LDL-C Optimization Using Inclisiran in Patients in Which Drug-Drug Interactions Limit LDL Lowering

This is an investigator-initiated, single-site, open-label, randomized trial. The investigators will enroll up to 100 high-risk primary prevention patients with at least one comorbidity and an indication for additional lipid control (such as Type II diabetes with A1c ≤ 8.5%, subclinical atherosclerosis, or increased 10-year ASCVD risk). Patients will be randomized 1:1 to the inclisiran arm (n ≥ 50) with standard of care or standard of care alone (n ≥ 50). The study will consist of five study visits (screening, baseline, 3 months, 9 months, and 12 months). Patients in the inclisiran arm will receive a subcutaneous injection of inclisiran 284 mg for three doses (baseline, 3 months, and 9 months following randomization) as add-on therapy. LDL-C (the primary endpoint) along with other biomarkers will be measured at screening, baseline (inclisiran dose #1), 3 months (inclisiran dose #2), 9 months (inclisiran dose #3), and 12 months (labs only). Patients will also undergo medical history and medication review at each visit. Surveys will be completed at each visit during the study period. Patients in the control arm (standard of care) will continue with their current lipid-lowering therapy. No adjustments will be made to lipid-lowering therapy during the course of the study. Participants will be aware of the group to which they have been randomized. The primary objective is to determine the efficacy of inclisiran for LDL-C lowering in high-risk primary prevention patients with multiple comorbidities (e.g., type II diabetes, autoimmune disease, liver disease, chronic kidney disease, solid-organ transplant) who are taking five or more medications in which drug-drug interactions may prevent optimization of statin therapy.