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Diabetes Care. 2018 Jun;41(6):1275-1284. doi: 10.2337/dc17-2224. Epub 2018 Apr 6.

Intensive Treat-to-Target Statin Therapy in High-Risk Japanese Patients With Hypercholesterolemia and Diabetic Retinopathy: Report of a Randomized Study.

Author information

1
Department of Endocrinology, Metabolism and Nephrology, Keio University School of Medicine, Tokyo, Japan hiito@keio.jp.
2
Department of Cardiovascular Medicine, The University of Tokyo Graduate School of Medicine, Tokyo, Japan.
3
Department of Clinical Medicine (Biostatistics and Pharmaceutical Medicine), School of Pharmacy, Kitasato University, Tokyo, Japan.
4
Department of Cardiovascular Medicine, Wakayama Medical University, Wakayama, Japan.
5
Department of Cardiovascular Medicine, Graduate School of Medicine Juntendo University, Tokyo, Japan.
6
Sakura Hospital, Fukuoka, Japan.
7
Department of Cardiology, Saitama Medical Center, Jichi Medical University, Saitama, Japan.
8
Department of Integrated Medicine and Informatics, Ehime University Graduate School of Medicine, Toon, Japan.
9
Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
10
Division of Endocrinology and Metabolism, Department of Internal Medicine, Jichi Medical University, Shimotsuke, Japan.
11
Division of Cardiology, Cardiovascular Center, Ageo Central General Hospital, Ageo, Japan.
12
Division of Nephrology, Endocrinology and Vascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
13
Kusatsu General Hospital, Kusatsu, Japan.
14
Department of Ophthalmology, The University of Tokyo Graduate School of Medicine, Tokyo, Japan.
15
Department of Neurology, Tokyo Women's Medical University School of Medicine, Tokyo, Japan.
16
Division of Cardiology, National Cerebral and Cardiovascular Center, Suita, Japan.
17
Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
18
Department of Medicine and Biological Science, Gunma University Graduate School of Medicine, Maebashi, Japan.
19
Department of Cardiology, Graduate School of Medicine Juntendo University, Tokyo, Japan.
20
Department of Ophthalmology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
21
Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
22
Department of Cardiovascular Medicine, Saga University, Saga, Japan.
23
Division of Nephrology, Endocrinology and Vascular Medicine, Tohoku University Hospital, Sendai, Japan.
24
First Department of Internal Medicine, Nara Medical University, Kashihara, Japan.
25
Department of Cardiology, Nippon Medical School Chiba Hokuso Hospital, Inzai, Japan.
26
Ideta Eye Clinic, Kumamoto, Japan.
27
Department of Cardiovascular Surgery, Tokyo Medical University Hachioji Medical Center, Hachioji, Japan.
28
Sugawara Medical Clinic, Tokyo, Japan.
29
Department of Cardiology, Jinnouchi Hospital, Kumamoto, Japan.
30
Department of Endocrinology and Metabolism, Yokohama City University School of Medicine, Yokohama, Japan.
31
Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan.
32
Department of EBM Research, Institute for Advancement of Clinical and Translational Science, Kyoto University Hospital, Kyoto, Japan.
33
Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan.
34
Department of Cardiovascular and Internal Medicine, Kanazawa University Graduate School of Medicine, Kanazawa, Japan.
35
Clinical Research Support Center, The University of Tokyo Hospital, Tokyo, Japan.
36
Yo Clinic, Kyoto, Japan.
37
Department of Clinical Cell Biology and Medicine, Chiba University Graduate School of Medicine, Chiba, Japan.
38
Sakakibara Heart Institute of Okayama, Okayama, Japan.
39
Division of Cardiology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan.
40
Kitano Hospital, The Tazuke Kofukai Medical Research Institute, Osaka, Japan.
41
Medical Innovation Center, Kyoto University Graduate School of Medicine, Kyoto, Japan.
42
Jichi Medical University, Shimotsuke, Japan.

Abstract

OBJECTIVE:

Diabetes is associated with high risk of cardiovascular (CV) events, particularly in patients with dyslipidemia and diabetic complications. We investigated the incidence of CV events with intensive or standard lipid-lowering therapy in patients with hypercholesterolemia, diabetic retinopathy, and no history of coronary artery disease (treat-to-target approach).

RESEARCH DESIGN AND METHODS:

In this multicenter, prospective, randomized, open-label, blinded end point study, eligible patients were randomly assigned (1:1) to intensive statin therapy targeting LDL cholesterol (LDL-C) <70 mg/dL (n = 2,518) or standard statin therapy targeting LDL-C 100-120 mg/dL (n = 2,524).

RESULTS:

Mean follow-up was 37 ± 13 months. LDL-C at 36 months was 76.5 ± 21.6 mg/dL in the intensive group and 104.1 ± 22.1 mg/dL in the standard group (P < 0.001). The primary end point events occurred in 129 intensive group patients and 153 standard group patients (hazard ratio [HR] 0.84 [95% CI 0.67-1.07]; P = 0.15). The relationship between the LDL-C difference in the two groups and the event reduction rate was consistent with primary prevention studies in patients with diabetes. Exploratory findings showed significantly fewer cerebral events in the intensive group (HR 0.52 [95% CI 0.31-0.88]; P = 0.01). Safety did not differ significantly between the two groups.

CONCLUSIONS:

We found no significant decrease in CV events or CV-associated deaths with intensive therapy, possibly because our between-group difference of LDL-C was lower than expected (27.7 mg/dL at 36 months of treatment). The potential benefit of achieving LDL-C <70 mg/dL in a treat-to-target strategy in high-risk patients deserves further investigation.

PMID:
29626074
DOI:
10.2337/dc17-2224
[Indexed for MEDLINE]

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