Bempedoic Acid: Results of the CLEAR Program

Bempedoic acid is a fairly small molecule acting as a prodrug which is converted into the active compound bempedoyl-CoA in the liver.This active metabolite of bempedoic acid inhibits the enzyme ATP citrate lyase leading to low-density lipoprotein (LDL) reduction.The CLEAR (Cholesterol Lowering via Bempedoic Acid, an ACL-Inhibiting Regimen) Harmony trial showed that bempedoic acid reduced LDL cholesterol (LDL-C) by 12.6-16.5% and the CLEAR Tranquility and Serenity showed a reduction of LDL-C in statin-intolerant patients by a mean of 21% in monotherapy and 38% in combination with ezetimibe.Similar to statins but in contrast to ezetimibe or PCSK9 inhibitors, there was a consistent reduction of high-sensitive C-reactive protein in patients treated with bempedoic acid throughout all those studies.The CLEAR Outcomes trial included patients with established atherosclerotic cardiovascular disease (ASCVD) or a high risk of developing it, a documented intolerance to statin and a LDL ≥2.6 mmol/l despite maximal tolerated lipid-lowering therapy.The study showed that bempedoic acid lowered LDL by 21% and reduced the risk of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke or coronary revascularization (primary composite endpoint) over a median of 3.4 years in statin-intolerant patients.The safety profile showed a slight increase in uric acid, gout and cholelithiasis.Bempedoic acid, used alone or with ezetimibe, is an effective LDL-lowering therapy for patients who do not attain adequate LDL-C control with maximal tolerated statin therapy and in statin-intolerant patients at risk for ASCVD.