High-dose versus low-dose pitavastatin in Japanese patients with stable coronary artery disease (REAL-CAD) a randomized superiority trial

Isao Taguchi, Satoshi Iimuro, Hiroshi Iwata, Hiroaki Takashima, Mitsuru Abe, Eisuke Amiya, Takanori Ogawa, Yukio Ozaki, Ichiro Sakuma, Yoshihisa Nakagawa, Kiyoshi Hibi, Takafumi Hiro, Yoshihiro Fukumoto, Seiji Hokimoto, Katsumi Miyauchi, Tsutomu Yamazaki, Hiroshi Ito, Yutaka Otsuji, Kazuo Kimura, Jun TakahashiAtsushi Hirayama, Hiroyoshi Yokoi, Kazuo Kitagawa, Takao Urabe, Yasushi Okada, Yasuo Terayama, Kazunori Toyoda, Takehiko Nagao, Masayasu Matsumoto, Yasuo Ohashi, Tetsuji Kaneko, Retsu Fujita, Hiroshi Ohtsu, Hisao Ogawa, Hiroyuki Daida, Hiroaki Shimokawa, Yasushi Saito, Takeshi Kimura, Teruo Inoue, Masunori Matsuzaki, Ryozo Nagai

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

BACKGROUND: Current guidelines call for high-intensity statin therapy in patients with cardiovascular disease on the basis of several previous “more versus less statins” trials. However, no clear evidence for more versus less statins has been established in an Asian population. METHODS: In this prospective, multicenter, randomized, open-label, blinded end point study, 13054 Japanese patients with stable coronary artery disease who achieved low-density lipoprotein cholesterol (LDL-C) <120 mg/dL during a run-in period (pitavastatin 1 mg/d) were randomized in a 1-to-1 fashion to high-dose (pitavastatin 4 mg/d; n=6526) or low-dose (pitavastatin 1 mg/d; n=6528) statin therapy. The primary end point was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal ischemic stroke, or unstable angina requiring emergency hospitalization. The secondary composite end point was a composite of the primary end point and clinically indicated coronary revascularization excluding target-lesion revascularization at sites of prior percutaneous coronary intervention. RESULTS: The mean age of the study population was 68 years, and 83% were male. The mean LDL-C level before enrollment was 93 mg/dL with 91% of patients taking statins. The baseline LDL-C level after the run-in period on pitavastatin 1 mg/d was 87.7 and 88.1 mg/dL in the high-dose and low-dose groups, respectively. During the entire course of follow-up, LDL-C in the high-dose group was lower by 14.7 mg/ dL than in the low-dose group (P<0.001). With a median follow-up of 3.9 years, high-dose as compared with low-dose pitavastatin significantly reduced the risk of the primary end point (266 patients [4.3%] and 334 patients [5.4%]; hazard ratio, 0.81; 95% confidence interval, 0.69–0.95; P=0.01) and the risk of the secondary composite end point (489 patients [7.9%] and 600 patients [9.7%]; hazard ratio, 0.83; 95% confidence interval, 0.73–0.93; P=0.002). High-dose pitavastatin also significantly reduced the risks of several other secondary end points such as all-cause death, myocardial infarction, and clinically indicated coronary revascularization. The results for the primary and the secondary composite end points were consistent across several prespecified subgroups, including the low (<95 mg/dL) baseline LDL-C subgroup. Serious adverse event rates were low in both groups. CONCLUSIONS: High-dose (4 mg/d) compared with low-dose (1 mg/d) pitavastatin therapy significantly reduced cardiovascular events in Japanese patients with stable coronary artery disease.

Original languageEnglish
Pages (from-to)1997-2009
Number of pages13
JournalCirculation
Volume137
Issue number19
DOIs
Publication statusPublished - 01-01-2018

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Coronary Artery Disease
Hydroxymethylglutaryl-CoA Reductase Inhibitors
LDL Cholesterol
Myocardial Infarction
Confidence Intervals
pitavastatin
Unstable Angina
Percutaneous Coronary Intervention
Population
Cause of Death
Hospitalization
Emergencies
Cardiovascular Diseases
Therapeutics
Stroke
Guidelines

