Evinacumab in severe hypertriglyceridemia with or without lipoprotein lipase pathway mutations: a phase 2 randomized trial

Nature Medicine, Год журнала: 2023, Номер 29(3), С. 729 - 737

Опубликована: Март 1, 2023

Severe hypertriglyceridemia (sHTG) is an established risk factor for acute pancreatitis. Current therapeutic approaches sHTG are often insufficient to reduce triglycerides and prevent This phase 2 trial ( NCT03452228 ) evaluated evinacumab (angiopoietin-like 3 inhibitor) in three cohorts of patients with sHTG: cohort 1, familial chylomicronemia syndrome bi-allelic loss-of-function lipoprotein lipase (LPL) pathway mutations (n = 17); 2, multifactorial heterozygous LPL 15); 3, without 19). Fifty-one (males, n 27; females, 24) a history hospitalization pancreatitis were randomized 2:1 intravenous 15 mg kg

Язык: Английский

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There is urgent need to treat atherosclerotic cardiovascular disease risk earlier, more intensively, and with greater precision: A review of current practice and recommendations for improved effectiveness

American Journal of Preventive Cardiology, Год журнала: 2022, Номер 12, С. 100371 - 100371

Опубликована: Авг. 6, 2022

Atherosclerotic cardiovascular disease (ASCVD) is epidemic throughout the world and etiologic for such acute events as myocardial infarction, ischemic stroke, unstable angina, death. ASCVD also impacts risk dementia, chronic kidney peripheral arterial mobility, impaired sexual response, a host of other visceral impairments that adversely impact quality rate progression aging. The relationship between low-density lipoprotein cholesterol (LDL-C) one most highly established investigated issues in entirety modern medicine. Elevated LDL-C necessary condition atherogenesis induction. Basic scientific investigation, prospective longitudinal cohorts, randomized clinical trials have all validated this association. Yet despite enormous number which support need reducing burden atherogenic blood, percentage high very high-risk patients who achieve stratified target reductions low has remained last thirty years. Atherosclerosis preventable disease. As clinicians, time come us to take primordial primary prevention more serously. Despite plethora therapeutic approaches, large majority at are poorly or inadequately treated, leaving them vulnerable progression, events, poor aging due loss function multiple organs. Herein we discuss greatly intensify efforts reduce risk, decrease burden, provide comprehensive earlier assessment optimally prevent its complications. Evidence presented treatment should aim far lower goals management, into account many factors than commonly employed today begin significantly life.

Язык: Английский

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New Therapies for Lowering Triglyceride-Rich Lipoproteins

Journal of the American College of Cardiology, Год журнала: 2021, Номер 78(18), С. 1817 - 1830

Опубликована: Окт. 25, 2021

Язык: Английский

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Clinical Trial Design for Triglyceride-Rich Lipoprotein-Lowering Therapies

Journal of the American College of Cardiology, Год журнала: 2023, Номер 81(16), С. 1646 - 1658

Опубликована: Апрель 1, 2023

Язык: Английский

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Severe hypertriglyceridemia: Existing and emerging therapies

Pharmacology & Therapeutics, Год журнала: 2023, Номер 251, С. 108544 - 108544

Опубликована: Окт. 15, 2023

Язык: Английский

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Evinacumab Reduces Triglyceride-Rich Lipoproteins in Patients with Hyperlipidemia: A Post-Hoc Analysis of Three Randomized Clinical Trials

Cardiovascular Drugs and Therapy, Год журнала: 2024, Номер unknown

Опубликована: Март 6, 2024

Abstract Purpose Natural selection (Mendelian randomization) studies support a causal relationship between elevated triglyceride-rich lipoproteins (TRLs) and atherosclerotic cardiovascular disease (ASCVD). This post-hoc analysis assessed the efficacy of evinacumab in reducing TRLs patient cohorts from three separate clinical trials with evinacumab. Methods Patients homozygous familial hypercholesterolemia (HoFH) low-density lipoprotein cholesterol (LDL-C) ≥ 70 mg/dL were enrolled phase III trial (R1500-CL-1629; NCT03399786). diagnosed refractory hypercholesterolemia, LDL-C or 100 for those without ASCVD, respectively, II (R1500-CL-1643; NCT03175367). severe hypertriglyceridemia (fasting TGs 500 mg/dL) (R1500-HTG-1522; NCT03452228). received intravenously (5 15 mg/kg) every 4 weeks, subcutaneously (300 450 mg) week 2 weeks. Efficacy outcomes included change (calculated as total minus high-density LDL-C) other lipid parameters baseline to 12, 16, 24 weeks 1522, 1643, 1629, respectively. Results At baseline, TRL levels higher patients entering 1522 vs. cohorts. Reductions observed across all evinacumab, > 50% reduction at highest doses evaluated HoFH hypercholesterolemia. Within trials, was generally well tolerated. Conclusions Despite limitations direct comparisons study groups, these data indicate that could be future target lipid-lowering therapies.

Язык: Английский

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Associations of body mass index and remnant cholesterol with hyperuricemia in patients with hypertension

BMC Endocrine Disorders, Год журнала: 2025, Номер 25(1)

Опубликована: Март 18, 2025

There is a paucity of prior research on residual cholesterol (RC) and hyperuricemia, it remains unclear whether body mass index (BMI) functions as mediating factor between them or intensifies lipid metabolic dysregulation, thereby elevating the risk hyperuricemia. This study aims to investigate BMI mediates association RC well interaction joint effect cross-sectional study, involving total 14,218 hypertensive patients. Exposure factors include BMI. The outcome was Hyperuricemia, defined serum uric acid (SUA) ≥ 420 µmol/L. Multivariable logistic regression models causal mediation analysis were used examine prevalence A patients enrolled in this comprising 6,713 (47.2%) males, with mean age 63.8 (9.36) years. diabetes mellitus found be 10.4% (1,473), while hyperuricemia accounted for approximately 44.4% (6,319). results show that there linear positive correlation (P trend < 0.01). only had significant additive but no multiplicative (Additive: RERI = 0.45, 95%CI: 0.13-0.78; Multiplicative, OR 1.09, 95% CI 0.92-1.3, P 0.308). are direct indirect effects [estimate (95% CI): DE 0.063 (0.048, 0.070), IE 0.005 (0.003, 0.001)]. In aforementioned analysis, among caused by RC, 7.1%. intermediary role its play pivotal augmenting Registered prospectively Chinese Clinical Trial Registry (ChiCTR1800017274) July 20, 2018. Access at https://www.chictr.org.cn/showproj.html?proj=28262 .

Язык: Английский

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The Novel Lipid-Based Chronic Disease Model in Lifestyle Medicine: Impact on Prevention of Atherosclerotic Cardiovascular Disease

Lifestyle Medicine, Год журнала: 2025, Номер unknown, С. 75 - 102

Опубликована: Янв. 1, 2025

Язык: Английский

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The Emerging Potential of Apolipoprotein C-III Inhibition for ASCVD Prevention: A State-of-the-Art Review

Current Atherosclerosis Reports, Год журнала: 2024, Номер 27(1)

Опубликована: Ноя. 14, 2024

Язык: Английский

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Is Apo-CIII the new cardiovascular target? An analysis of its current clinical and dietetic therapies

Nutrition Metabolism and Cardiovascular Diseases, Год журнала: 2021, Номер 32(2), С. 295 - 308

Опубликована: Окт. 13, 2021

Язык: Английский

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