Alternatives to Repatha (Evolocumab) for Lowering LDL-C

PCSK9 Inhibitor Alternatives

The American College of Cardiology recommends alirocumab as a class-equivalent alternative to evolocumab, reducing LDL-C by 50-65% with a similar safety profile and mechanism of action as another PCSK9 inhibitor, in patients with established cardiovascular disease or primary hyperlipidemia 1
Alirocumab reduces LDL-C by 45-58% when added to maximally tolerated statin therapy, with a comparable efficacy to evolocumab, in patients with high cardiovascular risk 2

Ezetimibe should be considered as the next alternative if PCSK9 inhibitors are unsuitable, offering oral administration and proven cardiovascular benefit, with a mechanism of inhibiting NPC1L1 protein in the small intestine, reducing cholesterol absorption, and reducing LDL-C by approximately 18% as monotherapy and an additional 25% when combined with statins, in patients with primary hyperlipidemia or established cardiovascular disease 2
Bempedoic acid is particularly valuable for statin-intolerant patients as it inhibits ATP citrate lyase, reducing cholesterol synthesis without causing muscle-related side effects, and can be used as monotherapy or as add-on therapy, in patients with statin intolerance or primary hyperlipidemia 2
Mipomersen is an antisense oligonucleotide that binds apolipoprotein B mRNA, reducing LDL-C by approximately 30%, and is particularly useful in homozygous familial hypercholesterolemia (FH) patients as it does not require functional LDL receptors, but has concerns including injection site reactions, influenza-like symptoms, transaminase elevations, and hepatic steatosis, limiting its use to severe cases 3

The American College of Cardiology recommends optimizing statin therapy before adding non-statin agents, with a goal to achieve >50% LDL-C reduction in high-risk patients, and considering alirocumab as the first alternative if another PCSK9 inhibitor is acceptable, followed by ezetimibe, bempedoic acid, and mipomersen for specific patient populations 1, 2
Combination therapy with multiple non-statin agents, such as ezetimibe and bempedoic acid, should be considered for greater efficacy in statin-intolerant patients, rather than relying on monotherapy, as recommended by the American College of Cardiology 2