Is It CLEAR? Bempedoic Acid vs. Statins

November 15, 2024

Written by Babatunde Carew

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Bempedoic acid, when given to statin-intolerant patients, showed comparable outcomes to statins for overall risk reduction but fell short in fatal coronary events and fatal or nonfatal stroke. 

Synopsis
The CLEAR Outcomes trial found that bempedoic acid, when administered to statin-intolerant patients, reduced LDL cholesterol levels by 21% and resulted in a 13% relative reduction in major adverse cardiovascular events (MACE). This secondary analysis applied Cholesterol Treatment Trialists’ Collaboration (CTTC) methods. When adjusted for a 1 mmol/L reduction in low-density lipoprotein cholesterol (LDL-C), bempedoic acid showed a hazard ratio (HR) of 0.75 (95%CI 0.63-0.90) for major vascular events, which is comparable to the HR of 0.78 seen in statin trials. The study found similar reductions in key outcomes like nonfatal myocardial infarction (HR 0.73) and coronary revascularization (HR 0.81), suggesting that bempedoic acid offers cardiovascular protection similar to statins when adjusted for magnitude of LDL-C reduction. [AI-generated, physician edited]

Maybe not so CLEAR 
Statin associated muscle symptoms occur in 10-25% of patients, limiting adherence to statin therapy, as the only effective treatment is cessation of statin therapy. In a high risk, statin-intolerant population, bempedoic acid shows promise as an alternative, as it targets cholesterol synthesis upstream from HMG-CoA reductase. This was a pre-specified secondary analysis of the CLEAR Outcomes trial, comparing CTTC analysis risk reduction by bempedoic acid to statin therapy. For each 1mmol/L LDL-C reduction, bempedoic acid was comparable to statin therapy in major vascular events, major coronary events, non-fatal MI, and coronary revascularization but fell short in fatal coronary heart disease and fatal or nonfatal stroke. While bempedoic acid shows promise as an add-on to meet LDL goals or as monotherapy for statin-intolerant patients, the superior risk reduction and cost-effectiveness of statins should have us trialing different statin drugs before switching to bempedoic acid. With more drug classes (PCSK9 inhibitor, CETP inhibitors, AGLP3, and combination drugs) being added to reduce LDL, we need to monitor this space for indications for each. 

Source 
Comparative Cardiovascular Benefits of Bempedoic Acid and Statin Drugs. J Am Coll Cardiol. 2024 Jul 9;84(2):152-162. doi: 10.1016/j.jacc.2024.04.048. PMID: 38960508