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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http://dx.doi.org/10.17925/HI.2023.17.2.1 | DOI Listing |
Eur Heart J Cardiovasc Pharmacother
December 2024
Vorarlberg Institute for Vascular Investigation and Treatment (VIVIT), Vorarlberg, Austria.
Objectives: This review aims to examine the evidence on the benefits and risks of lipid lowering drugs in patients with liver disease. Elevated liver enzyme levels often lead to cautious discontinuation of these drugs, potentially withholding from patients their benefit in reducing cardiovascular disease morbidity and mortality.
Methods And Results: Using a literature search of PubMed, we examine the efficacy and safety profiles of various lipid lowering agents, including statins, ezetimibe, bempedoic acid, PCSK9 inhibitors, fibrates, and icosapent ethyl, focusing particularly on their potential side effects related to liver health.
Expert Opin Pharmacother
December 2024
Department of Metabolic Medicine/Chemical Pathology Guy's, St Thomas' Hospitals, London, UK.
Introduction: Lipid-lowering therapies are well established for the treatment of cardiovascular disease (CVD). Historically monotherapy studies have been performed, but the introduction of statins has led to these drugs being recognized as baseline therapies and to the investigation of combination therapy of both older and newer medications with them.
Areas Covered: Surrogate marker studies have shown additive effects on LDL-C, triglycerides and HDL-C of combination therapies with statins and these have extended to lipoprotein (a).
Hosp Pharm
December 2024
Department of Pharmacy Practice, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Mysore, India.
Lipid-lowering therapy (LLT) includes a diverse group of pharmaceuticals designed to reduce blood levels of cholesterol and triglyceride (TG), helping to prevent cardiovascular diseases like myocardial infarction and stroke. LLT includes treatment with several lipid-lowering drugs (LLD), including hydroxymethylglutaryl (HMG-CoA) reductase inhibitors (statin), PCSK9 Inhibitors, cholesterol-absorbing inhibitors (Ezetimibe), Bile Acid Sequestrants, Fibrates, Niacin (Vitamin B3), Omega-3 Fatty Acids, Bempedoic Acid, and combination therapy. The efficacy and safety of these molecules vary widely.
View Article and Find Full Text PDFJACC Case Rep
December 2024
Cardiology Unit, Policlinico di Modena Hospital, Modena, Italy.
Myotonic dystrophy type 1 (MD1) is the most common form of muscular dystrophy in adults. MD1 is caused by the expansion of CTG repeats in the DMPK gene and affects various organs beyond muscles. We present a case of a patient with MD1 exhibiting features of metabolic syndrome (MetS), including insulin resistance and dyslipidemia.
View Article and Find Full Text PDFJ Clin Med
December 2024
Interventional Cardiology, Sandro Pertini Hospital, 00157 Rome, Italy.
Cardio-cerebral vascular diseases due to atherosclerosis are still the leading cause of death worldwide. Low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B have been identified as the primary factors responsible for the atherosclerotic process, with a causal effect. Many drugs aimed at reducing LDL-C levels are already on the market, acting in different ways in terms of mechanism of action, efficacy, and safety.
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