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 KimSung Hun Kim, Jae Kwan Cha, Man Seok Park, Hyo Suk Nam, Dong Wha Kang

    Research output: Contribution to journalArticlepeer-review

    1 Citation (Scopus)


    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 ( 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.

    Original languageEnglish
    Pages (from-to)108-118
    Number of pages11
    JournalJournal of Stroke
    Issue number1
    Publication statusPublished - 2020 Jan

    Bibliographical note

    Funding Information:
    Korea Otsuka Pharmaceutical for PICASSO study, Ministry of Health & Welfare (HI18C2383) and Ministry of Science and ICT (NRF-2018M3A9E8066249), Republic of Korea.

    Publisher Copyright:
    © 2020 Korean Stroke Society.


    • Cholesterol
    • Cholesterol ester transfer proteins
    • Cilostazol
    • HDL
    • Probucol
    • Secondary prevention

    ASJC Scopus subject areas

    • Clinical Neurology
    • Cardiology and Cardiovascular Medicine


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