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Changes in High-Density Lipoprotein Cholesterol and Risks of Cardiovascular Events: A Post Hoc Analysis from the PICASSO Trial

 Eun-Jae Lee  ;  Sun U Kwon  ;  Jong-Ho Park  ;  Yong-Jae Kim  ;  Keun-Sik Hong  ;  Sungwook Yu  ;  Yang-Ha Hwang  ;  Ji Sung Lee  ;  Juneyoung Lee  ;  Joung-Ho Rha  ;  Sung Hyuk Heo  ;  Sung Hwan Ahn  ;  Woo-Keun Seo  ;  Jong-Moo Park  ;  Ju-Hun Lee  ;  Jee-Hyun Kwon  ;  Sung-Il Sohn  ;  Jin-Man Jung  ;  Hahn Young Kim  ;  Eung-Gyu Kim  ;  Sung Hun Kim  ;  Jae-Kwan Cha  ;  Man-Seok Park  ;  Hyo Suk Nam  ;  Dong-Wha Kang 
 JOURNAL OF STROKE, Vol.22(1) : 108-118, 2020-01 
Journal Title
Issue Date
Cholesterol ester transfer proteins ; Cholesterol, HDL ; Cilostazol ; Probucol ; Secondary prevention
Background and purpose: Whether pharmacologically altered high-density lipoprotein cholesterol (HDL-C) affects the risk of cardiovascular events is unknown. Recently, we have reported the Prevention of Cardiovascular Events in Asian Patients with Ischaemic Stroke at High Risk of Cerebral Haemorrhage (PICASSO) trial that demonstrated the non-inferiority of cilostazol to aspirin and superiority of probucol to non-probucol for cardiovascular prevention in ischemic stroke patients (clinicaltrials.gov: NCT01013532). We aimed to determine whether on-treatment HDL-C changes by cilostazol and probucol influence the treatment effect of each study medication during the PICASSO study. Methods: Of the 1,534 randomized patients, 1,373 (89.5%) with baseline cholesterol parameters were analyzed. Efficacy endpoint was the composite of stroke, myocardial infarction, and cardiovascular death. Cox proportional hazards regression analysis examined an interaction between the treatment effect and changes in HDL-C levels from randomization to 1 month for each study arm. Results: One-month post-randomization mean HDL-C level was significantly higher in the cilostazol group than in the aspirin group (1.08 mmol/L vs. 1.00 mmol/L, P<0.001). The mean HDL-C level was significantly lower in the probucol group than in the non-probucol group (0.86 mmol/L vs. 1.22 mmol/L, P<0.001). These trends persisted throughout the study. In both study arms, no significant interaction was observed between HDL-C changes and the assigned treatment regarding the risk of the efficacy endpoint. Conclusions: Despite significant HDL-C changes, the effects of cilostazol and probucol treatment on the risk of cardiovascular events were insignificant. Pharmacologically altered HDL-C levels may not be reliable prognostic markers for cardiovascular risk.
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1. College of Medicine (의과대학) > Dept. of Neurology (신경과학교실) > 1. Journal Papers
Yonsei Authors
Nam, Hyo Suk(남효석) ORCID logo https://orcid.org/0000-0002-4415-3995
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