Ezetimibe-Simvastatin Therapy Reduce Recurrent Ischemic Stroke Risks in Type 2 Diabetic Patients.
Statin is the main lipid-lowering therapy for type 2 diabetes mellitus patients. Recent evidence suggested the cardiovascular protective effects of ezetimibe-simvastatin in acute coronary syndrome patients.



To investigate the effect of ezetimibe-simvastatin combination therapy on stroke prevention among diabetic stroke patients. Design, Setting, Participants, and Outcome Measures: This is a retrospective cohort study. Between March 1, 2009 and December 31, 2011, all patients with type 2 diabetes mellitus in Taiwan's National Health Insurance Research Database were screened. Those admitted for ischemic stroke (IS) were recruited and divided into 10-mg ezetimibe-20-mg simvastatin (EZ-SIM), 40-mg atorvastatin (ATOR), and 20-mg simvastatin (SIM) groups for further analyses. The primary outcomes were IS, myocardial infarction, and death from any cause. Patients were followed from index hospitalization to the date of death, loss of follow-up, or study termination.



During the 34-month follow-up period, the risk of recurrent IS in the SIM group was higher than that of the ATOR (hazard ratio [HR], 2.03; 95% confidence interval [CI], 1.46-2.82) and EZ-SIM (HR, 1.69; 95% CI, 1.14-2.50) groups. The risk of recurrent IS was not significantly lower in the EZ-SIM compared with the ATOR group (HR, 1.20; 95% CI, 0.85-1.69). The incidence of composite endpoint was highest in the SIM group (28.2%), followed by the ATOR (16.1%) and EZ-SIM (15.4%) groups. The multivariate adjusted survival curve showed lower trends of recurrent IS in the EZ-SIM and ATOR groups compared with the SIM group.



High-potency lipid-lowering therapy effectively reduces the risk of recurrent IS in diabetic patients regardless of ATOR or EZ-SIM combination therapy.
Stroke Center and Department of Neurology (C.-H.L., T.-H.L.), Chang Gung Memorial Hospital, Linkou Medical Center, Chang Gung University College of Medicine, Taoyuan, Taiwan 61363; Division of Cardiology (T.-H.C., M.-J.H., W.-J.C.), Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Keelung, Taiwan 61363; Division of Cardiology (M.-S.L.), Department of Internal Medicine, Chang Gung Memorial Hospital, Yunlin, Taiwan 61363; and Department of Medicine (C.-M.C., Y.-S.L.), College of Medicine, Chang Gung University, Taoyuan, and Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan 61363.
Chi-Hung
CH
Liu
Stroke Center and Department of Neurology (C.-H.L., T.-H.L.), Chang Gung Memorial Hospital, Linkou Medical Center, Chang Gung University College of Medicine, Taoyuan, Taiwan 61363; Division of Cardiology (T.-H.C., M.-J.H., W.-J.C.), Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Keelung, Taiwan 61363; Division of Cardiology (M.-S.L.), Department of Internal Medicine, Chang Gung Memorial Hospital, Yunlin, Taiwan 61363; and Department of Medicine (C.-M.C., Y.-S.L.), College of Medicine, Chang Gung University, Taoyuan, and Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan 61363.
Tien-Hsing
TH
Chen
Stroke Center and Department of Neurology (C.-H.L., T.-H.L.), Chang Gung Memorial Hospital, Linkou Medical Center, Chang Gung University College of Medicine, Taoyuan, Taiwan 61363; Division of Cardiology (T.-H.C., M.-J.H., W.-J.C.), Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Keelung, Taiwan 61363; Division of Cardiology (M.-S.L.), Department of Internal Medicine, Chang Gung Memorial Hospital, Yunlin, Taiwan 61363; and Department of Medicine (C.-M.C., Y.-S.L.), College of Medicine, Chang Gung University, Taoyuan, and Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan 61363.
Ming-Shyan
MS
Lin
Stroke Center and Department of Neurology (C.-H.L., T.-H.L.), Chang Gung Memorial Hospital, Linkou Medical Center, Chang Gung University College of Medicine, Taoyuan, Taiwan 61363; Division of Cardiology (T.-H.C., M.-J.H., W.-J.C.), Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Keelung, Taiwan 61363; Division of Cardiology (M.-S.L.), Department of Internal Medicine, Chang Gung Memorial Hospital, Yunlin, Taiwan 61363; and Department of Medicine (C.-M.C., Y.-S.L.), College of Medicine, Chang Gung University, Taoyuan, and Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan 61363.
Ming-Jui
MJ
Hung
Stroke Center and Department of Neurology (C.-H.L., T.-H.L.), Chang Gung Memorial Hospital, Linkou Medical Center, Chang Gung University College of Medicine, Taoyuan, Taiwan 61363; Division of Cardiology (T.-H.C., M.-J.H., W.-J.C.), Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Keelung, Taiwan 61363; Division of Cardiology (M.-S.L.), Department of Internal Medicine, Chang Gung Memorial Hospital, Yunlin, Taiwan 61363; and Department of Medicine (C.-M.C., Y.-S.L.), College of Medicine, Chang Gung University, Taoyuan, and Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan 61363.
Chang-Ming
CM
Chung
Stroke Center and Department of Neurology (C.-H.L., T.-H.L.), Chang Gung Memorial Hospital, Linkou Medical Center, Chang Gung University College of Medicine, Taoyuan, Taiwan 61363; Division of Cardiology (T.-H.C., M.-J.H., W.-J.C.), Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Keelung, Taiwan 61363; Division of Cardiology (M.-S.L.), Department of Internal Medicine, Chang Gung Memorial Hospital, Yunlin, Taiwan 61363; and Department of Medicine (C.-M.C., Y.-S.L.), College of Medicine, Chang Gung University, Taoyuan, and Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan 61363.
Wen-Jin
WJ
Cherng
Stroke Center and Department of Neurology (C.-H.L., T.-H.L.), Chang Gung Memorial Hospital, Linkou Medical Center, Chang Gung University College of Medicine, Taoyuan, Taiwan 61363; Division of Cardiology (T.-H.C., M.-J.H., W.-J.C.), Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Keelung, Taiwan 61363; Division of Cardiology (M.-S.L.), Department of Internal Medicine, Chang Gung Memorial Hospital, Yunlin, Taiwan 61363; and Department of Medicine (C.-M.C., Y.-S.L.), College of Medicine, Chang Gung University, Taoyuan, and Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan 61363.
Tsong-Hai
TH
Lee
Stroke Center and Department of Neurology (C.-H.L., T.-H.L.), Chang Gung Memorial Hospital, Linkou Medical Center, Chang Gung University College of Medicine, Taoyuan, Taiwan 61363; Division of Cardiology (T.-H.C., M.-J.H., W.-J.C.), Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Keelung, Taiwan 61363; Division of Cardiology (M.-S.L.), Department of Internal Medicine, Chang Gung Memorial Hospital, Yunlin, Taiwan 61363; and Department of Medicine (C.-M.C., Y.-S.L.), College of Medicine, Chang Gung University, Taoyuan, and Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan 61363.
Yu-Sheng
YS
Lin
D000368:Aged; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D000069499:Ezetimibe, Simvastatin Drug Combination / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D002546:Ischemic Attack, Transient / Q000401:mortality / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D012189:Retrospective Studies; D012307:Risk Factors; D020521:Stroke / Q000401:mortality / Q000517:prevention & control*; D013624:Taiwan / Q000453:epidemiology
D000924:Anticholesteremic Agents; D000069499:Ezetimibe, Simvastatin Drug Combination