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Efficacy of intensive lipid-lowering therapy with statins stratified by blood pressure levels in patients with type 2 diabetes mellitus and retinopathy: Insight from the EMPATHY study

Hypertension Research volume 44, pages 1606–1616 (2021)Cite this article

Abstract

Intensive lipid-lowering therapy is recommended in individuals exhibiting type 2 diabetes mellitus (T2DM) with microvascular complications (as high-risk patients), even without known cardiovascular disease (CVD). However, evidence is insufficient to stratify the patients who would benefit from intensive therapy among them. Hypertension is a major risk factor, and uncontrolled blood pressure (BP) is associated with increased CVD risk. We evaluated the efficacy of intensive vs. standard statin therapy for primary CVD prevention among T2DM patients with retinopathy stratified by BP levels. We used the dataset from the EMPATHY study, which compared intensive statin therapy targeting low-density lipoprotein cholesterol (LDL-C) levels of <70 mg/dL and standard therapy targeting LDL-C levels ranging from ≥100 to <120 mg/dL in T2DM patients with retinopathy without known CVD. A total of 4980 patients were divided into BP ≥ 130/80 mmHg (systolic BP ≥ 130 mmHg and/or diastolic BP ≥ 80 mmHg, n = 3335) and BP < 130/80 mmHg (n = 1645) subgroups by baseline BP levels. During the median follow-up of 36.8 months, 281 CVD events were observed. Consistent with previous studies, CVD events occurred more frequently in the BP ≥ 130/80 mmHg subgroup than in the BP < 130/80 mmHg subgroup (P < 0.001). In the BP ≥ 130/80 mmHg subgroup, intensive statin therapy was associated with lower CVD risk (HR 0.70, P = 0.015) than standard therapy after adjustment. No such association was observed in the BP < 130/80 mmHg subgroup. The interaction between BP subgroup and statin therapy was significant. In conclusion, intensive statin therapy targeting LDL-C < 70 mg/dL provided benefits in primary CVD prevention when compared with standard therapy among T2DM patients with retinopathy and BP ≥ 130/80 mmHg.

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  1. These authors contributed equally: Keisuke Shinohara, Shota Ikeda

Authors and Affiliations

  1. Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan

    Keisuke Shinohara, Shota Ikeda, Nobuyuki Enzan, Shouji Matsushima, Takeshi Tohyama, Kouta Funakoshi & Hiroyuki Tsutsui

  2. Center for Clinical and Translational Research, Kyushu University Hospital, Fukuoka, Japan

    Keisuke Shinohara, Takeshi Tohyama, Kouta Funakoshi & Junji Kishimoto

  3. Department of Endocrinology, Metabolism and Nephrology, Keio University School of Medicine, Tokyo, Japan

    Hiroshi Itoh

  4. Department of Cardiovascular Medicine, The University of Tokyo Graduate School of Medicine, Tokyo, Japan

    Issei Komuro

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KS reports grants from Daiichi Sankyo and Nippon Boehringer Ingelheim. HI reports grants and/or personal fees from Shionogi, Takeda Pharmaceutical, Nippon Boehringer Ingelheim, Daiichi Sankyo, MSD, Mitsubishi Tanabe Pharma, Sumitomo Dainippon Pharma, Astellas Pharma, Kyowa Kirin, Ono Pharmaceutical, Chugai Pharmaceutical, Novartis Pharma, Kao, Mochida Pharmaceutical, Oriental Yeast, Abbott Japan, Bayer Yakuhin, LifeScan Japan, SBI Pharmaceuticals, Nipro, and Wakunaga Pharmaceutical. IK reports grants and/or personal fees from Takeda Pharmaceutical, Nippon Boehringer Ingelheim, Astellas Pharma, Daiichi Sankyo, Otsuka Pharmaceutical, MSD, Mitsubishi Tanabe Pharma, Bristol-Myers Squibb, Ono Pharmaceutical, AstraZeneca, Novartis Pharma, Bayer Yakuhin, Pfizer Japan, Idorsia Pharmaceuticals Japan, and Teijin Pharma. HT reports grants and/or personal fees from Daiichi Sankyo, Novartis Pharma, Otsuka Pharmaceutical, Pfizer Japan, Mitsubishi Tanabe Pharma, Teijin Pharma, Nippon Boehringer Ingelheim, Bayer Yakuhin, Bristol-Myers Squibb, AstraZeneca, Ono Pharmaceutical, Kowa, Japan Tobacco, IQVIA Service Japan, Omron Healthcare, MEDINET, Medical Innovation Kyushu, Abbott Medical Japan, Teijin Home Healthcare, and Boston Scientific Japan. The other authors report no competing interests.

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Shinohara, K., Ikeda, S., Enzan, N. et al. Efficacy of intensive lipid-lowering therapy with statins stratified by blood pressure levels in patients with type 2 diabetes mellitus and retinopathy: Insight from the EMPATHY study. Hypertens Res 44, 1606–1616 (2021). https://doi.org/10.1038/s41440-021-00734-x

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