Where Should Inclisiran Sit After Statins and Ezetimibe in ASCVD Care?

When should a patient with ASCVD and LDL-C above goal be referred for injectable lipid therapy?

Refer once the patient has established ASCVD, remains above LDL-C goal despite maximally tolerated oral therapy, and is a plausible candidate for a PCSK9 inhibitor or other injectable lipid-lowering agent. In practice, do not wait indefinitely after statin failure: optimise oral therapy first, then refer if LDL-C is st

How does inclisiran differ from PCSK9 monoclonal antibodies in mechanism and dosing?

Inclisiran and PCSK9 monoclonal antibodies (mAbs) both lower LDL-C by increasing hepatic LDL receptor availability, but they do so at different points in the PCSK9 pathway. Inclisiran is a small interfering RNA (siRNA) taken up by hepatocytes that causes intracellular degradation of PCSK9 mRNA, thereby reducing hepatic

Which ASCVD phenotypes are best suited for inclisiran after maximally tolerated statin and ezetimibe?

After maximally tolerated statin + ezetimibe, inclisiran is best suited to very-high-risk ASCVD patients who remain above LDL-C goal, especially those with recurrent/polyvascular disease, recent ACS, familial hypercholesterolemia phenotype, or patients in whom long-term adherence to frequent self-injection is a barrier

How should we choose between inclisiran and a PCSK9 monoclonal antibody when adherence and outcomes evidence point differently?

If the main priority is maximising proven cardiovascular event reduction today, a PCSK9 monoclonal antibody is generally preferred, because evolocumab and alirocumab have completed large outcomes trials showing reduction in major adverse cardiovascular events, whereas inclisiran has robust LDL-C lowering data but defin

What monitoring schedule and LDL-C response threshold best identify an inadequate response to inclisiran?

For inclisiran, the most practical way to detect an inadequate LDL-C response is to check baseline LDL-C, then repeat fasting or non-fasting lipid profile at about 3 months after the first dose (i.e., near the time of the second dose or soon after steady early effect is evident), and again before subsequent maintenance