Background: In the SOCRATES study (NCT01994720), addition of ticagrelor to patients on aspirin treatment before randomization may confer the effect of dual antiplatelet therapy as the antiplatelet effect of aspirin persists for more than a week. We aimed to explore safety and efficacy of ticagrelor in this pre-specified group of patients who had received aspirin prior to randomization.
Methods: We randomized 13,199 patients with a non-cardioembolic, non-severe ischemic stroke or high-risk transient ischemic attack (TIA) to ticagrelor (180mg loading dose on day 1 followed by 90mg twice daily for days 2-90) or aspirin (300mg on day 1 followed by 100mg daily for days 2-90) within 24 hours of symptom onset. The prior aspirin group consisted of patients who had received aspirin within 7 days before randomization. The primary endpoint was the time to the occurrence of stroke, myocardial infarction, or death within 90 days.
Results: The 4,232 patients with prior aspirin usage were older, had more vascular risk factors and vascular disease than the 8,967 patients with no prior aspirin usage. In the prior aspirin group, a primary endpoint occurred in 138/2,130 (6.5%) patients randomized to ticagrelor and in 177/2,102 (8.3%) patients randomized to aspirin (HR 0.76; 95% CI, 0.61-0.95, P=0.016) while for the non-aspirin group in 304/4,459 (6.9%) patients randomized to ticagrelor and in 320/4,508 (7.1%) patients randomized to aspirin (HR 0.96; 95%CI, 0.82-1.12, P=0.59). There was no significant treatment-by-prior-aspirin interaction (P=0.098). Major bleeding occurred in 0.7% of patients randomized to ticagrelor and in 0.4% randomized to aspirin (HR 1.58; 95% CI 0.68-3.65, P=0.28) in the prior aspirin group.
Conclusion: In this pre-specified exploratory analysis, ticagrelor showed a numerically greater treatment effect over aspirin in patients taking prior aspirin, although the interaction for treatment by prior aspirin was not statistically significant. Further study is needed to evaluate the combination of ticagrelor and aspirin in patients with minor stroke/TIA.