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Taguchi, Isao ; Iimuro, Satoshi ; Iwata, Hiroshi ; Takashima, Hiroaki ; Abe, Mitsuru ; Amiya, Eisuke ; Ogawa, Takanori ; Ozaki, Yukio ; Sakuma, Ichiro ; Nakagawa, Yoshihisa ; Hibi, Kiyoshi ; Hiro, Takafumi ; Fukumoto, Yoshihiro ; Hokimoto, Seiji ; Miyauchi, Katsumi ; Yamazaki, Tsutomu ; Ito, Hiroshi ; Otsuji, Yutaka ; Kimura, Kazuo ; Takahashi, Jun ; Hirayama, Atsushi ; Yokoi, Hiroyoshi ; Kitagawa, Kazuo ; Urabe, Takao ; Okada, Yasushi ; Terayama, Yasuo ; Toyoda, Kazunori ; Nagao, Takehiko ; Matsumoto, Masayasu ; Ohashi, Yasuo ; Kaneko, Tetsuji ; Fujita, Retsu ; Ohtsu, Hiroshi ; Ogawa, Hisao ; Daida, Hiroyuki ; Shimokawa, Hiroaki ; Saito, Yasushi ; Kimura, Takeshi ; Inoue, Teruo ; Matsuzaki, Masunori ; Nagai, Ryozo. / High-dose versus low-dose pitavastatin in Japanese patients with stable coronary artery disease (REAL-CAD) a randomized superiority trial. In: Circulation. 2018 ; Vol. 137, No. 19. pp. 1997-2009.
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title = "High-dose versus low-dose pitavastatin in Japanese patients with stable coronary artery disease (REAL-CAD) a randomized superiority trial",
abstract = "BACKGROUND: Current guidelines call for high-intensity statin therapy in patients with cardiovascular disease on the basis of several previous “more versus less statins” trials. However, no clear evidence for more versus less statins has been established in an Asian population. METHODS: In this prospective, multicenter, randomized, open-label, blinded end point study, 13054 Japanese patients with stable coronary artery disease who achieved low-density lipoprotein cholesterol (LDL-C) <120 mg/dL during a run-in period (pitavastatin 1 mg/d) were randomized in a 1-to-1 fashion to high-dose (pitavastatin 4 mg/d; n=6526) or low-dose (pitavastatin 1 mg/d; n=6528) statin therapy. The primary end point was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal ischemic stroke, or unstable angina requiring emergency hospitalization. The secondary composite end point was a composite of the primary end point and clinically indicated coronary revascularization excluding target-lesion revascularization at sites of prior percutaneous coronary intervention. RESULTS: The mean age of the study population was 68 years, and 83{\%} were male. The mean LDL-C level before enrollment was 93 mg/dL with 91{\%} of patients taking statins. The baseline LDL-C level after the run-in period on pitavastatin 1 mg/d was 87.7 and 88.1 mg/dL in the high-dose and low-dose groups, respectively. During the entire course of follow-up, LDL-C in the high-dose group was lower by 14.7 mg/ dL than in the low-dose group (P<0.001). With a median follow-up of 3.9 years, high-dose as compared with low-dose pitavastatin significantly reduced the risk of the primary end point (266 patients [4.3{\%}] and 334 patients [5.4{\%}]; hazard ratio, 0.81; 95{\%} confidence interval, 0.69–0.95; P=0.01) and the risk of the secondary composite end point (489 patients [7.9{\%}] and 600 patients [9.7{\%}]; hazard ratio, 0.83; 95{\%} confidence interval, 0.73–0.93; P=0.002). High-dose pitavastatin also significantly reduced the risks of several other secondary end points such as all-cause death, myocardial infarction, and clinically indicated coronary revascularization. The results for the primary and the secondary composite end points were consistent across several prespecified subgroups, including the low (<95 mg/dL) baseline LDL-C subgroup. Serious adverse event rates were low in both groups. CONCLUSIONS: High-dose (4 mg/d) compared with low-dose (1 mg/d) pitavastatin therapy significantly reduced cardiovascular events in Japanese patients with stable coronary artery disease.",
author = "Isao Taguchi and Satoshi Iimuro and Hiroshi Iwata and Hiroaki Takashima and Mitsuru Abe and Eisuke Amiya and Takanori Ogawa and Yukio Ozaki and Ichiro Sakuma and Yoshihisa Nakagawa and Kiyoshi Hibi and Takafumi Hiro and Yoshihiro Fukumoto and Seiji Hokimoto and Katsumi Miyauchi and Tsutomu Yamazaki and Hiroshi Ito and Yutaka Otsuji and Kazuo Kimura and Jun Takahashi and Atsushi Hirayama and Hiroyoshi Yokoi and Kazuo Kitagawa and Takao Urabe and Yasushi Okada and Yasuo Terayama and Kazunori Toyoda and Takehiko Nagao and Masayasu Matsumoto and Yasuo Ohashi and Tetsuji Kaneko and Retsu Fujita and Hiroshi Ohtsu and Hisao Ogawa and Hiroyuki Daida and Hiroaki Shimokawa and Yasushi Saito and Takeshi Kimura and Teruo Inoue and Masunori Matsuzaki and Ryozo Nagai",
year = "2018",
month = "1",
day = "1",
doi = "10.1161/CIRCULATIONAHA.117.032615",
language = "English",
volume = "137",
pages = "1997--2009",
journal = "Circulation",
issn = "0009-7322",
publisher = "Lippincott Williams and Wilkins",
number = "19",

