Ticagrelor-Aspirin Treatment Benefit vs Major Hemorrhage Risk in Stroke

Hemorrhagic stroke, 3D illustration showing hemorrhage on the brain surface and closeup view of the bleeding from a brain blood vessel
Researchers sought to assess the short-term benefit and risk of ticagrelor with aspirin in patients with acute mild-moderate ischemic stroke or high-risk transient ischemic attack.

Treatment up to 30 days with ticagrelor-aspirin was beneficial in patients with high-risk transient ischemic stroke (TIA) or mild-moderate ischemic stroke, reducing the risk for additional events and outweighing the possibility of major hemorrhage, according to study findings published in Neurology.

Up to 9% of patients with TIA or minor ischemic stroke have a repeat event within 3 months of their initial attack. Dual antiplatelet therapy (DAPT) carries additional risk of major hemorrhage, which may also be the case with ticagrelor plus aspirin. Researchers in the current study explored the short-term risk/benefit of ticagrelor with aspirin in high-risk TIA and in mild-moderate ischemic stroke. The primary outcome was ischemic stroke or death (not caused by bleeding) for efficacy, and bleeding in the brain or fatal bleeding for safety.

The researchers conducted an exploratory analysis of the THALES (The Acute Stroke or Transient Ischemic Attack Treated with Ticagrelor and ASA for Prevention of Stroke and Death) trial that included 5523 patients in the ticagrelor-aspirin cohort and 5493 patients in the aspirin/placebo cohort. The cohorts were balanced for age (65), female (39%), White (54%), Asian (43%), non-Hispanic or Latino (91%), body mass index interquartile range (23-29), current smokers (27%), hypertension (77%), diabetes mellitus (28%), previous ischemic stroke (16%), and previous TIA (5%).

Most of the reduction in major ischemic events related to ticagrelor were achieved in week 1 and maintained throughout the full 30-day treatment (4.1% vs 5.3%; absolute risk reduction 1.15%; 95% CI, 0.36%-1.94%). A total of 355 patients experienced an additional event in the placebo cohort within 30 days vs 291 patients in the ticagrelor cohort experienced an additional event within 30 days.

Major bleeding also increased though at a lower absolute rate of about 0.3% through the treatment period. The net impact derived from cumulative analysis showed ticagrelor-aspirin is more beneficial over placebo throughout treatment, and most significant in week 1 of treatment (absolute risk reduction 0.97%; 95% CI, 0.17%-1.77%).

Study limitations included not exploring the stoppage of treatment in less than 30 days, underpowered analysis for bleeding events, discontinuation of treatment bias, and lack of heterogeneity in racial/ethnic background.

Researchers concluded that “… the ischemic benefit of ticagrelor-aspirin treatment outweighs the risk of major hemorrhage throughout the 30-day treatment period in patients with mild-moderate ischemic stroke or high-risk TIA,” and while the benefit continues through the treatment period, most of the benefit occurs in the first week.

The study does not support the shortening of the 30-day regimen of DAPT with ticagrelor and aspirin, the researchers acknowledged.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

The study is supported by AstraZeneca.


Wang Y, Pan Y, Li H, et al. Time course for benefit and risk of ticagrelor and aspirin in acute ischemic stroke or transient ischemic attack. Neurology. Published online April 18, 2022. doi: 10.1212/WNL.0000000000200355