Delayed treatment with cilostazol key to preventing stroke recurrence

Commencing long-term dual antiplatelet therapy with cilostazol no less than 15 days after stroke proved to be a stronger method of secondary stroke prevention than standard monotherapy, according to study results published in Neurology.

“Early initiation of dual antiplatelet therapy (DAPT), within 30 days of stroke, using ticagrelor and aspirin, compared to aspirin alone, was proven to decrease the risk of the composite of stroke or death, but this combination increased severe bleeding,” Kazunori Toyoda, MD, PhD, of the department of cerebrovascular medicine at the National Cerebral and Cardiovascular Center in Japan, and colleagues wrote. “In addition, the effect at the second month or later has not been explored.”

Seeking to determine whether recurrent ischemic stroke risk was affected by the timing of dual medication vs. monotherapy administration after stroke onset, researchers conducted a subanalysis of a randomized controlled trial, in which 1,879 patients between 8 and 180 days after stroke onset received either aspirin or clopidogrel alone or a combination of cilostazol with aspirin or clopidogrel. The participants were divided into three groups, based on the initiation of trial treatment after stroke onset: 498 started either dual therapy or monotherapy between 8 and 14 days (8-14D), 467 between 15 and 28 days (15-28D) and 914 between 29 and 180 days (29-180D). The primary outcome for treatment was initial recurrence of ischemic stroke, with severe or life-threatening bleeding a secondary outcome.

The investigation revealed that dual therapy significantly reduced recurrence of ischemic stroke compared with monotherapy in both the 15-28D group (annualized rate 1.5% vs. 4.9%, respectively; aHR = 0.34; 95% CI, 0.12-0.95) and the 29-180D group (1.9% vs. 4.4%; aHR = 0.27; 95% CI, 0.12-0.63), but recurrence was roughly equal among the 8-14D group (4.5% for both; aHR = 1.02; 95% CI, 0.51-2.04).

Further, researchers found that incidence of severe or life-threatening bleeding was comparable between dual therapy and monotherapy participants across all three randomized groups.

“Long-term DAPT using cilostazol was more effective for secondary prevention of non-cardioembolic stroke than monotherapy in high-risk patients who started the medication 15 days or later after stroke onset without increasing hemorrhage risk,” Toyoda and colleagues wrote. “The finding suggests the feasibility of a seamless DAPT strategy after stroke, switching from (aspirin + clopidogrel) in the acute to subacute stage to (cilostazol + aspirin) or (cilostazol + clopidogrel) at 15 days or later. Clinical studies to prove this strategy would be needed.”