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Taguchi, I, Iimuro, S, Iwata, H, Takashima, H, Abe, M, Amiya, E, Ogawa, T, Ozaki, Y, Sakuma, I, Nakagawa, Y, Hibi, K, Hiro, T, Fukumoto, Y, Hokimoto, S, Miyauchi, K, Yamazaki, T, Ito, H, Otsuji, Y, Kimura, K, Takahashi, J, Hirayama, A, Yokoi, H, Kitagawa, K, Urabe, T, Okada, Y, Terayama, Y, Toyoda, K, Nagao, T, Matsumoto, M, Ohashi, Y, Kaneko, T, Fujita, R, Ohtsu, H, Ogawa, H, Daida, H, Shimokawa, H, Saito, Y, Kimura, T, Inoue, T, Matsuzaki, M & Nagai, R 2018, 'High-dose versus low-dose pitavastatin in Japanese patients with stable coronary artery disease (REAL-CAD) a randomized superiority trial', Circulation, vol. 137, no. 19, pp. 1997-2009. https://doi.org/10.1161/CIRCULATIONAHA.117.032615

High-dose versus low-dose pitavastatin in Japanese patients with stable coronary artery disease (REAL-CAD) a randomized superiority trial. / Taguchi, Isao; Iimuro, Satoshi; Iwata, Hiroshi; Takashima, Hiroaki; Abe, Mitsuru; Amiya, Eisuke; Ogawa, Takanori; Ozaki, Yukio; Sakuma, Ichiro; Nakagawa, Yoshihisa; Hibi, Kiyoshi; Hiro, Takafumi; Fukumoto, Yoshihiro; Hokimoto, Seiji; Miyauchi, Katsumi; Yamazaki, Tsutomu; Ito, Hiroshi; Otsuji, Yutaka; Kimura, Kazuo; Takahashi, Jun; Hirayama, Atsushi; Yokoi, Hiroyoshi; Kitagawa, Kazuo; Urabe, Takao; Okada, Yasushi; Terayama, Yasuo; Toyoda, Kazunori; Nagao, Takehiko; Matsumoto, Masayasu; Ohashi, Yasuo; Kaneko, Tetsuji; Fujita, Retsu; Ohtsu, Hiroshi; Ogawa, Hisao; Daida, Hiroyuki; Shimokawa, Hiroaki; Saito, Yasushi; Kimura, Takeshi; Inoue, Teruo; Matsuzaki, Masunori; Nagai, Ryozo.

In: Circulation, Vol. 137, No. 19, 01.01.2018, p. 1997-2009.

Research output: Contribution to journalArticle

TY - JOUR

T1 - High-dose versus low-dose pitavastatin in Japanese patients with stable coronary artery disease (REAL-CAD) a randomized superiority trial

