Bempedoic acid: new blood (cholesterol-lowering medication)

There is new blood among cholesterol-lowering medications. Bempedoic acid (Nilemdo), a novel, nonstatin lipid-lowering therapy, was approved by Health Canada in late 2025. Bempedoic acid is a first-in-class adenosine triphosphate citrate lyase (ACL) inhibitor.1 It inhibits hepatic biosynthesis of cholesterol that is upstream of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase (the primary target of statins). Bempedoic acid is a prodrug that is activated in the liver, so it is inactive in muscle tissue and appears to carry a lower risk of myopathy versus statins. It reduces low-density lipoprotein cholesterol (LDL-C) by about 17%–28%.2-5Indications and dosingBempedoic acid is indicated to lower LDL-C, as an adjunct to diet, in adults (≥ 18 years of age) with dyslipidemia in combination with statin therapy, with or without ezetimibe or a proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitor (e.g., alirocumab, evolocumab).6 It is also indicated as monotherapy in patients who are intolerant of statin therapy (with or without ezetimibe or a PCSK9 inhibitor). In addition to lowering LDL-C, bempedoic acid is indicated to reduce the risk of major adverse cardiovascular events (MACE) (e.g., cardiovascular death, myocardial infarction [MI], stroke, coronary revascularization) in patients with, or at risk of, atherosclerotic cardiovascular disease (ASCVD) as an add-on to statin therapy (if tolerated) or monotherapy, with or without nonstatin therapy.6There is only one dose: 180 mg orally once daily.6 Although no dosage adjustment is required for patients with chronic kidney disease (CKD), patients with severe renal impairment or end-stage renal disease (estimated glomerular filtration rate < 30 mL/min/1.73 m2) were excluded from clinical trials. No dosage adjustment is required in mild-to-moderate hepatic dysfunction, but it has not been studied in patients with more advanced liver disease (Child-Pugh class C). Like statins, bempedoic acid is contraindicated in patients who are pregnant or breastfeeding.6Cardiovascular outcome dataOnly one large-scale cardiovascular outcome trial with bempedoic acid has been published to date. The CLEAR Outcomes trial enrolled 13,970 patients with established ASCVD (70%) or who were at high risk of ASCVD (30%).7 All patients were either unable or unwilling to take a statin, although very-low-dose statin therapy was permitted (e.g., atorvastatin < 10 mg daily, rosuvastatin < 5 mg daily). Patients were randomized in a double-blind fashion to either bempedoic acid 180 mg daily or matching placebo. Mean age of participants was 66 years, 48% were women and 91% were White. Common comorbidities included hypertension (85%), diabetes (46%) and CKD (21%). At baseline, 23% of patients were taking a very low dose of statin and 12% were taking ezetimibe. Mean baseline LDL-C was 3.6 mmol/L.Median followup was 3.4 years. Mean percent reduction in LDL-C with bempedoic acid, as compared to placebo, was 21% at six months. The primary outcome, a four-point composite of MACE, was lower with bempedoic acid (11.7% versus 13.3%, hazard ratio 0.87, 95% confidence interval 0.79–0.96) for a number needed to treat (NNT) of 63. This was primarily driven by a lower risk of coronary revascularization (NNT of 72) and nonfatal MI (NNT of 91). No significant difference was seen in cardiovascular or all-cause death. The rate of serious adverse events and adverse events leading to study drug discontinuation was similar between the bempedoic acid and placebo groups, as was the risk of myalgias.SafetyBempedoic acid has a relatively low risk of adverse effects. The most common adverse events observed in clinical trials were hyperuricemia (about 4%), painful extremities (about 3%), anemia (about 2.5%), gout (about 1%) and increased liver enzymes (about 1%).6 Of note, painful extremities may just be another way of describing musculoskeletal pain, but it was adjudicated separately from myalgias in the clinical trials. The increase in serum uric acid levels, which may precipitate a gout attack, usually occurs in the first four weeks of therapy. It is recommended to measure a patient’s uric acid level at baseline, but the need for routine monitoring is questionable. Some patients may experience a minor elevation in liver enzymes (alanine aminotransferase and aspartate aminotransferase).6 However, patients are typically asymptomatic and levels tend to normalize with continued therapy. Therefore, it is likely unnecessary to routinely measure liver enzymes. Hypersensitivity reactions, including angioedema, wheezing, urticaria and rash, have been reported via postmarketing surveillance.6Drug interactionsBempedoic acid may increase the plasma concentration of statins, which may in turn cause myopathy. However, no dose adjustments are recommended with statin therapy except when used in combination with simvastatin (maximum dose of 20 mg daily) or pravastatin (maximum dose of 40 mg daily).8 There are no relevant drug–food interactions.6Role in practiceBempedoic acid should primarily be reserved for patients with ASCVD who are intolerant to statin therapy and are either unable to access or unwilling to administer a PCSK9 inhibitor. Of note, bempedoic acid did not increase the risk of myopathy in these patients. Although there are no head-to-head trials of bempedoic acid and a PCSK9 inhibitor, PCSK9 inhibitors are much more potent at lowering LDL-C. Bempedoic acid can be used with or without ezetimibe; however, the majority of patients in the CLEAR Outcomes trial received bempedoic acid monotherapy. Although bempedoic acid is indicated as add-on therapy for patients on a statin, there are no cardiovascular outcome data in this population, and the combination may increase the risk of statin-associated myopathy. The cost of bempedoic acid is approximately $140–$150 per month (more than ezetimibe, but less than a PCKS9 inhibitor), which may still be a barrier for some patients.Arden Barry is a clinical pharmacy and research specialist in ambulatory cardiology at the Jim Pattison Outpatient Care and Surgery Centre in Surrey, BC, and associate professor (partner) at the Faculty of Pharmaceutical Sciences, University of British Columbia in Vancouver, B.C.References:Kelly MS, Sulaica EM, Beavers CJ. Role of bempedoic acid in dyslipidemia management. J Cardiovasc Pharmacol 2020;76:376-88.Ballantyne CM, Banach M, Mancini GBJ, et al. Efficacy and safety of bempedoic acid added to ezetimibe in statin-intolerant patients with hypercholesterolemia: a randomized, placebo-controlled study. Atherosclerosis 2018;277:195-203.Laufs U, Banach M, Mancini GBJ, et al. Efficacy and safety of bempedoic acid in patients with hypercholesterolemia and statin intolerance. J Am Heart Assoc 2019;8:e011662.Ray KK, Bays HE, Catapano AL, et al. Safety and efficacy of bempedoic acid to reduce LDL cholesterol. N Engl J Med 2019;380:1022-32.Goldberg AC, Leiter LA, Stroes ESG, et al. Effect of bempedoic acid vs placebo added to maximally tolerated statins on low-density lipoprotein cholesterol in patients at high risk for cardiovascular disease: the CLEAR Wisdom randomized clinical trial. JAMA 2019;322:1780-8.HLS Therapeutics Inc. Nilemdo (bempedoic acid tablets) product monograph. Etobicoke, ON; November 14, 2025. (accessed March 26, 2026).Nissen SE, Lincoff AM, Brennan D, et al. Bempedoic acid and cardiovascular outcomes in statin-intolerant patients. N Engl J Med 2023;388:1353-64.Bempedoic acid. In: UpToDate Lexidrug. Waltham, MA: UpToDate Inc; April 10, 2026. [subscription required] (accessed April 10, 2026).