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

Abstract

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 versus 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/d plus ezetimibe 10 mg/d (combination group, N=3767) and those who received atorvastatin 40 mg/day or rosuvastatin 20 mg/day (HIS group, N=37670) 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] 0.440.95). 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 maybe a favorable choice for Asians who need strict lipid control but with concern of HS.