Low-density lipoprotein cholesterol targeting with pitavastatin + ezetimibe for patients with acute coronary syndrome and dyslipidaemia: the HIJ-PROPER study, a prospective, open-label, randomized trial

Hagiwara, Nobuhisa; Kawada-Watanabe, Erisa; Koyanagi, Ryo; Arashi, Hiroyuki; Yamaguchi, Junichi; Nakao, Kōichi; Tobaru, Tetsuya; Tanaka, Hiroyuki; Oka, Takahiro; Endoh, Yasuhiro; Saito, Katsumi; Uchida, Tatsuo; Matsui, Kunihiko; Ogawa, Hiroshi

doi:10.1093/eurheartj/ehx162

Cited by 106 publications

(89 citation statements)

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“…Further studies with larger sample sizes are needed to elucidate this issue. On the other hand, a recent clinical trial has shown that serum sitosterol level could be a good biomarker of ezetimibe efficacy 24 ) . Serum sitosterol has been shown as a surrogate marker of cholesterol absorption 25 ) .…”

Section: Sitosterol or Cholesterol?mentioning

confidence: 99%

Sitosterolemia, Hypercholesterolemia, and Coronary Artery Disease

Tada

Nohara

Inazu

et al. 2018

J Atheroscler Thromb

101

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Sitosterolemia is a rare inherited disease characterized by increased levels of plant sterols, such as sitosterol. The cause of this disease is ATP-binding cassette (ABC) subfamily G member 5 or member 8 (ABCG5 or ABCG8, respectively) gene mutations. Recent advances in genetics have revealed that the prevalence of subjects with deleterious mutations in ABCG5 and/or ABCG8 genes could be more than 1 in ∼200,000 individuals among the general population. Furthermore, accumulated evidence, including infantile cases exhibiting progression/regression of systemic xanthomas associated with LDL cholesterol levels, have shown that the elevation of LDL cholesterol seems to be the major cause of development of atherosclerosis and not the elevation of sitosterol. Regarding therapies, LDL apheresis, as well as proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, could be useful for sitosterolemia, in addition to ezetimibe and/or colestimide. In this study, we provide the current understanding and future perspectives of sitosterolemia, which is currently considered an extremely rare disorder but is expected to be much more prevalent in clinical settings.

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Section: Sitosterol or Cholesterol?mentioning

confidence: 99%

Sitosterolemia, Hypercholesterolemia, and Coronary Artery Disease

Tada

Nohara

Inazu

et al. 2018

J Atheroscler Thromb

101

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“…Ezetimibe is one of the appropriate drug therapies for patients with sitosterolemia 4,9,10) . A recent study, the Heart Institute of Japan-PRoper level of lipid lOwering with Pitavastatin and Ezetimibe in acute coRonary syndrome (HIJ-PROPER), has shown that serum sitosterol level, which is a surrogate marker of cholesterol absorption, can be a good biomarker for CHD prevention efficacy under ezetimibe therapy 11) . In a sub-analysis of HIJ-PROPER, the aggressive lipid-lowering treatment with ezetimibe had a preven-shown).…”

Section: Introductionmentioning

confidence: 99%

Reference Intervals of Serum Non-Cholesterol Sterols by Gender in Healthy Japanese Individuals