AU - Taguchi, Isao

AU - Iimuro, Satoshi

AU - Iwata, Hiroshi

AU - Takashima, Hiroaki

AU - Abe, Mitsuru

AU - Amiya, Eisuke

AU - Ogawa, Takanori

AU - Ozaki, Yukio

AU - Sakuma, Ichiro

AU - Nakagawa, Yoshihisa

AU - Hibi, Kiyoshi

AU - Hiro, Takafumi

AU - Fukumoto, Yoshihiro

AU - Hokimoto, Seiji

AU - Miyauchi, Katsumi

AU - Yamazaki, Tsutomu

AU - Ito, Hiroshi

AU - Otsuji, Yutaka

AU - Kimura, Kazuo

AU - Takahashi, Jun

AU - Hirayama, Atsushi

AU - Yokoi, Hiroyoshi

AU - Kitagawa, Kazuo

AU - Urabe, Takao

AU - Okada, Yasushi

AU - Terayama, Yasuo

AU - Toyoda, Kazunori

AU - Nagao, Takehiko

AU - Matsumoto, Masayasu

AU - Ohashi, Yasuo

AU - Kaneko, Tetsuji

AU - Fujita, Retsu

AU - Ohtsu, Hiroshi

AU - Ogawa, Hisao

AU - Daida, Hiroyuki

AU - Shimokawa, Hiroaki

AU - Saito, Yasushi

AU - Kimura, Takeshi

AU - Inoue, Teruo

AU - Matsuzaki, Masunori

AU - Nagai, Ryozo

PY - 2018/1/1

Y1 - 2018/1/1

N2 - BACKGROUND: Current guidelines call for high-intensity statin therapy in patients with cardiovascular disease on the basis of several previous “more versus less statins” trials. However, no clear evidence for more versus less statins has been established in an Asian population. METHODS: In this prospective, multicenter, randomized, open-label, blinded end point study, 13054 Japanese patients with stable coronary artery disease who achieved low-density lipoprotein cholesterol (LDL-C) <120 mg/dL during a run-in period (pitavastatin 1 mg/d) were randomized in a 1-to-1 fashion to high-dose (pitavastatin 4 mg/d; n=6526) or low-dose (pitavastatin 1 mg/d; n=6528) statin therapy. The primary end point was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal ischemic stroke, or unstable angina requiring emergency hospitalization. The secondary composite end point was a composite of the primary end point and clinically indicated coronary revascularization excluding target-lesion revascularization at sites of prior percutaneous coronary intervention. RESULTS: The mean age of the study population was 68 years, and 83% were male. The mean LDL-C level before enrollment was 93 mg/dL with 91% of patients taking statins. The baseline LDL-C level after the run-in period on pitavastatin 1 mg/d was 87.7 and 88.1 mg/dL in the high-dose and low-dose groups, respectively. During the entire course of follow-up, LDL-C in the high-dose group was lower by 14.7 mg/ dL than in the low-dose group (P<0.001). With a median follow-up of 3.9 years, high-dose as compared with low-dose pitavastatin significantly reduced the risk of the primary end point (266 patients [4.3%] and 334 patients [5.4%]; hazard ratio, 0.81; 95% confidence interval, 0.69–0.95; P=0.01) and the risk of the secondary composite end point (489 patients [7.9%] and 600 patients [9.7%]; hazard ratio, 0.83; 95% confidence interval, 0.73–0.93; P=0.002). High-dose pitavastatin also significantly reduced the risks of several other secondary end points such as all-cause death, myocardial infarction, and clinically indicated coronary revascularization. The results for the primary and the secondary composite end points were consistent across several prespecified subgroups, including the low (<95 mg/dL) baseline LDL-C subgroup. Serious adverse event rates were low in both groups. CONCLUSIONS: High-dose (4 mg/d) compared with low-dose (1 mg/d) pitavastatin therapy significantly reduced cardiovascular events in Japanese patients with stable coronary artery disease.

AB - BACKGROUND: Current guidelines call for high-intensity statin therapy in patients with cardiovascular disease on the basis of several previous “more versus less statins” trials. However, no clear evidence for more versus less statins has been established in an Asian population. METHODS: In this prospective, multicenter, randomized, open-label, blinded end point study, 13054 Japanese patients with stable coronary artery disease who achieved low-density lipoprotein cholesterol (LDL-C) <120 mg/dL during a run-in period (pitavastatin 1 mg/d) were randomized in a 1-to-1 fashion to high-dose (pitavastatin 4 mg/d; n=6526) or low-dose (pitavastatin 1 mg/d; n=6528) statin therapy. The primary end point was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal ischemic stroke, or unstable angina requiring emergency hospitalization. The secondary composite end point was a composite of the primary end point and clinically indicated coronary revascularization excluding target-lesion revascularization at sites of prior percutaneous coronary intervention. RESULTS: The mean age of the study population was 68 years, and 83% were male. The mean LDL-C level before enrollment was 93 mg/dL with 91% of patients taking statins. The baseline LDL-C level after the run-in period on pitavastatin 1 mg/d was 87.7 and 88.1 mg/dL in the high-dose and low-dose groups, respectively. During the entire course of follow-up, LDL-C in the high-dose group was lower by 14.7 mg/ dL than in the low-dose group (P<0.001). With a median follow-up of 3.9 years, high-dose as compared with low-dose pitavastatin significantly reduced the risk of the primary end point (266 patients [4.3%] and 334 patients [5.4%]; hazard ratio, 0.81; 95% confidence interval, 0.69–0.95; P=0.01) and the risk of the secondary composite end point (489 patients [7.9%] and 600 patients [9.7%]; hazard ratio, 0.83; 95% confidence interval, 0.73–0.93; P=0.002). High-dose pitavastatin also significantly reduced the risks of several other secondary end points such as all-cause death, myocardial infarction, and clinically indicated coronary revascularization. The results for the primary and the secondary composite end points were consistent across several prespecified subgroups, including the low (<95 mg/dL) baseline LDL-C subgroup. Serious adverse event rates were low in both groups. CONCLUSIONS: High-dose (4 mg/d) compared with low-dose (1 mg/d) pitavastatin therapy significantly reduced cardiovascular events in Japanese patients with stable coronary artery disease.

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