Aggressive LDL-C Lowering and the Brain: Impact on Risk for Dementia and Hemorrhagic Stroke: A Scientific Statement From the American Heart Association

Arteriosclerosis Thrombosis and Vascular Biology, Journal Year: 2023, Volume and Issue: 43(10)

Published: Sept. 14, 2023

The objective of this scientific statement is to evaluate contemporary evidence that either supports or refutes the conclusion aggressive low-density lipoprotein cholesterol lowering lipid exerts toxic effects on brain, leading cognitive impairment dementia hemorrhagic stroke. writing group used literature reviews, references published clinical and epidemiology studies, public health guidelines, authoritative statements, expert opinion summarize existing identify gaps in current knowledge. Although some retrospective, case control, prospective longitudinal studies suggest statins are associated with dementia, preponderance observational data from randomized trials do not support conclusion. risk a stroke statin therapy patients without history cerebrovascular disease nonsignificant, achieving very low levels does increase risk. Data reflecting lipid-lowering treatment among robust require additional focused study.

Language: Английский

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Lipoprotein Apheresis: Current Recommendations for Treating Familial Hypercholesterolemia and Elevated Lipoprotein(a)

Current Atherosclerosis Reports, Journal Year: 2023, Volume and Issue: 25(7), P. 391 - 404

Published: June 5, 2023

Language: Английский

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PCSK9 inhibition with orally administered NNC0385-0434 in hypercholesterolaemia: a randomised, double-blind, placebo-controlled and active-controlled phase 2 trial

The Lancet Diabetes & Endocrinology, Journal Year: 2024, Volume and Issue: 12(3), P. 174 - 183

Published: Feb. 2, 2024

Language: Английский

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Low-Density Lipoprotein Cholesterol-Lowering Drugs: A Narrative Review

Journal of Clinical Medicine, Journal Year: 2024, Volume and Issue: 13(4), P. 943 - 943

Published: Feb. 7, 2024

The modern history of cholesterol-lowering drugs started in 1972 when Dr. Akira Endo identified an active compound (compactin) that inhibited cholesterol biosynthesis from the culture broth blue–green mold (Penicillium citrinum Pen-51). Since 1987, statins have represented milestone for treatment atherosclerotic cardiovascular disease. A new therapy hypercholesterolemia since discovery is ezetimibe, first and only agent inhibiting intestinal absorption. Ezetimibe was approved by FDA October 2002. year later, association between gain-of-function PCSK9 genetic mutations reported, this opened a era lipid-lowering therapies. Monoclonal antibodies small-interfering RNA approaches to reduce were developed clinical use 2015 2022, respectively. Finally, newly bempedoic acid, oral adenosine triphosphate citrate lyase inhibitor lowers LDL-C, able major adverse events both primary secondary prevention. In present narrative review, we summarize pharmacological properties efficacy all these agents currently used tailored patients with

Language: Английский

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Obicetrapib on top of maximally tolerated lipid‐modifying therapies in participants with or at high risk for atherosclerotic cardiovascular disease: rationale and designs of BROADWAY and BROOKLYN

American Heart Journal, Journal Year: 2024, Volume and Issue: 274, P. 32 - 45

Published: May 4, 2024

Obicetrapib, a novel, selective cholesteryl ester transfer protein (CETP) inhibitor, reduces low-density lipoprotein cholesterol (LDL-C), LDL particles, apolipoprotein (Apo) B, and lipoprotein(a) [Lp(a)] increases high-density (HDL-C) when added to statins with or without ezetimibe. By substantially reducing LDL-C, obicetrapib has the potential lower atherogenic lipoproteins in patients atherosclerotic cardiovascular disease (ASCVD) heterozygous familial hypercholesterolemia (HeFH) whose LDL-C levels remain high despite treatment available maximally tolerated lipid-modifying therapies, addressing an unmet medical need patient population at risk for events. BROADWAY (NCT05142722) BROOKLYN (NCT05425745) are ongoing placebo-controlled, double-blind, randomized Phase III trials designed examine efficacy, safety, tolerability of as adjunct dietary intervention therapies participants history ASCVD and/or underlying HeFH is not adequately controlled. The primary efficacy endpoint was percent change from baseline day 84. Other endpoints included changes Apo non-HDL-C, HDL-C, A1, Lp(a) triglycerides addition parameters evaluating tolerability, pharmacokinetics. also adjudicated assessment major adverse events, measurements glucose homeostasis, ambulatory blood pressure monitoring substudy. A total 2532 were 354 receive 10 mg placebo (2:1) 365 days follow-up through 35 after last dose. Results both anticipated 2024. These will provide safety data support use among elevated whom existing sufficiently effective well-tolerated.

Language: Английский

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Harnessing RNA Interference for Cholesterol Lowering: The Bench‐to‐Bedside Story of Inclisiran

Journal of the American Heart Association, Journal Year: 2024, Volume and Issue: 13(6)

Published: March 8, 2024

Lowering low-density lipoprotein cholesterol (LDL-C) is a cornerstone of reducing risk for atherosclerotic cardiovascular disease. Despite the approval nonstatin therapies LDL-C lowering over past 2 decades, these medications are underused, and most patients still not at guideline-recommended goals. Barriers include poor adherence, clinical inertia, concern side effects, cost, complex prior authorization processes. With disease-related mortality increasing globally, there remains need additional therapeutic options as part an disease prevention strategy. Following identification PCSK9 (proprotein convertase subtilisin/kexin type 9) promising target, inclisiran was developed using natural process RNA interference robust, sustained hepatic synthesis. Twice-yearly maintenance subcutaneous (following initial loading doses Day 1 90) reduces circulating levels by ≈50% versus placebo when added to maximally tolerated statins. Long-term safety tolerability have been assessed, with studies underway evaluate effects on outcomes provide effectiveness data. In 2021, <20 years after discovery PCSK9, became first approved in United States established or familial hypercholesterolemia has since use primary hyperlipidemia. This article reviews journey from bench bedside, including early development, trial program, key characteristics inclisiran, practical points its clinic.

