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Factors Associated With Enhanced Low-Density Lipoprotein Cholesterol Lowering With Bempedoic Acid.

ABSTRACT: Background Bempedoic acid (BA) inhibits ATP-citrate lyase in the cholesterol synthesis pathway and lowers low-density lipoprotein cholesterol (LDL-C). As with other lipid-lowering therapies, interindividual variation in response to BA was observed in clinical trials. We characterized LDL-C response to BA using guideline-defined statin intensity categories and identified clinical factors associated with enhanced LDL-C lowering with BA. Methods and Results This post hoc analysis used pooled data from 4 phase 3 studies. Patients were randomized 2:1 to once-daily BA 180 mg (n=2321) or placebo (n=1167) for 12 to 52 weeks and grouped based on percent change in LDL-C from baseline to week 12 according to guideline-established statin intensity categories. Factors associated with ≥30% reduction in LDL-C were identified using logistic regression analyses. From baseline to week 12, BA lowered LDL-C levels comparable to a moderate- or high-intensity statin (≥30%) in 28.9% of patients; this degree of LDL-C lowering was observed in 50.9% of patients not receiving background statin therapy. In a multivariable analysis, the absence of statins, female sex, a history of diabetes, ezetimibe use, and higher high-sensitivity C-reactive protein level were associated with increased rates of achieving ≥30% LDL-C reduction with BA (P<0.01 for each). Conclusions A large percentage of patients receiving BA achieved LDL-C reductions comparable to a moderate- or high-intensity statin. Factors including statin absence, female sex, diabetes history, ezetimibe use, and a higher high-sensitivity C-reactive protein level may be useful to identify patients who may have a greater LDL-C reduction with BA. Registration URL: https://www.clinicaltrials.gov; Unique identifiers: NCT02666664, NCT02991118, NCT02988115, NCT03001076.

SUBMITTER: Ballantyne CM

PROVIDER: S-EPMC9375471 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Factors Associated With Enhanced Low-Density Lipoprotein Cholesterol Lowering With Bempedoic Acid.

Ballantyne Christie M CM Bays Harold E HE Louie Michael J MJ Smart Jeremy J Zhang Yang Y Ray Kausik K KK Ray Kausik K KK

Journal of the American Heart Association 20220802 15

Background Bempedoic acid (BA) inhibits ATP-citrate lyase in the cholesterol synthesis pathway and lowers low-density lipoprotein cholesterol (LDL-C). As with other lipid-lowering therapies, interindividual variation in response to BA was observed in clinical trials. We characterized LDL-C response to BA using guideline-defined statin intensity categories and identified clinical factors associated with enhanced LDL-C lowering with BA. Methods and Results This post hoc analysis used pooled data f ...[more]

PMID: 35916348

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Project description:Purpose of reviewThe primary and secondary prevention of atherosclerotic cardiovascular disease (ASCVD) relies on optimizing cardiovascular health and appropriate pharmacotherapy, a mainstay of which is low-density lipoprotein-cholesterol (LDL-C) lowering. Typically, statin therapy remains the first line approach. Advances in technology and understanding of lipid metabolism have facilitated the development of several novel therapeutic targets and medications within the last decade. This review focuses on medications recently approved by the U.S. Food and Drug Administration (FDA) for the reduction of LDL-C and ASCVD risk, as well as new therapies in the pipeline.Recent findingsNovel lipid therapies aim to lower risk of ASCVD by targeting reduction of atherogenic compounds, such as LDL, lipoprotein(a) (Lp(a)), and triglyceride-rich lipoproteins. Evolocumab and alirocumab, monoclonal antibody proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors which lower LDL-C by approximately 60%, have emerged as important therapies for use in patients with ASCVD as well as familial hypercholesterolemia (FH). Bempedoic acid, an ATP citrate lyase inhibitor, is an oral medication recently approved that can lower LDL-C by approximately 18% alone and 38% when combined with ezetimibe. Inclisiran, a small-interfering RNA (siRNA) molecule which inhibits the translation of PCSK9, is the most recently FDA-approved LDL-C lowering medication, and can reduce LDL-C by approximately 50% with twice yearly subcutaneous dosing. The cardiovascular outcome trials for bempedoic acid and inclisiran are still on-going. Evinacumab, a monoclonal antibody which targets angiopoietin-like protein 3 (ANGPTL3), has been approved for use in patients with homozygous FH. SiRNAs and anti-sense oligonucleotides (ASO) facilitating selective inhibition of the production of targeted proteins including Lp(a) and ANGLPTL3 are active areas of clinical investigation.SummaryRecently several novel LDL-C lowering medications have been approved. New therapeutic targets have been identified and present additional means of lowering LDL-C and other atherogenic compounds for patients who remain at high ASCVD risk.

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Factors Associated With Enhanced Low-Density Lipoprotein Cholesterol Lowering With Bempedoic Acid.

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Factors Associated With Enhanced Low-Density Lipoprotein Cholesterol Lowering With Bempedoic Acid.

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