Yoshida

Tada

Ito³

et al. 2020

JAT

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The present study was conducted to establish a practical method for measuring non-cholesterol sterols and reference intervals of serum levels. Methods: Healthy subjects (109 men and 151 women), four patients with sitosterolemia, and 10 heterozygous mutation carriers of ABCG5/ABCG8 genes were investigated. Then, three non-cholesterol sterols (sitosterol, campesterol, and lathosterol) of fasting serum samples were measured via a practical and highly sensitive gas chromatography (GC) method with 0.2 µg/mL as the lower limit of quantification. The coefficient of variation (CV) values for within-run reproducibility were 3.06%, 1.89%, and 1.77% for lathosterol, campesterol, and sitosterol, respectively. The CV values for between-run reproducibility were 2.81%, 2.06%, and 2.10% for lathosterol, campesterol, and sitosterol, respectively. Results: The serum levels of sitosterol and campesterol were significantly higher in women than in men, whereas the serum levels of lathosterol were significantly higher in men than in women. Because of these gender difference, the determination of reference intervals of the three sterol values was performed by considering gender. The reference intervals of sitosterol, campesterol, and lathosterol were 0.99-3.88, 2.14-7.43, and 0.77-3.60 µg/mL in men and 1.03-4.45, 2.19-8.34, and 0.64-2.78 µg/mL in women, respectively. The serum levels of sitosterol and campesterol were higher in patients with sitosterolemia (94.3 47.3 and 66.3 36.6 µg/mL, respectively) than in healthy subjects. Conclusion: These results demonstrate a practical and highly sensitive GC method to measure non-cholesterol sterol levels and gender-segregated reference intervals of sitosterol, campesterol, and lathosterol in Japanese healthy subjects.

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“…The lipid management strategy for secondary prevention is still changing in clinical practice from recent Japanese evidence. 21) REAL-CAD 22) Intervention…”

Section: Resultsmentioning

confidence: 99%

“…Recently two major outcome trials were reported from Japan. The HIJ-PROPER 21) study is a prospective, randomized, openlabel trial to assess whether intensive LDL-C lowering with standard-dose pitavastatin plus ezetimibe reduces cardiovascular events more than standard LDL-C lowering with pitavastatin monotherapy in patients with ACS and dyslipidaemia. Patients were randomized to intensive lowering (target LDL-C < 70 mg/dl); pitavastatin plus ezetimibe) or standard lowering (target LDL-C 90 mg/dl to 100 mg/dl); pitavastatin monotherapy).…”

Section: Clinical Evidence Of Aggressive Lipid Lowering In Secondarymentioning

confidence: 99%

The Role of Aggressive Lipid Lowering Therapy for Coronary Artery Disease

Daida

Fukushima

Ohmura

2019

Juntendo Medical Journal

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Atherosclerotic cardiovascular disease is the leading cause of death worldwide. Among the most promising results of the preventing approach against progression of atherosclerosis derived from lipid lowering therapy especially by statins. Recent clinical trials with statins indicated that aggressive lipid lowering therapy could inhibit the progression of atherosclerosis or even induce the regression of atherosclerotic plaque. It also stabilizes the unstable plaque to stable form and reduces clinical CV events.Several trials using intravascular ultrasound demonstrated that lowering LDL-C to 70-80 mg/dl by aggressive lipid-lowering treatment with moderately high-dose statins significantly reduced coronary plaque volume, but these studies are vastly underpowered to determine the effects of such lipid-lowering treatment on clinical outcomes. Accordingly, the value of reducing LDL-C levels substantially below 100 mg/dl in patients with CAD, particularly Asian patients, had not been clearly demonstrated, and Japanese guidelines recommended reducing LDL-C only to immediately below 100 mg/dl until recently. HIJ-PROPER and REAL-CAD provided pivotal evidence for the aggressive lipid-lowering in Japanese patients at secondary prevention. The lipid management strategy for secondary prevention is still changing in clinical practice from recent Japanese evidence.In this article, we will review the history and current understanding of the efficacy of aggressive lipid lowering therapy which inhibits the atherosclerosis progression and induces the regression, and we also will review the recent clinical evidence especially from Japan.

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Low-density lipoprotein cholesterol targeting with pitavastatin + ezetimibe for patients with acute coronary syndrome and dyslipidaemia: the HIJ-PROPER study, a prospective, open-label, randomized trial

Cited by 106 publications

References 50 publications

Sitosterolemia, Hypercholesterolemia, and Coronary Artery Disease

Sitosterolemia, Hypercholesterolemia, and Coronary Artery Disease

Reference Intervals of Serum Non-Cholesterol Sterols by Gender in Healthy Japanese Individuals

The Role of Aggressive Lipid Lowering Therapy for Coronary Artery Disease

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