How to Select Between Available LDL-C Lowering Therapies

Summary

The experts discuss considerations around selecting non-statin therapies for high cholesterol, either as add-on options to maximally tolerated statins or alternatives for statin-intolerant patients. The choice depends on the degree of additional LDL lowering required to reach one's personalized LDL "end zone" or target.

If the LDL is not too far from goal, options like ezetimibe, which reduces LDL around 20%, may suffice. The new agent bempedoic acid lowers LDL 17-24% and has demonstrated cardiovascular event reduction in a large outcomes trial in statin-intolerant patients. For larger LDL reductions around 50-60%, injectable PCSK9 inhibitor immunotherapy like evolocumab and alirocumab may be utilized. The recently approved siRNA inclisiran, while highly effective at lowering LDL, lacks outcomes data thus far.

Contraindications are minimal with these newer agents apart from hypersensitivity reactions. However, small creatinine elevations are expected with bempedoic acid due to mild renal effects, while inclisiran and the PCSK9 monoclonal antibodies are not affected by kidney or liver dysfunction given their targeted mechanisms.

In summary, newer non-statin agents provide varying degrees of additive LDL lowering, allowing clinicians to appropriately intensify therapy depending on just how far a patient's LDL level stands from their recommended treatment target. Ongoing assessment of changing cardiovascular risk helps determine the appropriate LDL "end zone" to guide medication selection.

This summary was AI-generated and edited for clarity and readability.