J Stroke.  2020 Jan;22(1):108-118. 10.5853/jos.2019.02551.

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

Affiliations
  • 1Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
  • 2Department of Neurology, Myongji Hospital, Hanyang University College of Medicine, Goyang, Korea
  • 3Department of Neurology, Eunpyeong St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
  • 4Department of Neurology, Inje University Ilsan Paik Hospital, Inje University College of Medicine, Goyang, Korea
  • 5Department of Neurology, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Korea
  • 6Department of Neurology, Kyungpook National University Hospital, School of Medicine, Kyungpook National University, Daegu, Korea
  • 7Clinical Research Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
  • 8Department of Biostatistics, Korea University, Seoul, Korea
  • 9Department of Neurology, Inha University Hospital, Incheon, Korea
  • 10Department of Neurology, Kyung Hee University Medical Center, Seoul, Korea
  • 11Department of Neurology, Chosun University Hospital, Chosun University College of Medicine, Gwangju, Korea
  • 12Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
  • 13Department of Neurology, Eulji General Hospital, Eulji University School of Medicine, Seoul, Korea
  • 14Department of Neurology, Hallym University Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea
  • 15Department of Neurology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea
  • 16Department of Neurology, Keimyung University Dongsan Medical Center, Keimyung University School of Medicine, Daegu, Korea
  • 17Department of Neurology, Korea University Ansan Hospital, Korea University College of Medicine, Ansan, Korea
  • 18Department of Neurology, Konkuk University School of Medicine, Seoul, Korea
  • 19Department of Neurology, Inje University Busan Paik Hospital, Inje University College of Medicine, Busan, Korea
  • 20Department of Neurology, Kangwon National University Hospital, Kangwon National University School of Medicine, Chuncheon, Korea
  • 21Department of Neurology, Dong-A University Hospital, Dong-A University College of Medicine, Busan, Korea
  • 22Department of Neurology, Chonnam National University Medical School, Gwangju, Korea
  • 23Department of Neurology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea

Abstract

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.

Keyword

Cholesterol, HDL; Secondary prevention; Cilostazol; Probucol; Cholesterol ester transfer proteins
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