Language: Английский

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Managing Hypercholesterolemia in Adults Older Than 75 years Without a History of Atherosclerotic Cardiovascular Disease: An Expert Clinical Consensus From the National Lipid Association and the American Geriatrics Society

Journal of the American Geriatrics Society, Journal Year: 2025, Volume and Issue: unknown

Published: April 10, 2025

ABSTRACT The risk of atherosclerotic cardiovascular disease increases with advancing age. Elevated LDL‐cholesterol and non‐HDL‐cholesterol levels remain predictive incident events among individuals older than 75 years. Risk prediction is less certain because most current calculators lack specificity in those years do not adjust for co‐morbidities, functional status, frailty, cognition which significantly impact prognosis this age group. Data on the benefits risks lowering statins patients without are also limited since primary prevention trials have included mostly younger patients. Available data suggest that statin therapy may reduce from lipid‐lowering outweigh potential such as statin‐associated muscle symptoms Type 2 diabetes mellitus. While some evidence suggests possibility be associated cognitive impairment adults, a preponderance literature indicates neutral or even protective statin‐related effects. Shared decision‐making recommended all when considering particularly important Randomized clinical trial evaluating use non‐statin sparse. Deprescribing agents appropriate select life‐limiting diseases. Finally, patient‐centered approach should taken strategies adults.

Language: Английский

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Red Yeast Rice for the Improvement of Lipid Profiles in Mild-to-Moderate Hypercholesterolemia: A Narrative Review

Nutrients, Journal Year: 2023, Volume and Issue: 15(10), P. 2288 - 2288

Published: May 12, 2023

Reducing low-density lipoprotein cholesterol (LDL-C) levels is a key target for lowering cardiovascular risk and preventing atherosclerotic disease (ASCVD). Red yeast rice (RYR) nutraceutical widely used as lipid-lowering dietary supplement. The main cholesterol-lowering components of RYR are monacolins, particularly monacolin K, which structurally identical to lovastatin targets the same enzyme biosynthesis. supplementation reduces LDL-C by approximately 15–34% versus placebo, with similar effect low-dose, first-generation statins in subjects mild-to-moderate dyslipidemia. has also demonstrated beneficial reductions up 45% placebo ASCVD events secondary prevention studies. at dose that provides about 3 mg/d K well tolerated, an adverse event profile low-dose statins. therefore treatment option people hypercholesterolemia who ineligible statin therapy, those unable implement lifestyle modifications, eligible therapy but unwilling take pharmacologic therapy.

Language: Английский

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Advances in treatment strategies based on scavenging reactive oxygen species of nanoparticles for atherosclerosis

Journal of Nanobiotechnology, Journal Year: 2023, Volume and Issue: 21(1)

Published: Aug. 17, 2023

Abstract The development of atherosclerosis (AS) is closely linked to changes in the plaque microenvironment, which consists primarily cells that form and associated factors they secrete. onset inflammation, lipid deposition, various pathological cellular metabolism accompany microenvironment will promote AS. Numerous studies have shown oxidative stress an important condition promotes accumulation reactive oxygen species (ROS) stress’s most change. In turn, effects ROS on are complex varied, these ultimately reflected promotion or inhibition This article reviews atherosclerotic plaques their impact disease progression over past five years focuses progress treatment strategies based scavenging nanoparticles for Finally, we also discuss prospects challenges AS treatment.

Language: Английский

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Management of Statin Intolerant Patients in the Era of Novel Lipid Lowering Therapies: A Critical Approach in Clinical Practice

Journal of Clinical Medicine, Journal Year: 2023, Volume and Issue: 12(6), P. 2444 - 2444

Published: March 22, 2023

Statins are the cornerstone of lipid-lowering therapies effective for cardiovascular risk reduction. Although they generally well tolerated, statin intolerance (SI) is frequent in clinical practice, and it usually related to onset muscle symptoms, which defined under acronym SAMS (Statin-Associated Muscle Side Effects). These side effects responsible treatment discontinuation that results increased risk. The National Lipid Association (NLA) has recently provided an updated definition intolerance, a distinction between complete partial been reported. evaluation symptom severity presence damage biomarker alterations make essential adopt patient-centered approach aimed at obtaining personalized therapeutic strategy. Firstly, could be useful administer different statin, reduce dosage or alternate regimen. However, some patients unable tolerate any every dosage, despite taking statins maximum tolerated dose, fail achieve recommended LDL-C target, thus necessary introduce non-statin hypolipidemic treatment. Ezetimibe, proprotein-convertase subtilisin/kexin type 9 (PCSK9) inhibitors such as monoclonal antibodies (alirocumab evolocumab) RNA messenger silencing (inclisiran), bempedoic acid nutraceuticals used alternative addition early sustained reduction practice. In this review, we evaluated SI management focusing on lipid lowering their implications approaches

Language: Английский

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