Bempedoic Acid: Safety and Efficiacy of a New Lipid-Lowering Agent

Scientific relevance. Lowering low-density lipoprotein cholesterol (LDL-C) levels with statins is a generally accepted standard treatment for dyslipidaemia. However, adverse reactions and intolerance to statins have motivated the search for lipid-modifying agents with alternative mechanisms of action. Bempedoic acid is one of these alternative agents. Aim. The study aimed to review published data on the mechanism of action, pharmacokinetics, pharmacodynamics, safety and efficacy of bempedoic acid used as a lipid-lowering agent. Discussion. Similar to statins, bempedoic acid inhibits cholesterol synthesis from acetyl-CoA. Statins and bempedoic acid differ in their mechanisms of action mainly because the conversion of bempedoic acid into its active metabolite takes place only in the liver. As a result, bempedoic acid does not cause adverse drug reactions in muscles. The main safety and efficacy data on bempedoic acid were obtained in phase III CLEAR trials. Compared to placebo, bempedoic acid reduced LDL-C levels by an additional 18% in combination with maximum tolerated doses of statins and by 25% in monotherapy in patients with statin intolerance. In the CLEAR Outcomes trial, long-term treatment with bempedoic acid reduced the risk of major adverse cardiovascular events in patients with statin intolerance (n=13970) by 13%. A slight increase in gout attack frequency was observed, primarily in patients with pre-existing hyperuricaemia. Conclusions. Therefore, bempedoic acid is a safe and effective treatment option for patients with dyslipidaemia at high risk of atherosclerotic cardiovascular disease. It can be used either in combination with statins or, in the case of statin intolerance, as monotherapy and with ezetimibe.