Inclisiran Therapy for Atherosclerotic Cardiovascular Disease

Patient Selection and Indications

The American Diabetes Association and American College of Cardiology recommend adding non-statin therapies like inclisiran when LDL-C remains ≥70 mg/dL despite maximally tolerated statin plus ezetimibe therapy in patients with established atherosclerotic cardiovascular disease (ASCVD) 1, 2
For patients with established ASCVD, current guidelines recommend achieving LDL-C <55 mg/dL with ≥50% reduction from baseline, as suggested by the American College of Cardiology and the American Diabetes Association 1, 3

Inclisiran reduces LDL-C by approximately 50% when added to statin therapy, with sustained efficacy over 18 months, as demonstrated in phase 3 trials (ORION-10 and ORION-11) 4
The ORION-3 extension study showed LDL-C reductions of 44.2% maintained through 4 years of treatment, indicating long-term efficacy 4
Inclisiran has demonstrated a favorable safety profile similar to placebo across all clinical trials, with the most common adverse event being mild injection-site reactions 4

The 2024 International Lipid Expert Panel guidelines endorse inclisiran for patients with ASCVD who fail to reach LDL-C goals on statin therapy, as reported in the journal Drugs 4
The 2025 American Diabetes Association Standards of Care list inclisiran as a PCSK9 inhibitor option for secondary prevention in ASCVD, as stated in the journal Diabetes Care 1
The American College of Cardiology supports inclisiran as an adjunct to maximally tolerated statin therapy for patients with clinical ASCVD requiring additional LDL-C lowering, according to the Praxis Medical Insights: Practical Summaries of Clinical Guidelines 3

The maintenance dosing of inclisiran every 6 months offers significant adherence advantages over daily oral medications or monthly injectable PCSK9 inhibitors, as suggested by the Praxis Medical Insights: Practical Summaries of Clinical Guidelines 5, 2
Inclisiran should be continued long-term as maintenance therapy for patients with established ASCVD, given the chronic nature of their cardiovascular disease and the need for sustained LDL-C reduction, as recommended by the Praxis Medical Insights: Practical Summaries of Clinical Guidelines 5

The American College of Cardiology recommends that if LDL-C remains ≥100 mg/dL (or non-HDL-C ≥130 mg/dL) despite inclisiran therapy, referral to a lipid specialist is recommended 6
In the VICTORION-Initiate study, 81.8% of patients achieved LDL-C <70 mg/dL with inclisiran versus 22.2% with usual care, and 71.6% achieved <55 mg/dL versus 8.9% with usual care, demonstrating the efficacy of inclisiran therapy 7

The safety profile of inclisiran is favorable and similar to placebo, with serious adverse events occurring at comparable rates, as reported in the Drugs journal 7