Long-Term Use of Statins Lowering the Risk of Rehospitalization Caused by Ischemic Stroke Among Middle-Aged Hyperlipidemic Patients: A Population-Based Study

Jiu-Haw Yin; Giia-Sheun Peng; Kang-Hua Chen; Chi-Ming Chu; Wu-Chien Chien; Li-Ting Kao; Chia-Chao Wu; Chih-Wei Yang; Wen-Chiuan Tsai; Wei-Zhi Lin; Yi-Syuan Wu; Hung-Che Lin; Yu-Tien Chang

doi:10.3389/fphar.2021.741094

Long-Term Use of Statins Lowering the Risk of Rehospitalization Caused by Ischemic Stroke Among Middle-Aged Hyperlipidemic Patients: A Population-Based Study

Front Pharmacol. 2021 Oct 18:12:741094. doi: 10.3389/fphar.2021.741094. eCollection 2021.

Authors

Jiu-Haw Yin^{1

2}, Giia-Sheun Peng^{1

2}, Kang-Hua Chen^{3

4}, Chi-Ming Chu^{5

6

7

8

9}, Wu-Chien Chien¹⁰, Li-Ting Kao^{5

11

12

13}, Chia-Chao Wu¹⁴, Chih-Wei Yang¹⁵, Wen-Chiuan Tsai¹⁶, Wei-Zhi Lin^{13

17}, Yi-Syuan Wu¹³, Hung-Che Lin^{18

19

20}, Yu-Tien Chang⁵

Affiliations

¹ Department of Neurology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
² Division of Neurology, Department of Internal Medicine, Taipei Veterans General Hospital, Hsinchu Branch, Hsinchu County, Taipei, Taiwan.
³ Associate Professor, School of Nursing, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
⁴ Associate Research Fellow, Department of Nursing, Chang Gung Memorial Hospital, Tao-Yuan Branch, Taoyuan, Taiwan.
⁵ School of Public Health, National Defense Medical Center, Taipei, Taiwan.
⁶ Department of Surgery, Songshan Branch of Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
⁷ Division of Biostatistics and Informatics, Department of Epidemiology, School of Public Health, National Defense Medical Center, Taipei, Taiwan.
⁸ Department of Public Health, China Medical University, Taichung, Taiwan.
⁹ Department of Healthcare Administration and Medical Informatics College of Health Sciences, Kaohsiung Medical University, Kaohsiung, Taiwan.
¹⁰ Department of Medical Research, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
¹¹ Department of Pharmacy Practice, Tri-Service General Hospital, Taipei, Taiwan.
¹² School of Pharmacy, National Defense Medical Center, Taipei, Taiwan.
¹³ Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan.
¹⁴ Division of Nephrology, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
¹⁵ Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
¹⁶ Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
¹⁷ School of Medicine, National Defense Medical Center, Taipei, Taiwan.
¹⁸ Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan.
¹⁹ Department of Otolaryngology-Head and Neck Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
²⁰ Hualien Armed Forces General Hospital, Hualien, Taiwan.

Abstract

Background: The long-term effects of statin use on rehospitalization due to ischemic stroke (reHospIS) in hyperlipidemic patients are still unknown. Therefore, we aimed to assess the long-term risks of reHospIS for hyperlipidemic patients who were taking statins and nonstatin lipid-lowering medicines on a regular basis. Methods and Materials: The National Health Insurance Research Database in Taiwan was used to conduct a 6-year cohort study of patients >45 years old (n = 9,098) who were newly diagnosed with hyperlipidemia and hospitalized for the first or second time due to ischemic stroke (IS). The risk of reHospIS was assessed using Cox proportional hazards regression model. Results: Nonstatin lipid-lowering medicines regular users were associated with a higher risk of reHospIS compared to stains users (hazard ratio, HR = 1.29-1.39, p < 0.05). Rosuvastatin was the most preferred lipid-lowering medicine with lower HRs of reHospIS in hyperlipidemic patients whether they developed diabetes or not. Bezafibrate regular users of hyperlipidemic patients developing diabetes (HR = 2.15, p < 0.01) had nearly 50% lower reHospIS risks than those without diabetes (HR = 4.27, p < 0.05). Age, gender, drug dosage, comorbidities of diabetes and heart failure (HF), and characteristics of the first hospitalization due to IS were all adjusted in models. Moreover, increasing trends of HRs of reHospIS were observed from Rosuvastatin, nonstatin lipid-lowering medicines, Lovastatin, and Gemfibrozil to Bezafibrate users. Conclusion: Statins were associated with long-term secondary prevention of reHospIS for hyperlipidemic patients. Rosuvastatin seemed to have the best protective effects. On the other hand, Bezafibrate appears to be beneficial for hyperlipidemic patients developing diabetes. Further research into the combination treatment of statin and nonstatin lipid-lowering medicines in hyperlipidemic patients developing diabetes is warranted.

Keywords: diabetes mellitus; hyperlipidemia; ischemic stroke; lipid-lowering medicines; rehospitalization; secondary prevention; statins.