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

Inclusion Criteria: * Provision of signed and dated informed consent form. * Stated willingness to comply with all study procedures and availability for the duration of the study, including potential randomization to injections. * Age \>18 and \<85 years and able to provide self-consent. * Taking five or more prescription drugs at the time of enrollment, of any type. * Meets at least one of the following criteria: * Elevated 10-year ASCVD risk score ≥7.5% (based on the ACC/AHA ASCVD Risk Estimator Plus tool). * Evidence of subclinical atherosclerosis including: Calcification in any vascular bed, including coronary arteries and aorta. Calcification of cardiac valves. Breast calcification. Carotid plaque that is not hemodynamically significant. o Type II diabetes on a stable medical regimen with HbA1c \<8.5%. Per American Diabetes Association guidelines, patients with Type II diabetes aged 40-75 years should be on a moderate-intensity statin. Patients with documented partial or complete statin intolerance are eligible for enrollment. * On maximally tolerated statin therapy (which can be no statin for patients with documented intolerance) and have suboptimal LDL levels: * For patients with Type II diabetes: LDL \>70 mg/dL or non-HDL \>120 mg/dL. * For other patients: LDL \>90 mg/dL or non-HDL \>120 mg/dL. * Willing to adhere to the randomized study regimen, including subcutaneous injection of inclisiran. * Agreement to adhere to lifestyle considerations (see Section 5.3) throughout the study duration. Exclusion Criteria: * Prior or current use of inclisiran. * Known hypersensitivity or allergy to inclisiran or its components. * Active liver disease or unexplained persistent elevations in liver enzymes (ALT or AST \>3x upper limit of normal). * History of rhabdomyolysis or severe muscle-related statin intolerance. * Uncontrolled diabetes (HbA1c \>8.5%). * Active malignancy requiring systemic therapy. * Recent major cardiovascular event (myocardial infarction, stroke, or hospitalization for unstable angina) within the past 3 months. * History of organ transplant other than solid-organ transplant. * Pregnancy or breastfeeding. * Any condition that, in the opinion of the investigator, would make participation unsafe or interfere with study procedures.