Viet Le, DMSc, MPAS, PA-C, FACC, FAHA

An expert discusses how the CLEAR Outcomes trial data demonstrated that bempedoic acid effectively reduces cardiovascular events by 13% in nearly 14,000 statin-intolerant patients over 4.9 years with excellent tolerability, while long-term data from PCSK9 inhibitor studies such as the FOURIER trial show sustained safety and efficacy over five to eight years with the principle that “lower for longer is better,” as patients who started treatment earlier maintained cardiovascular protection advantages that late-starters could never catch up to despite achieving similar LDL reductions.

An expert discusses how the “lower for longer is better” principle drives current guideline updates, with the National Lipid Association and American Diabetes Association now recommending more aggressive LDL cholesterol targets (less than 70 mg/dL for patients with diabetes) and earlier initiation of combination therapies. The recent 2025 ESC guidelines establish even lower targets, including less than 40 mg/dL for extreme-risk patients and recommend bempedoic acid as monotherapy for statin-intolerant patients or in combination therapy, with oral medications preferred before injectables.

An expert discusses how underutilization of combination lipid-lowering therapies stems from overly complex guidelines, primary care providers managing multiple chronic diseases simultaneously, cost and insurance coverage concerns, unfamiliarity with newer medications, and systemic health care barriers. He notes that these issues are particularly problematic when 50% of patients who experienced a heart attack are not even receiving foundational statin therapy 6 months post event.

An expert discusses how nonstatin therapies serve as essential tools when patients can’t tolerate statins or need additional LDL cholesterol-lowering agents. These include ezetimibe (a cholesterol absorption inhibitor), bempedoic acid (a liver-specific prodrug) and PCSK9-interfering therapies (both injectable monoclonal antibodies and inclisiran), with treatment selection based on patient comorbidities, cardiovascular risk level and specific LDL cholesterol targets.

An expert discusses how primary and secondary prevention differ in atherosclerotic cardiovascular disease, with secondary prevention targeting patients who have already had events such as heart attacks or strokes and primary prevention addressing high-risk patients with multiple risk factors. He explains that statin intolerance can be complete (due to severe complications such as rhabdomyolysis) or partial (ranging from mild to severe muscle aches), while statin resistance occurs when patients tolerate the medication but don’t achieve expected LDL cholesterol reductions.