Intensive treat-to-target statin therapy in high-risk Japanese patients with hypercholesterolemia and diabetic retinopathy

Report of a randomized study

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 & 22 others 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

Research output: Contribution to journalArticle

4 Citations (Scopus)

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± 13months. LDL-C at 36 months was 76.5± 21.6mg/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.

Original languageEnglish
Pages (from-to)1275-1284
Number of pages10
JournalDiabetes care
Volume41
Issue number6
DOIs
Publication statusPublished - Jun 1 2018

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Hydroxymethylglutaryl-CoA Reductase Inhibitors
Diabetic Retinopathy
Hypercholesterolemia
LDL Cholesterol
Therapeutics
Diabetes Complications
Primary Prevention
Dyslipidemias
Coronary Artery Disease
Research Design
Lipids
Safety
Incidence

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Advanced and Specialised Nursing

Cite this

Intensive treat-to-target statin therapy in high-risk Japanese patients with hypercholesterolemia and diabetic retinopathy : Report of a randomized study. / Itoh, Hiroshi; Komuro, Issei; Takeuchi, Masahiro; Akasaka, Takashi; Daida, Hiroyuki; Egashira, Yoshiki; Fujita, Hideo; Higaki, Jitsuo; Hirata, Ken Ichi; Ishibashi, Shun; Isshiki, Takaaki; Ito, Sadayoshi; Kashiwagi, Atsunori; Kato, Satoshi; Kitagawa, Kazuo; Kitakaze, Masafumi; Kitazono, Takanari; Kurabayashi, Masahiko; Miyauchi, Katsumi; Murakami, Tomoaki; Murohara, Toyoaki; Node, Koichi; Ogawa, Susumu; Saito, Yoshihiko; Seino, Yoshihiko; Shigeeda, Takashi; Shindo, Shunya; Sugawara, Masahiro; Sugiyama, Seigo; Terauchi, Yasuo; Tsutsui, Hiroyuki; Ueshima, Kenji; Utsunomiya, Kazunori; Yamagishi, Masakazu; Yamazaki, Tsutomu; Yo, Shoei; Yokote, Koutaro; Yoshida, Kiyoshi; Yoshimura, Michihiro; Yoshimura, Nagahisa; Nakao, Kazuwa; Nagai, Ryozo.

In: Diabetes care, Vol. 41, No. 6, 01.06.2018, p. 1275-1284.

