Cilostazol versus aspirin in ischemic stroke with cerebral microbleeds versus prior intracerebral hemorrhage

Background: In PreventIon of CArdiovascular Events in Ischaemic Stroke Patients with High Risk of Cerebral HaemOrrhage (PICASSO), cilostazol versus aspirin was comparable for the end points of cerebral hemorrhage and major vascular events. However, underlying hemorrhage-prone lesions could modify the treatment effect. Aims: We explored whether the safety and efficacy of cilostazol versus aspirin would differ between hemorrhage-prone lesions (multiple cerebral microbleeds vs. prior intracerebral hemorrhage). Methods: In this post hoc analysis of PICASSO, we divided patients into the cerebral microbleeds and prior intracerebral hemorrhage subgroups. The primary safety end point was the first occurrence of cerebral hemorrhage. The primary efficacy end point was the composite of stroke, myocardial infarction, or vascular death. Results: Of 1512 patients, 903 (59.7%) had multiple cerebral microbleeds and 609 (40.3%) had prior intracerebral hemorrhage. The cerebral hemorrhage risk was lower with cilostazol versus aspirin (0.12%/year vs. 1.49%/year; hazard ratio, 0.08 [95% confidence interval 0.01–0.60]; p = 0.015) in the cerebral microbleeds subgroup, but was not different (1.26%/year vs. 0.79%/year; hazards ratio 1.60 [0.52–4.90]; p = 0.408) in the prior intracerebral hemorrhage subgroup. The interaction of treatment-by-subgroup was significant (p_interaction = 0.011). For the composite of major vascular events, there was a trend toward a lower risk with cilostazol versus aspirin (3.56%/year vs. 5.53%/year; hazards ratio 0.64 [0.41–1.01]; p = 0.056) in the cerebral microbleeds subgroup, but was comparable (5.21%/year vs. 5.05%/year; hazards ratio 1.03 [0.63–1.67]; p = 0.913) in the prior intracerebral hemorrhage subgroup without a significant treatment-by-subgroup interaction (p_interaction = 0.165). Conclusions: Cilostazol versus aspirin might be a better option in ischemic stroke with multiple cerebral microbleeds, but confirmatory trials are needed. Clinical Trial Registration: URL:http://www.clinicaltrials.gov. NCT01013532.