Treatment of Hypercholesterolemia with Bempedoic Acid and Repatha

Introduction to Treatment Hierarchy

The American College of Cardiology recommends adding ezetimibe first, then Repatha (evolocumab) second, and reserving bempedoic acid as third-line therapy for patients requiring additional LDL-cholesterol lowering beyond statins, except in statin-intolerant patients where bempedoic acid moves up in the treatment hierarchy 1, 2

Add ezetimibe 10 mg daily as the initial non-statin agent when maximally tolerated statin therapy fails to achieve target LDL-C levels, providing approximately 18% additional LDL-C reduction as monotherapy and 25% when combined with statins, with proven cardiovascular outcomes benefit in the IMPROVE-IT trial 1, 2
Ezetimibe has demonstrated safety, tolerability, generic availability, and cardiovascular death/MI reduction when added to moderate-intensity statins in acute coronary syndrome patients 2
Add Repatha (evolocumab) 140 mg subcutaneously every 2 weeks or 420 mg monthly if LDL-C remains ≥70 mg/dL or <50% reduction despite statin plus ezetimibe, reducing LDL-C by 40-65% when added to statin therapy and having proven cardiovascular outcomes benefit in the FOURIER trial 1, 2, 3, 4
The American College of Cardiology prioritizes PCSK9 monoclonal antibodies (evolocumab, alirocumab) over other PCSK9 inhibitors due to established cardiovascular outcomes data 4
Consider adding bempedoic acid 180 mg daily if LDL-C remains elevated despite statin, ezetimibe, and Repatha, or if the patient cannot tolerate these therapies, reducing LDL-C by approximately 23% as monotherapy and 15-17.8% when added to statin therapy 1, 3, 5

In patients truly intolerant to statins, bempedoic acid moves to first-line therapy, followed by ezetimibe, then Repatha, with bempedoic acid being activated only in the liver and avoiding statin-associated muscle symptoms 1, 5
Bempedoic acid demonstrated efficacy in statin-intolerant populations in the CLEAR Outcomes trial, with 70% of participants having established ASCVD and 30% being at high risk 5

For patients with ASCVD and baseline LDL-C ≥190 mg/dL requiring rapid, aggressive LDL-C reduction, consider simultaneous addition of ezetimibe plus Repatha to maximally tolerated statin 3
The fixed-dose combination of bempedoic acid 180 mg plus ezetimibe 10 mg provides 38% additional LDL-C reduction when added to statin therapy 1, 6

Monitor serum uric acid levels as bempedoic acid increases uric acid by a mean of 0.8 mg/dL, with gout occurring in 1.5% versus 0.4% with placebo 1
Counsel patients about tendon rupture risk (0.5% versus 0% with placebo), particularly in those with prior tendon disorders 1
Monitor for benign prostatic hyperplasia (1.3% vs 0.1%), atrial fibrillation (1.7% vs 1.1%), and creatine kinase elevation (1.0% vs 0.6%) 1

Bempedoic acid is commercially available as a branded product, with prior authorization required in most insurance plans, but patient assistance programs and discount copay cards are available for eligible patients 1
Repatha similarly requires prior authorization in most insurance plans, with patient assistance programs available 3
The availability of fixed-dose combination bempedoic acid/ezetimibe may improve adherence in patients requiring multiple agents 1, 6