Time Course for Benefit and Risk of Ticagrelor and Aspirin in Acute Ischemic Stroke or Transient Ischemic Attack
OBJECTIVES: To investigate the short-term time course benefit and risk of ticagrelor with aspirin in acute mild-moderate ischemic stroke or high-risk transient ischemic attack (TIA) in the THALES (The Acute Stroke or Transient Ischemic Attack Treated with Ticagrelor and ASA for Prevention of Stroke and Death) trial. METHODS: In an exploratory analysis of the THALES trial, we evaluated the cumulative incidence of irreversible efficacy and safety outcomes at different timepoints during the 30-day treatment period. The efficacy outcome was major ischemic events defined as a composite of ischemic stroke or non-hemorrhagic death. The safety outcome was major hemorrhage defined as a composite of intracranial hemorrhage and fatal bleedings. Net clinical impact was defined as the combination of these two endpoints. RESULTS: This analysis included a total of 11,016 patients (5523 in the ticagrelor-aspirin group and 5493 in the aspirin group) with mean age of 65 years, and 39% were women. The reduction of major ischemic events by ticagrelor occurred in the first week (4.1% vs 5.3%; absolute risk reduction 1.15%, 95% CI 0.36% to 1.94%), and remained throughout the 30-day treatment period. An increase in major hemorrhage was seen during the first week and remained relatively constant in the following weeks (absolute risk increase, approximately 0.3%). Cumulative analysis showed that the net clinical impact favored ticagrelor-aspirin in the first week (absolute risk reduction 0.97%, 95% CI, 0.17% to 1.77%) and remained constant throughout the 30 days. DISCUSSION: In patients with mild-moderate ischemic stroke or high-risk TIA, the treatment effect of ticagrelor-aspirin was present from the first week. The ischemic benefit of ticagrelor-aspirin outweighs the risk of major hemorrhage throughout the treatment period, which may support the use of 30 days treatment with ticagrelor and aspirin in these patients. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for patients with mild-moderate ischemic stroke or high-risk TIA, the ischemic benefit of ticagrelor-aspirin outweighs the risk of major hemorrhage throughout the 30-day treatment period.
Wang, Yongjun; Pan, Yuesong; Li, Hao; Amarenco, Pierre; Denison, Hans; Evans, Scott R.; Himmelmann, Anders; James, Stefan; Knutsson, Mikael; Ladenvall, Per; Molina, Carlos A.; and Johnston, S Claiborne, "Time Course for Benefit and Risk of Ticagrelor and Aspirin in Acute Ischemic Stroke or Transient Ischemic Attack" (2022). GW Authored Works. Paper 783.
Biostatistics and Bioinformatics