Ticagrelor plus aspirin versus cilostazol plus aspirin in the acute-phase treatment of large-vessel minor stroke or TIA: A randomized controlled multi-center trial, the TACTIS trial

Abstract

Introduction: More intensive antiplatelet agents may reduce recurrent stroke risk in minor stroke and TIA, particularly those with non-cardioembolic stroke. The SOCRATES trial showed that ticagrelor was not superior to aspirin in decreasing the risk of stroke, heart attack, or death at 90 days in patients with minor ischemic stroke or TIA. Cilostazol has been shown to have similar effects on platelet reactivity and aggregation to those produced by ticlopidine and aspirin, but may be associated with fewer hemorrhagic side effects. It is also cheaper than ticagrelor; for example, it is approximately half that of ticagrelor, making it a potentially cost-effective antiplatelet agent, especially in low and middle-income countries. Aim: To evaluate the benefits or hazards of adding cilostazol or ticagrelor to aspirin in patients with minor ischemic stroke or TIA. Methods: We randomized 900 first-ever, large-vessel occlusion minor ischemic stroke or TIA patients in a one-to-one ratio to receive either a 200 mg loading dose of cilostazol within 24 h after acute stroke symptoms, then 100 mg twice daily until day 90 post-stroke, or a 180 mg loading dose of ticagrelor during the first 24 h, followed by 90 mg twice daily from day 2 to day 90. Both groups received an open-label 300 mg loading dose of aspirin during the first 24 h, then 75 mg once daily. We followed up with our patients for 3 months. Results: 857 patients completed the 3-month follow-up study 34 (7.6%) patients in the cilostazol group and 29 (6.4%) patients in the ticagrelor group experienced a new stroke (either hemorrhagic or ischemic) (HR 1.37; 95% CI, 0.84–2.26; p -value = 0.21), and 44 (9.8%) patients in the cilostazol group and 40 (8.9%) patients in the ticagrelor group experienced a composite of a new stroke, myocardial infarction (MI), or death due to vascular insults (HR 1.11; 95% CI, 0.64–1.93; p -value = 0.30). Fifteen (3.3%) patients in the cilostazol arm and 30 (6.7%) patients in the ticagrelor arm experienced drug-related hemorrhagic complications (HR 0.32; 95% CI, 0.19–0.68; p -value = 0.01). Conclusion: Combining cilostazol with aspirin in large-vessel occlusion minor ischemic stroke or TIA was as effective as ticagrelor and aspirin in preventing recurrent stroke, MI, and death due to vascular events, but resulted in significantly lower rates of hemorrhagic complications.