Advancing Secondary Stroke Prevention Strategies Optimal Timing of Dual Antiplatelet Therapy With Cilostazol

In this issue of Neurology (R), Toyoda et al.(1) describe an association between the poststroke timing of initiation of long-term cilostazol-based dual antiplatelet therapy (cDAPT), specifically cilostazol with aspirin or clopidogrel, and recurrent stroke, based on a subgroup analysis of the Cilostazol Stroke Prevention Study for Antiplatelet Combination ().(2) Whereas the original findings of demonstrated a lower risk of recurrent stroke in patients taking long-term cDAPT compared with those taking aspirin or clopidogrel monotherapy, questions remained regarding the optimal timing of starting the cDAPT regimen. In this post hoc subgroup analysis,(1) the authors divided the original 1879 participants into 3 subgroups (trial intervention started at 8-14 days, 15-28 days, and 29-180 days after noncardioembolic stroke) and found that stroke recurrence among those on cDAPT was significantly lower in the 15-28 days group and the 29-180 days group compared to aspirin or clopidogrel monotherapy, but not in those starting cDAPT between 8 and 14 days after stroke. Effect sizes for the cDAPT secondary stroke risk reduction were substantial, with an adjusted hazard ratio of 0.34 in the 15-28 days group (95% CI 0.12-0.95) and 0.27 in the 29-180 days group (95% CI 0.12-0.63).(1) When data from the 3 groups were combined, the risk of recurrent stroke in the cDAPT vs monotherapy group was lowest with cDAPT initiation at 17 days, although initiation of cDAPT throughout the 15-180 days window had similar point estimates. Bleeding risk was similar between the cDAPT and monotherapy groups for all time windows.