in Stroke Patients With Aspirin Treatment Failure–A Hospital-Based Stroke Secondary Prevention Registry

“…In ischemic stroke with ATF, treatment with ticagrelor could reduce the risk of recurrent ischemic stroke, but increase combination of major or minor bleedings (40). However, combination of ticagrelor and aspirin does not decrease the incidence of composite of stroke or death and disabling stroke compared with aspirin after ischemic stroke with ATF (41,42).…”