Tohoku J. Exp. Med., 2024 June, 263(2)

Risk of Hemorrhagic Stroke among Patients Treated with High-Intensity Statins versus Pitavastatin-Ezetimibe: A Population Based Study

Po-Sheng Chen,¹ Jia-Ling Lin,¹ Hui-Wen Lin,^1,2 Sheng-Hsiang Lin^2,3,4 and Yi-Heng Li¹

¹Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
²Biostatistics Consulting Center, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
³Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan
⁴Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan.

High-intensity statin (HIS) is recommended for high-risk patients in current guidelines. However, the risk of hemorrhagic stroke (HS) with HIS is a concern for Asians. Pitavastatin carries pharmacological differences compared with other statins. We compared the risk of HS in patients treated with pitavastatin-ezetimibe vs. HIS. We conducted a population-based, propensity score-matched cohort study using data from the Taiwan National Health Insurance Research Database. From January 2013 to December 2018, adults ( 18 years) who received pitavastatin 2-4 mg/day plus ezetimibe 10 mg/day (combination group, N = 3,767) and those who received atorvastatin 40 mg/day or rosuvastatin 20 mg/day (HIS group, N = 37,670) were enrolled. The primary endpoint was HS. We also assessed the difference of a composite safety endpoint of hepatitis or myopathy requiring hospitalization and new-onset diabetes mellitus. Multivariable Cox proportional hazards model was used to evaluate the relationship between study endpoints and different treatment. After a mean follow-up of 3.05 ± 1.66 years, less HS occurred in combination group (0.74%) than in HIS group (1.35%) [adjusted hazard ratio (aHR) 0.65, 95% confidence interval (CI) 0.44-0.95]. In subgroup analysis, the lower risk of HS in combination group was consistent among all pre-specified subgroups. There was no significant difference of the composite safety endpoint between the 2 groups (aHR 0.91, 95% CI 0.81-1.02). In conclusion, pitavastatin-ezetimibe combination treatment had less HS compared with high-intensity atorvastatin and rosuvastatin. Pitavastatin-ezetimibe may be a favorable choice for Asians who need strict lipid control but with concern of HS.

Key words —— diabetes mellitus; hemorrhagic stroke; lipids; myopathy; statins

© 2024 Tohoku University Medical Press

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Tohoku J. Exp. Med., 2024 June, 263(2), 105-113.

*These two authors contributed equally to this work.

Correspondence: Dr. Yi-Heng Li, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, 138 Sheng Li Road, Tainan 704, Taiwan.

e-mail: heng@mail.ncku.edu.tw

Sheng-Hsiang Lin, Biostatistics Consulting Center, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, and Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, 138 Sheng Li Road, Tainan 704, Taiwan.

e-mail: shlin922@mail.ncku.edu.tw