Pemafibrate Prevents Rupture of Angiotensin II-Induced Abdominal Aortic Aneurysms

Amioka, Naofumi; Miyoshi, Toru; Yonezawa, Tomoko; Kondo, Megumi; Akagi, Satoshi; Yoshida, Masashi; Saito, Yukihiro; Nakamura, Kazufumi; Ito, Hiroshi

doi:10.3389/fcvm.2022.904215

Cited by 6 publications

(5 citation statements)

References 67 publications

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“…However, as there is a residual cardiovascular risk caused mainly by high triglyceride and low HDL-cholesterol levels, the addition of fibrates to statin monotherapy may benefit patients at residual risk [ 30 , 37 , 38 ]. Recent studies in animal models have linked pemafibrate to a reduction in the risk of abdominal aortic aneurysm rupture, but further studies are needed to confirm this [ 39 ]. Although great expectations have been placed on pemafibrate, a selective peroxisome proliferator-activated receptor alpha modulator (SPPARMα) [ 39 , 40 ], the PROMINENT trial of this drug failed to show a reduction in the incidence of cardiovascular events in patients with type 2 diabetes and dyslipidaemia, although pemafibrate did lower triglycerides, VLDL-cholesterol, residual cholesterol and apolipoprotein C III [ 41 ].…”

Section: Present Therapeutic Optionsmentioning

confidence: 99%

Present and Future of Dyslipidaemia Treatment—A Review

Merćep,

Vujević,

Strikić

et al. 2023

JCM

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One of the greatest burdens on the healthcare systems of modern civilization is cardiovascular diseases (CVDs). Therefore, the medical community is looking for ways to reduce the incidence of CVDs. Simple lifestyle changes from an unhealthy to a healthy lifestyle are the cornerstone of prevention, but other risk factors for cardiovascular disease are also being currently targeted, most notably dyslipidaemia. It is well known that lowering serum lipid levels, and in particular lowering elevated LDL-cholesterol, leads to a reduction in major cardiovascular events. Although the focus to date has been on LDL-cholesterol levels and lowering them with statin therapy, this is often not enough because of increased concentrations of other lipoprotein particles in the serum and residual cardiovascular risk. Since lowering LDL-cholesterol levels is successful in most cases, there has been a recent focus on lowering residual cardiovascular risk. In recent years, new therapeutic options have emerged that target triglyceride-rich lipoproteins, lipoprotein (a) and apolipoproteins C and B. The effects of these drugs on serious adverse cardiovascular events are not yet known, but recent studies with some of these drugs have shown significant results in lowering total lipid levels. The aim of this review is to present the current therapeutic options for the treatment of dyslipidaemia and to describe the newly approved drugs as well as the drugs that are still in development. Although at this stage we cannot say with certainty whether these agents will be approved and widely used, it is safe to say that our views on the treatment of dyslipidaemia are certainly changing.

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Section: Present Therapeutic Optionsmentioning

confidence: 99%

Present and Future of Dyslipidaemia Treatment—A Review

Merćep,

Vujević,

Strikić

et al. 2023

JCM

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“…This effect may be particularly beneficial for individuals with diabetic kidney disease. In experimental mouse models, pemafibrate has been reported to reduce oxidative stress and prevent the rupture of abdominal aortic aneurysms 13) . Significance of hypertriglyceridemia in secondary prevention of coronary artery disease Many reports have shown that high TG levels in the general population are associated with a higher incidence of CAD [1][2][3] .…”

Section: Benefi Ts Of Pemafi Brate Including Effects Other Than Tglow...mentioning

confidence: 99%

Pemafibrate Effectively Reduced Triglycerides in Patients with a History of PCI or CABG

