Achieving LDL cholesterol target levels <1.81 mmol/L may provide extra cardiovascular protection in patients at high risk: Exploratory analysis of the Standard Versus Intensive Statin Therapy for Patients with Hypercholesterolaemia and Diabetic Retinopathy study.

Abstract

AIMS:

To assess the benefits of intensive statin therapy on reducing cardiovascular (CV) events in patients with type 2 diabetes complicated with hyperlipidaemia and retinopathy in a primary prevention setting in Japan. In the intension-to-treat population, intensive therapy [targeting LDL cholesterol <1.81 mmol/L (<70 mg/dL)] was no more effective than standard therapy [LDL cholesterol ≥2.59 to <3.10 mmol/L (≥100 to <120 mg/dL)]; however, after 3 years, the intergroup difference in LDL cholesterol was only 0.72 mmol/L (27.7 mg/dL), and targeted levels were achieved in <50% of patients. We hypothesized that the intergroup difference in CV events would have been statistically significant if more patients had been successfully treated to target.

MATERIALS AND METHODS:

This exploratory post hoc analysis focused on intergroup data from patients who achieved their target LDL cholesterol levels. The primary endpoint was the composite incidence of CV events. A Cox proportional hazards model was used to estimate hazard ratios (HRs) for incidence of the primary endpoint in patients who achieved target LDL cholesterol levels in each group.

RESULTS:

Data were analysed from 1909 patients (intensive: 703; standard: 1206) who achieved target LDL cholesterol levels. LDL cholesterol at 36 months was 1.54 ± 0.30 mmol/L (59.7 ± 11.6 mg/dL) in the intensive group and 2.77 ± 0.46 mmol/L (107.1 ± 17.8 mg/dL) in the standard group (P < 0.05). After adjusting for baseline prognostic factors, the composite incidence of CV events or deaths associated with CV events was significantly lower in the intensive than the standard group (HR 0.48; 95% confidence interval 0.28-0.82; P = 0.007).

CONCLUSIONS:

This post hoc analysis suggests that achieving LDL cholesterol target levels <1.81 mmol/L may more effectively reduce CV events than achieving target levels ≥2.59 to <3.10 mmol/L in patients with hypercholesterolaemia and diabetic retinopathy.

• 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, obesity & metabolism (Diabetes Obes Metab) Vol. 21 Issue 4 Pg. 791-800 (04 2019) ISSN: 1463-1326 [Electronic] England
• PMID: 30393955 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Chemical References

• Cholesterol, LDL
• Glycated Hemoglobin A
• Hydroxymethylglutaryl-CoA Reductase Inhibitors
• hemoglobin A1c protein, human

Topics

• Aged
• Cardiovascular Diseases (epidemiology, mortality, prevention & control)
• Cholesterol, LDL (metabolism)
• Diabetes Mellitus, Type 2 (complications, metabolism)
• Diabetic Retinopathy (etiology, metabolism)
• Female
• Glycated Hemoglobin (metabolism)
• Humans
• Hydroxymethylglutaryl-CoA Reductase Inhibitors (therapeutic use)
• Hyperlipidemias (complications, drug therapy, metabolism)
• Intention to Treat Analysis
• Japan
• Male
• Middle Aged
• Patient Care Planning
• Primary Prevention
• Proportional Hazards Models