Research output: Contribution to journalArticle

Itoh, H, Komuro, I, Takeuchi, M, Akasaka, T, Daida, H, Egashira, Y, Fujita, H, Higaki, J, Hirata, KI, Ishibashi, S, Isshiki, T, Ito, S, Kashiwagi, A, Kato, S, Kitagawa, K, Kitakaze, M, Kitazono, T, Kurabayashi, M, Miyauchi, K, Murakami, T, Murohara, T, Node, K, Ogawa, S, Saito, Y, Seino, Y, Shigeeda, T, Shindo, S, Sugawara, M, Sugiyama, S, Terauchi, Y, Tsutsui, H, Ueshima, K, Utsunomiya, K, Yamagishi, M, Yamazaki, T, Yo, S, Yokote, K, Yoshida, K, Yoshimura, M, Yoshimura, N, Nakao, K & Nagai, R 2018, 'Intensive treat-to-target statin therapy in high-risk Japanese patients with hypercholesterolemia and diabetic retinopathy: Report of a randomized study', Diabetes care, vol. 41, no. 6, pp. 1275-1284. https://doi.org/10.2337/dc17-2224
Itoh, Hiroshi ; Komuro, Issei ; Takeuchi, Masahiro ; Akasaka, Takashi ; Daida, Hiroyuki ; Egashira, Yoshiki ; Fujita, Hideo ; Higaki, Jitsuo ; Hirata, Ken Ichi ; Ishibashi, Shun ; Isshiki, Takaaki ; Ito, Sadayoshi ; Kashiwagi, Atsunori ; Kato, Satoshi ; Kitagawa, Kazuo ; Kitakaze, Masafumi ; Kitazono, Takanari ; Kurabayashi, Masahiko ; Miyauchi, Katsumi ; Murakami, Tomoaki ; Murohara, Toyoaki ; Node, Koichi ; Ogawa, Susumu ; Saito, Yoshihiko ; Seino, Yoshihiko ; Shigeeda, Takashi ; Shindo, Shunya ; Sugawara, Masahiro ; Sugiyama, Seigo ; Terauchi, Yasuo ; Tsutsui, Hiroyuki ; Ueshima, Kenji ; Utsunomiya, Kazunori ; Yamagishi, Masakazu ; Yamazaki, Tsutomu ; Yo, Shoei ; Yokote, Koutaro ; Yoshida, Kiyoshi ; Yoshimura, Michihiro ; Yoshimura, Nagahisa ; Nakao, Kazuwa ; Nagai, Ryozo. / Intensive treat-to-target statin therapy in high-risk Japanese patients with hypercholesterolemia and diabetic retinopathy : Report of a randomized study. In: Diabetes care. 2018 ; Vol. 41, No. 6. pp. 1275-1284.
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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± 13months. LDL-C at 36 months was 76.5± 21.6mg/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.",
author = "Hiroshi Itoh and Issei Komuro and Masahiro Takeuchi and Takashi Akasaka and Hiroyuki Daida and Yoshiki Egashira and Hideo Fujita and Jitsuo Higaki and Hirata, {Ken Ichi} and Shun Ishibashi and Takaaki Isshiki and Sadayoshi Ito and Atsunori Kashiwagi and Satoshi Kato and Kazuo Kitagawa and Masafumi Kitakaze and Takanari Kitazono and Masahiko Kurabayashi and Katsumi Miyauchi and Tomoaki Murakami and Toyoaki Murohara and Koichi Node and Susumu Ogawa and Yoshihiko Saito and Yoshihiko Seino and Takashi Shigeeda and Shunya Shindo and Masahiro Sugawara and Seigo Sugiyama and Yasuo Terauchi and Hiroyuki Tsutsui and Kenji Ueshima and Kazunori Utsunomiya and Masakazu Yamagishi and Tsutomu Yamazaki and Shoei Yo and Koutaro Yokote and Kiyoshi Yoshida and Michihiro Yoshimura and Nagahisa Yoshimura and Kazuwa Nakao and Ryozo Nagai",
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TY - JOUR

T1 - Intensive treat-to-target statin therapy in high-risk Japanese patients with hypercholesterolemia and diabetic retinopathy

T2 - Report of a randomized study

AU - Itoh, Hiroshi

AU - Komuro, Issei

AU - Takeuchi, Masahiro

AU - Akasaka, Takashi

AU - Daida, Hiroyuki

AU - Egashira, Yoshiki

AU - Fujita, Hideo

AU - Higaki, Jitsuo

AU - Hirata, Ken Ichi

AU - Ishibashi, Shun

AU - Isshiki, Takaaki

AU - Ito, Sadayoshi

AU - Kashiwagi, Atsunori

AU - Kato, Satoshi

AU - Kitagawa, Kazuo

AU - Kitakaze, Masafumi

AU - Kitazono, Takanari

AU - Kurabayashi, Masahiko

AU - Miyauchi, Katsumi

AU - Murakami, Tomoaki

AU - Murohara, Toyoaki

AU - Node, Koichi

AU - Ogawa, Susumu

AU - Saito, Yoshihiko

AU - Seino, Yoshihiko

AU - Shigeeda, Takashi

AU - Shindo, Shunya

AU - Sugawara, Masahiro

AU - Sugiyama, Seigo

AU - Terauchi, Yasuo

AU - Tsutsui, Hiroyuki

AU - Ueshima, Kenji

AU - Utsunomiya, Kazunori

AU - Yamagishi, Masakazu

AU - Yamazaki, Tsutomu

AU - Yo, Shoei

AU - Yokote, Koutaro

AU - Yoshida, Kiyoshi

AU - Yoshimura, Michihiro

AU - Yoshimura, Nagahisa

AU - Nakao, Kazuwa

AU - Nagai, Ryozo

PY - 2018/6/1

Y1 - 2018/6/1

N2 - 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± 13months. LDL-C at 36 months was 76.5± 21.6mg/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.

AB - 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± 13months. LDL-C at 36 months was 76.5± 21.6mg/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.

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U2 - 10.2337/dc17-2224

DO - 10.2337/dc17-2224

M3 - Article

VL - 41

SP - 1275

EP - 1284

JO - Diabetes Care

JF - Diabetes Care

SN - 1935-5548

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