july 2020 • NEJM

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

Johnston, S. Claiborne, Amarenco, Pierre, Denison, Hans, et al.

DOI: 10.1056/NEJMoa1916870

Content curated by:David Rodrigues

Key message

Será que em doentes com AVC isquémico não cardioembólico ou com AIT de elevado risco, com sintomas há menos de 24 horas, a associação ticagrelor + aspirina durante 30 dias quando comparada com apenas aspirina, reduz novo evento cerebrovascular ou mortalidade? Em doentes com AVC isquémico não cardioembólico ou AIT de elevado risco a dupla antiagregação com ticagrelor+AAS foi superior a AAS isolada na prevenção de novo evento cerebrovascular mas à custa de mais eventos hemorrágicos graves. O ensaio clínico foi bem conduzido. A aplicação destes resultados deve considerar tanto o risco cardiovascular como o risco hemorrágico de cada doente. Devemos ainda considerar outras opções concretamente clopidogrel+AAS ou AAS isoladamente (pelo menos esta).

Analysis

Population

Doentes com AVC isquémico não cardioembólico ou com AIT de elevado risco, com sintomas há menos de 24 horas, (60% tinha NIHSS ≤3)

Method

Ensaio clínico aleatorizado, dupla-ocultação, grupos bastante equiparados na baseline, apenas 1 doente perdido para follow-up. Análise ITT

Results

11.016 pacientes foram aleatorizados (5523 no grupo ticagrelor-aspirina e 5493 no grupo aspirina). Outcome primário ocorreu em 303 pacientes (5,5%) no grupo ticagrelor-aspirina e em 362 pacientes (6,6%) no grupo aspirina (Hazard Ratio de 0,83; intervalo de confiança de 95% [IC], 0,71 a 0,96; P = 0,02). AVC isquémico ocorreu em 276 pacientes (5,0%) no grupo ticagrelor-aspirina e em 345 pacientes (6,3%) no grupo aspirina (taxa de risco de 0,79; IC95%, 0,68 a 0,93; P = 0,004). A incidência de incapacidade não diferiu significativamente entre os dois grupos. Hemorragia grave ocorreu em 28 pacientes (0,5%) no grupo ticagrelor-aspirina e em 7 pacientes (0,1%) no grupo aspirina (P = 0,001).

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. opens in new tab.)