Itoh,

Shimura,

Nakatsuji

2024

Journal of Coronary Artery Disease

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Strict control of low-density lipoprotein cholesterol (LDL) levels is important for secondary prevention of angina pectoris and acute myocardial infarction; although it may not be as important as LDL levels, high plasma triglyceride (TG) levels have also been reported to be a risk factor for secondary coronary events [1][2][3] . Given that LDL can be adequately controlled with statins, ezetimibe, and PCSK9 inhibitors, treatment of the remaining risk factor, hypertriglyceridemia, is considered important. We report the results of a 2-year follow-up study of lipid levels in high-risk patients with dyslipidemia, a history of coronary artery disease (CAD), and previous percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). Patients and methodsThe study was conducted in accordance with the Declaration of Helsinki and the research protocol was approved by the ethics committee of the institution.Forty-six patients (male, n = 38; female, n = 8; mean age 68 years) with a history of angina pectoris or myocardial infarction and a TG concentration of 150 mg/dl or higher in an ambulatory blood draw were included. According to the 2017 Japan Atherosclerosis Society (JAS) guidelines, hypertriglyceridemia was defined only as a fasting level ≥ 150 mg/dl. The 2022 guidelines defi ne hypertriglyceridemia as a fasting level of ≥ 150 mg/dl and a level of ≥ 175 mg/dl at any time of day. Because this study began prior to the issuance of the 2022 guidelines and due to the fact that several patients did not undergo strict fasting blood draws, the criterion of 150 mg/dl or higher was utilized.

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“…Pemafibrate reversed the enhanced neutrophil adhesion on the atheroprone femoral artery of high-fat diet-fed LDL receptor knockout mice caused by histone H3 citrullination [ 107 ]. It also prevented AAA rupture in apo E-null mice induced by subcutaneous infusion of angiotensin II [ 108 ]. This pemafibrate effect was associated with a reduction in reactive oxygen species, extracellular matrix degradation, and inflammation in the aortic wall.…”

Section: Effects Of Pemafibrate On Endothelial Function Neointimal Fo...mentioning

confidence: 99%

Novel Selective PPARα Modulator Pemafibrate for Dyslipidemia, Nonalcoholic Fatty Liver Disease (NAFLD), and Atherosclerosis

Yamashita¹,

Rizzo

et al. 2023

Metabolites

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Statins, the intestinal cholesterol transporter inhibitor (ezetimibe), and PCSK9 inhibitors can reduce serum LDL-C levels, leading to a significant reduction in cardiovascular events. However, these events cannot be fully prevented even when maintaining very low LDL-C levels. Hypertriglyceridemia and reduced HDL-C are known as residual risk factors for ASCVD. Hypertriglyceridemia and/or low HDL-C can be treated with fibrates, nicotinic acids, and n-3 polyunsaturated fatty acids. Fibrates were demonstrated to be PPARα agonists and can markedly lower serum TG levels, yet were reported to cause some adverse effects, including an increase in the liver enzyme and creatinine levels. Recent megatrials of fibrates have shown negative findings on the prevention of ASCVD, which were supposed to be due to their low selectivity and potency for binding to PPAR α. To overcome the off-target effects of fibrates, the concept of a selective PPARα modulator (SPPARMα) was proposed. Kowa Company, Ltd. (Tokyo, Japan), has developed pemafibrate (K-877). Compared with fenofibrate, pemafibrate showed more favorable effects on the reduction of TG and an increase in HDL-C. Fibrates worsened liver and kidney function test values, although pemafibrate showed a favorable effect on liver function test values and little effect on serum creatinine levels and eGFR. Minimal drug–drug interactions of pemafibrate with statins were observed. While most of the fibrates are mainly excreted from the kidney, pemafibrate is metabolized in the liver and excreted into the bile. It can be used safely even in patients with CKD, without a significant increase in blood concentration. In the megatrial of pemafibrate, PROMINENT, for dyslipidemic patients with type 2 diabetes, mild-to-moderate hypertriglyceridemia, and low HDL-C and LDL-C levels, the incidence of cardiovascular events did not decrease among those receiving pemafibrate compared to those receiving the placebo; however, the incidence of nonalcoholic fatty liver disease was lower. Pemafibrate may be superior to conventional fibrates and applicable to CKD patients. This current review summarizes the recent findings on pemafibrate.

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Pemafibrate Prevents Rupture of Angiotensin II-Induced Abdominal Aortic Aneurysms

Cited by 6 publications

References 67 publications

Present and Future of Dyslipidaemia Treatment—A Review

Present and Future of Dyslipidaemia Treatment—A Review

Pemafibrate Effectively Reduced Triglycerides in Patients with a History of PCI or CABG

Novel Selective PPARα Modulator Pemafibrate for Dyslipidemia, Nonalcoholic Fatty Liver Disease (NAFLD), and Atherosclerosis

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