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

Introduction Large-vessel occlusion (LVO) stroke represents around one-third of all ischemic strokes; moreover, patients with symptomatic intracranial or extracranial arterial stenosis are at increased risk of stroke occurrence and early stroke recurrence. Several trials have evaluated the potential role of ticagrelor in ischemic stroke, SOCRATES trial which 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. When cilostazol was compared with aspirin and ticlopidine, it showed a comparable ability to inhibit platelet reactivity and aggregation to that produced by ticlopidine and aspirin. Additionally, cilostazol was associated with fewer hemorrhagic side effects. In Egypt, the monthly cost of cilosatzol 100 mg Bid is approximately half that of ticagrelor 90 mg Bid, making it a potentially cost-effective antiplatelet agent, especially in a country experiencing an economic crisis. To the best of our knowledge, no such study that compared cilostazol versus ticagrelor in African patients with minor stroke or TIA, so we aimed to evaluate the benefits or hazards of adding cilostazol or ticagrelor to aspirin in patients with minor ischemic stroke or TIA to support the tailored use of cilostazol, which is a cheaper antiplatelet and has a lower risk of haemorrhagic complications. Methods We randomly enrolled 900 non-cardioembolic minor stroke or TIA patients to receive loading and maintenance doses of cilostazol and aspirin or ticagrelor and aspirin in a one-to-one ratio and followed them up for three months. Results Nine hundred patients were assigned, in a one-to-one ratio, to receive either cilostazol and aspirin or ticagrelor and aspirin; 857 patients completed the three-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, 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). Fifteen (3.3%) patients in the cilostazol group and twenty-eight (6.2%) patients in the ticagrelor group decided to stop treatment prematurely due to intolerable hemorrhagic and non-hemorrhagic adverse effects (HR 0.28; 95% CI, 0.16–0.57; P-value = 0.02). Conclusion Combining cilostazol with aspirin in Egyptian patients with non-cardioembolic minor ischemic stroke or TIA yielded reductions in the rates of recurrent stroke, MI, and death due to vascular events, which were comparable to the rates produced upon combining ticagrelor and aspirin; moreover, cilostazol and aspirin produced significantly lower rates of hemorrhagic complications and were more tolerable than ticagrelor and aspirin. Registration: ClinicalTrials.gov, NCT06591377, 09-08-2024.