New post-hoc analyses from the landmark CLEAR Outcomes trial reveal that bempedoic acid (NEXLETOL) demonstrates significant cardiovascular benefits both as monotherapy and in reducing venous thromboembolism events. The data, presented at the 2025 American Heart Association Scientific Sessions in New Orleans, provides compelling evidence for the drug's efficacy in statin-intolerant patients.
Monotherapy Shows Robust Cardiovascular Protection
In a secondary analysis examining patients receiving no background lipid-lowering therapies, bempedoic acid monotherapy demonstrated a 14% reduction in MACE-4 events (cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, or coronary revascularization) compared to placebo. The analysis included approximately 8,200 patients, representing over half (59%) of the 13,970 participants in the CLEAR Outcomes trial.
"Bempedoic acid is a proven drug to reduce risk for adverse cardiovascular outcomes such as heart attack and stroke in patients who cannot take recommended statin therapy," said Luke Laffin, MD, senior author for the CLEAR Outcomes sub-analyses and Associate Professor of Medicine at the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University.
The monotherapy group also achieved a meaningful 20.6% reduction in LDL cholesterol at six months, demonstrating both lipid-lowering efficacy and clinical outcomes benefit. Safety profiles remained consistent, with total adverse events, serious adverse events, and discontinuation rates similar between bempedoic acid and placebo groups.
Unexpected Benefits in Venous Thromboembolism Prevention
A separate exploratory analysis revealed an unexpected benefit of bempedoic acid in preventing venous thromboembolism events. Over 40.6 months of follow-up, patients treated with bempedoic acid experienced a 42% reduction in any venous thromboembolism event compared to placebo, with 106 total VTE events occurring during the study period.
The protective effect was consistent across VTE subtypes, with deep venous thrombosis risk reduced by 44% and pulmonary embolism risk decreased by 39%. These findings suggest bempedoic acid may provide cardiovascular benefits beyond its established role in preventing atherosclerosis.
"The new data suggests bempedoic acid may have benefits beyond preventing atherosclerosis by preventing deep venous thrombosis and pulmonary embolism," Laffin noted.
Clinical Implications for Statin-Intolerant Patients
The analyses underscore bempedoic acid's potential to address critical unmet needs in preventive cardiology, particularly for patients unable to tolerate statin therapy. Sheldon Koenig, President and CEO of Esperion, emphasized the clinical significance of these findings.
"These new analyses from CLEAR Outcomes continue to reinforce the clinical value of NEXLETOL as a foundational therapy for cardiovascular risk reduction, particularly in patients who are unable to tolerate statins," Koenig stated. "The consistency of benefit seen with bempedoic acid monotherapy - both in lowering LDL-C and reducing major adverse cardiovascular events - underscores its potential to address a critical unmet need in preventive cardiology."
Regulatory Status and Safety Profile
NEXLETOL is currently indicated to reduce the risk of myocardial infarction and coronary revascularization in adults unable to take recommended statin therapy, either with established cardiovascular disease or at high risk for cardiovascular events. The drug is also approved as an adjunct to diet for reducing LDL cholesterol in adults with primary hyperlipidemia.
The most common adverse reactions in cardiovascular outcomes trials occurring at ≥2% incidence and 0.5% greater than placebo included hyperuricemia, renal impairment, anemia, elevated liver enzymes, muscle spasms, gout, and cholelithiasis. Important safety considerations include monitoring for hyperuricemia and potential tendon rupture, particularly in patients over 60 years of age.
