Hong-Kyun Park1, Ji Sung Lee2, Bum Joon Kim3, Jong-Ho Park4, Yong-Jae Kim5, Sungwook Yu6, Yang-Ha Hwang7, Joung-Ho Rha8, Sung Hyuk Heo3, Seong Hwan Ahn9, Woo-Keun Seo10, Jong-Moo Park11, Ju-Hun Lee12, Jee-Hyun Kwon13, Sung-Il Sohn14, Jin-Man Jung15, Sun U Kwon16, Keun-Sik Hong1. 1. Department of Neurology, Inje University Ilsan Paik Hospital, Goyang, Korea. 2. Clinical Research Center, Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. 3. Department of Neurology, Kyung Hee University Medical Center, Seoul, Korea. 4. Department of Neurology, Myungji Hospital, Hanyang University College of Medicine, Goyang, Korea. 5. Department of Neurology, Eunpyeong St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea. 6. Department of Neurology, Anam Hospital, Korea University, Seoul, Korea. 7. Department of Neurology, Kyungpook National University Hospital, Daegu, Korea. 8. Department of Neurology, Inha University Hospital, Incheon, Korea. 9. Department of Neurology, Chosun University School of Medicine and Hospital, Gwangju, Korea. 10. Department of Neurology, Samsung Medical Center, Sunkyunkwan University, Seoul, Korea. 11. Department of Neurology, Nowon Eulji Medical Center, Eulji University, Seoul, Korea. 12. Department of Neurology, Kangdong Sacred Heart Hospital, Hallym University, Seoul, Korea. 13. Department of Neurology, Ulsan University Hospital, Ulsan University, Ulsan, Korea. 14. Department of Neurology, Dongsan Medical Center, Keimyung University, Daegu, Korea. 15. Department of Neurology, Ansan Hospital, Korea University, Seoul, Korea. 16. Department of Neurology, Asan Medical Center, Ulsan University, Seoul, Korea.
Abstract
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 (pinteraction = 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 (pinteraction = 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.
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 (pinteraction = 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 (pinteraction = 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.
Authors: Brian Mac Grory; Shadi Yaghi; Charlotte Cordonnier; Luciano A Sposato; Jose G Romano; Seemant Chaturvedi Journal: Circ Res Date: 2022-04-14 Impact factor: 23.213