Bempedoic Acid: Lipid Lowering for Cardiovascular Disease Prevention

Area of Science:

• Cardiology
• Pharmacology
• Metabolic Diseases

Background:

• Atherosclerotic cardiovascular disease (ASCVD) management relies on lowering low-density lipoprotein cholesterol (LDL-C).
• Statins are first-line therapy, but up to 30% of patients experience intolerance, hindering LDL-C goal achievement.
• Perceived statin intolerance, including the nocebo effect, poses a significant clinical challenge.

Purpose of the Study:

• To evaluate bempedoic acid, a novel non-statin lipid-lowering agent, in patients with statin intolerance.
• To assess the efficacy and safety of bempedoic acid in reducing LDL-C and major adverse cardiovascular events (MACE).

Main Methods:

• The CLEAR Outcomes trial enrolled high-risk patients with statin intolerance and elevated LDL-C (≥100 mg/dL).
• Bempedoic acid's effect on LDL-C reduction was assessed alone and in combination with ezetimibe.
• Cardiovascular outcomes, including 4-component MACE, were compared between bempedoic acid and placebo.

Main Results:

• Bempedoic acid achieved ~18% LDL-C reduction with statins, ~21% in statin-intolerant patients, and ~38% with ezetimibe.
• The trial demonstrated a 13% reduction in 4-component MACE (HR 0.87) with bempedoic acid versus placebo.
• Significant reductions were observed in myocardial infarction (23%) and coronary revascularization (19%), with greater benefit in primary prevention.

Conclusions:

• Bempedoic acid is an effective non-statin therapy for reducing LDL-C and cardiovascular outcomes in high-risk patients with statin intolerance.
• The drug offers a valuable alternative for patients requiring further LDL-C lowering beyond statin therapy.
• While associated with increased uric acid and cholelithiasis, bempedoic acid showed numerically fewer myalgia and new-onset diabetes events.