Drug-drug interactions often limit statin optimization in a population of patients prescribed cytochrome P3A4 inhibitors, which include immunosuppressive agents, protease inhibitors, and antifungals. These patients frequently have autoimmune conditions or rheumatologic disorders that require complex drug regimens and are often on low-dose statin therapy or no statin at all, resulting in suboptimal LDL levels despite increased cardiovascular (CV) risk.
There is an unmet clinical need to improve LDL levels in this vulnerable patient population, which faces increased CV risk due to underlying conditions that also contribute to polypharmacy and multiple drug-drug interactions. This study is a randomized, open-label trial evaluating subcutaneous inclisiran plus standard of care for LDL-C lowering in high-risk primary prevention patients with multiple comorbidities (e.g., Type II diabetes, liver disease, chronic kidney disease, autoimmune disease, solid-organ transplant) who are taking five or more medications in which drug-drug interactions prevent optimization of statin therapy.
Study of Optimal LDL-C Value Enhancement With Inclisiran in Patients With Multiple Comorbidities in Which There Are Drug-Drug Interactions Limiting LDL-C 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 ASCVD risk of 7.5% or greater). 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 prevent optimization of statin therapy.
