etc-1002 and Coronary-Artery-Disease

Many patients do not achieve optimal low-density lipoprotein cholesterol (LDL-C) levels with statins alone; others are unable to tolerate statin therapy. Additional non-statin treatment options including ezetimibe, proprotein convertase subtilisin/kexin type 9 inhibitors, and bile acid sequestrants are often necessary to further reduce the risk of atherosclerotic cardiovascular disease. This review provides practical guidance as to the use of bempedoic acid to lower LDL-C and includes direction as to which patients may benefit and advice for safety monitoring during treatment. Bempedoic acid, a new class of agent, is a prodrug converted to bempedoyl-CoA by very long-chain acyl-CoA synthetase 1, an enzyme with high expression in the liver but that is undetectable in the skeletal muscle. Bempedoic acid inhibits the enzyme adenosine triphosphate (ATP)-citrate lyase, which lies two steps upstream from β-hydroxy β-methylglutaryl-CoA reductase in the cholesterol biosynthesis pathway. In clinical trials conducted in patients with or at risk for atherosclerotic cardiovascular disease or familial heterozygous hypercholesterolemia, bempedoic acid in combination with statins and/or ezetimibe significantly reduced LDL-C, apolipoprotein B, and high-sensitivity C-reactive protein compared with placebo. Bempedoic acid is generally well tolerated with no clinically meaningful increase in muscle-related symptoms relative to placebo, even in patients taking maximally tolerated statins. A small increase in serum uric acid (mean increase 0.8 mg/dL) is the most noteworthy adverse effect. Bempedoic acid provides an effective and generally well-tolerated medication to further reduce LDL-C in patients taking maximally tolerated statins or manage LDL-C levels in those who are unable to take statins. The potential for a reduced incidence of major cardiovascular events with bempedoic acid is being investigated in the CLEAR Outcomes trial, with results expected in 2023.

Topics: Cholesterol, LDL; Coronary Artery Disease; Dicarboxylic Acids; Drug Tolerance; Fatty Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Hypolipidemic Agents; Treatment Outcome

The lowered LDL-C treatment goal of the 2019 European Society of Cardiology dyslipidemia guidelines results in a significant increase in the projected need for cost-intensive proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. Addition of bempedoic acid (BA) to established oral lipid-lowering medication (LLM) has the potential to enable affordable LDL-C goal attainment, particularly in patients with statin intolerance (SI). The goal of this study was to quantify the target populations for BA and PCSK9 inhibitors as well as the related treatment costs to achieve the LDL-C goal of <55 mg/dL and a ≥50% reduction assuming the addition of BA to LLM.. This study included 1922 patients with coronary artery disease (CAD) from the contemporary observational cohort study INTERCATH. A Monte Carlo simulation incorporating an algorithm adding sequentially a statin, ezetimibe, optionally BA, and a PCSK9 inhibitor was applied to achieve the LDL-C treatment goal, with consideration of both partial and total SI. Two scenarios were simulated for both a moderate (2% full and 10% partial) and a high (12% full) rate of SI: (1) without BA; and (2) with BA.. Patients' mean age was 69.3 years, and the median baseline LDL-C level was 86.0 mg/dL. The need for a PCSK9 inhibitor would be 41.4% for a moderate rate of SI and 46.1% for a high rate of SI. Addition of BA would: (1) reduce the need for a PCSK9 inhibitor to 25.3% and 29.4%, thus lowering the annual overall treatment cost incurred through PCSK9 inhibitor ± BA per 1 million patients with CAD by 13.3% and 10.5%; (2) lower the cost per prevented event in the entire cohort (-5.0% and -6.3%), although at the price of fewer prevented events (-8.7% and -4.5%); and (3) reduce the cost per prevented event (-6.8% for both rates of SI) while preventing more events (7.6% and 6.9%) in the subpopulation of patients with full SI.. Use of BA is projected to reduce the need for PCSK9 inhibitors as well as the treatment cost for add-on LLM. The subpopulation of patients with full SI might profit particularly.

Topics: Aged; Anticholesteremic Agents; Cholesterol, LDL; Cohort Studies; Coronary Artery Disease; Dicarboxylic Acids; Fatty Acids; Health Care Costs; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Proprotein Convertase 9

Topics: Coronary Artery Disease; Cost-Benefit Analysis; Dicarboxylic Acids; Drug Therapy, Combination; Fatty Acids; Humans; Hypercholesterolemia; Hypolipidemic Agents; Models, Economic; RNA, Small Interfering; Secondary Prevention; Treatment Outcome

Bempedoic acid (BemA; ETC-1002) is a novel drug that targets hepatic ATP-citrate lyase to reduce cholesterol biosynthesis. In phase 2 studies, BemA lowers elevated low-density lipoprotein cholesterol (LDL-C) in hypercholesterolemic patients. In the present study, we tested the ability of BemA to decrease plasma cholesterol and LDL-C and attenuate atherosclerosis in a large animal model of familial hypercholesterolemia.. Gene targeting has been used to generate Yucatan miniature pigs heterozygous (. In a large animal model of LDLR deficiency and atherosclerosis, long-term treatment with BemA reduces LDL-C and attenuates the development of aortic and coronary atherosclerosis in both

Topics: Animals; Animals, Genetically Modified; Anticholesteremic Agents; Aortic Diseases; Atherosclerosis; Biomarkers; Cholesterol, LDL; Coronary Artery Disease; Dicarboxylic Acids; Disease Models, Animal; Down-Regulation; Fatty Acids; Female; Gene Expression Regulation; Genetic Predisposition to Disease; Hyperlipoproteinemia Type II; Male; Phenotype; Plaque, Atherosclerotic; Receptors, LDL; Swine; Swine, Miniature