the CSPS.com Trial Investigators
To determine the optimal timing for initiating long-term dual medication of cilostazol with aspirin or clopidogrel after onset of stroke. Such dual therapy was proven to have a lower risk of ischemic stroke recurrence and a similar risk of bleeding compared to aspirin or clopidogrel alone in patients at high-risk for recurrent ischemic stroke in a randomized controlled trial (CSPS.com).
A sub-analysis of CSPS.com that randomly assigned 1879 patients between 8 and 180 days of high-risk non-cardioembolic ischemic stroke onset to receive aspirin or clopidogrel alone or a combination of cilostazol with aspirin or clopidogrel. Patients were divided into three groups according to the timing for initiation of trial treatment. The primary efficacy outcome was the first recurrence of ischemic stroke. Safety outcomes included severe or life-threatening bleeding.
There was a significant treatment-by-subgroup interaction for the primary efficacy outcome between trial treatment and trichotomized groups (P=0.002). The recurrence of ischemic stroke was less common with dual therapy than monotherapy in 467 patients initiating the treatment between 15 and 28 days of onset (aHR 0.34, 95% CI 0.12-0.95) and 914 patients initiating at ≥29 days (0.27, 0.12-0.63), and similarly common in 498 patients initiating within 14 days (1.02, 0.51-2.04). Severe or life-threatening bleeding occurred similarly between dual therapy and monotherapy in any trichotomized groups.
Long-term dual antiplatelet therapy using cilostazol was more effective for secondary stroke prevention than monotherapy in patients initiating the medication at 15 days or later.
ClinicalTrials.gov NCT01995370, UMIN Clinical Trials Registry 000012180