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

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.

• Authors: Hiroshi Itoh, Issei Komuro, Masahiro Takeuchi, Takashi Akasaka, Hiroyuki Daida, Yoshiki Egashira, Hideo Fujita, Jitsuo Higaki, Ken-Ichi Hirata, Shun Ishibashi, Takaaki Isshiki, Sadayoshi Ito, Atsunori Kashiwagi, Satoshi Kato, Kazuo Kitagawa, Masafumi Kitakaze, Takanari Kitazono, Masahiko Kurabayashi, Katsumi Miyauchi, Tomoaki Murakami, Toyoaki Murohara, Koichi Node, Susumu Ogawa, Yoshihiko Saito, Yoshihiko Seino, Takashi Shigeeda, Shunya Shindo, Masahiro Sugawara, Seigo Sugiyama, Yasuo Terauchi, Hiroyuki Tsutsui, Kenji Ueshima, Kazunori Utsunomiya, Masakazu Yamagishi, Tsutomu Yamazaki, Shoei Yo, Koutaro Yokote, Kiyoshi Yoshida, Michihiro Yoshimura, Nagahisa Yoshimura, Kazuwa Nakao, Ryozo Nagai, EMPATHY Investigators
• Journal: Diabetes care (Diabetes Care) Vol. 41 Issue 6 Pg. 1275-1284 (06 2018) ISSN: 1935-5548 [Electronic] United States
• PMID: 29626074 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 by the American Diabetes Association.

Chemical References

• Cholesterol, LDL
• Hydroxymethylglutaryl-CoA Reductase Inhibitors

Topics

• Aged
• Cardiovascular Diseases (blood, epidemiology)
• Cholesterol, LDL (blood)
• Comorbidity
• Diabetic Retinopathy (blood, complications, epidemiology)
• Female
• Humans
• Hydroxymethylglutaryl-CoA Reductase Inhibitors (blood, therapeutic use)
• Hypercholesterolemia (blood, drug therapy, epidemiology)
• Incidence
• Japan (epidemiology)
• Male
• Middle Aged
• Prospective Studies