Management of Hyperlipidemia with Leqvio (Inclisiran)

Patient Risk Assessment

The American College of Cardiology recommends that patients with minimal evidence of atherosclerotic cardiovascular disease (ASCVD) and an LDL-C level of 90 mg/dL do not meet the threshold for established clinical ASCVD requiring additional non-statin therapy 1, 2
The American College of Cardiology guidelines state that an LDL-C level of 90 mg/dL does not meet the guideline thresholds for adding PCSK9 inhibitors in patients without established ASCVD 3, 4
Risk-enhancing factors such as elevated Lp(a), coronary artery calcium score, and family history of coronary artery disease alone do not justify inclisiran without established ASCVD 2, 5

The American College of Cardiology recommends that PCSK9 inhibitors like inclisiran should be reserved for patients with established ASCVD who have LDL-C ≥70 mg/dL despite maximally tolerated statin therapy plus ezetimibe 4, 6
For patients without established ASCVD but with severe primary hypercholesterolemia (LDL-C ≥190 mg/dL), addition of inclisiran would only be considered if LDL-C remains ≥100 mg/dL despite statin plus ezetimibe therapy 3, 5

The American Heart Association and American College of Cardiology recommend adding ezetimibe as the first non-statin agent before considering PCSK9 inhibitors when LDL-C remains above target on maximally tolerated statin therapy 1, 2
Ezetimibe provides an additional 15-25% LDL-C reduction when added to statin therapy and has a better safety profile and lower cost compared to PCSK9 inhibitors 8

Inclisiran has demonstrated LDL-C lowering of approximately 50% in clinical trials, but its effect on cardiovascular outcomes has not yet been determined 4
The most common adverse effects of inclisiran are injection site reactions, which occurred in 5.0% of patients versus 0.7% with placebo in clinical trials 4

Inclisiran represents a significant cost burden compared to ezetimibe, which is available as a generic medication 8
The American College of Cardiology guidelines note that cost-effectiveness of PCSK9 inhibitors was low at mid-2018 list prices, and while costs have decreased, they remain substantial 2, 3