Bempedoic Acid: Lipid Lowering for Cardiovascular Disease Prevention.

Heart Int

Ciccarone Center for the Prevention of Cardiovascular Disease, Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Published: November 2023

AI Article Synopsis

  • Management of LDL-C levels is crucial for preventing cardiovascular disease, with statins recommended as the first-line treatment.
  • Up to 30% of patients experience statin intolerance, impacting their ability to achieve desired LDL-C levels, prompting interest in alternative therapies.
  • Bempedoic acid, a new non-statin drug, has been shown to significantly reduce cardiovascular events in statin-intolerant patients, providing a promising option for effective LDL-C management.

Article Abstract

The management of low-density lipoprotein cholesterol (LDL-C) levels is a central strategy for the prevention of atherosclerotic cardiovascular disease. Current United States (2018 American Heart Association/American College of Cardiology/Multisociety) and European (2019 European Society of Cardiology/European Atherosclerosis Society) guidelines endorse statin therapy as the first-line therapy for pharmacologic LDL-C lowering. However, in clinical practice up to 30% of patients report partial or complete intolerance to statin therapy. While the nocebo effect with statins is well described, perceived statin intolerance prevents many patients from achieving LDL-C thresholds associated with clinical benefit. Bempedoic acid is a novel, oral, non-statin lipid-l owering therapy that works by inhibiting adenosine triphosphate-citrate lyase, an enzymatic reaction upstream of 3-hydroxy-3-methylglutaryl coenzyme A reductase in the hepatic cholesterol synthesis pathway. Bempedoic acid confers reduction in LDL-C of ~18% on background statin therapy,~21% in patients with statin intolerance, and ~38% when given in fixed-dose combination with ezetimibe. The CLEAR Outcomes trial, which enrolled high-risk primary and secondary prevention patients with reported statin intolerance and LDL-C levels ≥100 mg/dL, showed that bempedoic acid compared with placebo reduced 4-component major adverse cardiovascular events (MACE) by 13% (hazard ratio 0.87, 95% confidence interval 0.79-0.96). Bempedoic acid also reduced 3-component MACE by 15%, myocardial infarction by 23% and coronary revascularization by 19%. The benefit was even greater in the primary prevention cohort (hazard ratio 0.70, 95% confidence interval 0.55-0.89) for 4-component MACE. Bempedoic acid was associated with increases in uric acid levels and cholelithiasis, but numerically fewer events of myalgia and new-onset diabetes. These findings confirm that bempedoic acid is an effective approach to reduce cardiovascular outcomes in high-risk patients with statin intolerance who require further reduction in LDL-C.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10900064PMC
http://dx.doi.org/10.17925/HI.2023.17.2.1DOI Listing

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