Bempedoic Acid in Statin-Intolerant Patients: Real-World Implementation Strategies, Cardiovascular Outcomes Beyond the CLEAR Trial, and Combination Therapy Approaches

Purpose of the Review Statin intolerance remains a significant barrier to achieving lipid goals and reducing atherosclerotic cardiovascular disease (ASCVD) risk. Bempedoic acid (BA), an oral ATP-citrate lyase inhibitor activated predominantly in the liver, offers a non-statin lipid-lowering option with a low propensity for muscle-related adverse effects. This review seeks to discuss BA use in real-world practice. Recent Findings This review summarizes BA pharmacology, cardiovascular outcomes, safety, combination strategies, and real-world implementation in individuals who are either statin intolerant or unwilling to take statins. The CLEAR clinical trial series established BA's lipid-lowering effect and safety profile, culminating in CLEAR Outcomes, which further demonstrated fewer major adverse cardiovascular events among patients with established ASCVD or at high cardiovascular risk. Although these findings are compelling, they are limited to this population, and the impact in low- to borderline-risk populations remains unclear. Summary In practice, clinicians should assess the potential contribution of the nocebo effect, distinguish partial versus complete statin intolerance, preserve any tolerated statin exposure, define the residual lipid-lowering gap, and align treatment intensity with cardiovascular risk and patient preferences. BA may then be considered within a guideline-directed framework that accounts for treatment access, tolerability, and shared decision-making. Combination therapy with BA and ezetimibe represents a practical oral option, whereas PCSK9-targeted therapy may be preferred when the gap to lipid goals is sufficiently large or the patient is at high ASCVD risk. Clinicians should also provide risk-based counseling and monitoring for potential adverse effects, including hyperuricemia, gout, and tendon injury. Overall, BA represents a valuable addition to the lipid-lowering armamentarium.