Ticagrelor- vs Clopidogrel-Aspirin for Preventing New Stroke in Patients With Different Subtypes

Compared with clopidogrel-aspirin, ticagrelor-aspirin is effective and safe for preventing recurrent stroke.

The efficacy and safety of ticagrelor-aspirin compared with clopidogrel-aspirin for preventing new stroke are consistent among patients with different causes of previous stroke, according to a study in Stroke.

Researchers reported findings from a prespecified exploratory analysis of the CHANCE-2 trial.

Participants were aged 40 years or older, had minor stroke or high-risk transient ischemic attack, were able to receive the study drug within 24 hours of symptom onset, and carried CYP2C19 loss of function alleles. The patients were classified based on the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) classification as having large-artery atherosclerosis (LAA), cardioembolism, small-vessel occlusion (SVO), stroke of other cause, and stroke of undetermined etiology.

The participants were randomly assigned in a 1:1 ratio to ticagrelor-aspirin (placebo clopidogrel plus a 180-mg loading dose of ticagrelor on day 1 followed by 90 mg twice daily on days 2-90) or to clopidogrel-aspirin (placebo ticagrelor plus a 300-mg loading dose of clopidogrel on day 1 followed by 75 mg daily on days 2-90).

…the efficacy and safety of ticagrelor-aspirin vs clopidogrel-aspirin in preventing new stroke were similar in patients with different TOAST subtypes.

The primary outcome was a new ischemic or hemorrhagic stroke at 90 days, and the primary safety outcome was severe or moderate bleeding according to Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries criteria at 90 days.

The cohort included 6336 patients, 1696 (26.8%) with LAA, 1750 (27.6%) with SVO, and 2890 (45.6%) with stroke of undetermined etiology, who were enrolled from September 23, 2019, to March 22, 2021.

Patients with LAA had the highest 3-month risk for recurrent stroke (10.2%), followed by those with stroke of undetermined etiology (5.4%) and those with SVO (5.3%). Ticagrelor-aspirin and clopidogrel-aspirin had a comparable effect in patients with LAA (hazard ratio [HR], 0.86; 95% CI, 0.63-1.18; P =.34) and stroke of undetermined etiology (HR, 0.80; 95% CI, 0.58-1.10; P =.17). However, ticagrelor-aspirin was more effective vs clopidogrel-aspirin in patients with SVO (HR, 0.51; 95% CI, 0.33-0.79; P =.002), with P =.08 for treatment × TOAST subtype interaction effect. The findings were comparable for ischemic stroke and composite vascular events.

Participants who had a different cause in the ticagrelor-aspirin group and the clopidogrel-aspirin group had similar rates of severe or moderate bleeding (0.3% vs 0.1% in those with LAA; 0.6% vs 0.7% in those with SVO; and 0.1% vs 0.2% in those with stroke of undetermined etiology; P =.47 for the treatment × cause subtype interaction). Similar findings occurred regarding mortality.

Ticagrelor-aspirin was associated with a higher risk of any bleeding in patients with SVO and stroke of undetermined etiology vs clopidogrel-aspirin treatment, although the interaction effect was nonsignificant (P =.18 for the treatment × cause subtype interaction).

The use of ticagrelor-aspirin therapy did not significantly increase the bleeding risk in patients with LAA vs clopidogrel-aspirin treatment (HR, 1.59; 95% CI, 0.87-2.90; P =.13).

Among several study limitations, 12% of participants had incomplete cause evaluations, which may have introduced bias, and all patients in CHANCE-2 were Chinese and had a high prevalence of LAA. Also, the interaction test was not significant, and so the observed differences in efficacy among different causes could be due to chance.

“Consistent with the overall results of the CHANCE-2 intention-to-treat population, the efficacy and safety of ticagrelor-aspirin vs clopidogrel-aspirin in preventing new stroke were similar in patients with different TOAST subtypes,” wrote the investigators. “There was no significant treatment-by-TOAST classification interaction.”Disclosure: Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Xie X, Jing J, Meng X, et al.; on behalf of the  CHANCE-2 Investigators. Dual antiplatelet therapies and causes in minor stroke or transient ischemic attack: a prespecified analysis in the CHANCE-2 trial. Stroke. Published online August 7, 2023. doi: 10.1161/STROKEAHA.122.042233