A Randomized Study to Evaluate the Effect of an Inclisiran First Implementation Strategy vs Usual Care in Patients with ASCVD and Elevated Low-density Lipoprotein Cholesterol: Rationale and Design of the VICTORION-INITIATE Trial

Lead Author's Financial Disclosures Nothing to disclose. Study Funding Novartis Pharmaceuticals Corporation, East Hanover, NJ. Background/Synopsis Most patients with atherosclerotic cardiovascular disease (ASCVD) have elevated low-density lipoprotein cholesterol (LDL-C). Compared to placebo, inclisiran has been shown to be safe, tolerable, and effective at reducing LDL-C in patients with ASCVD. It is unknown whether an inclisiran first strategy compared to usual care (allowing for changes in lipid-lowering therapy to mimic routine clinical decision-making) can improve LDL-C control in patients with ASCVD when inclisiran is added to statin therapy. Objective/Purpose Describe the rationale and design of the ongoing VICTORION-INITIATE (NCT04929249) trial. Methods VICTORION-INITIATE is a phase 3, randomized, 2-arm, parallel-group, open-label, U.S.-based trial assessing the efficacy of an inclisiran first strategy vs usual care to treat ASCVD. Patients in the inclisiran arm will receive both inclisiran and maximally tolerated statin therapy immediately upon failure to reach LDL-C less than 70 mg/dL with statins alone. Patients in the usual care arm will continue to receive maximally tolerated statin therapy and may receive other non-statin therapies per usual care. Sites were selected based on geography, population, and lipid management practices. The trial will enroll ∼444 patients (aged greater than or equal to 18 years) with established ASCVD and elevated LDL-C (greater than or equal to 70 mg/dL) or non-high-density lipoprotein cholesterol (greater than or equal to 100 mg/dL) despite receiving maximally tolerated statin therapy, fasting triglycerides less than 500 mg/dL, and an estimated glomerular filtration rate greater than 30 mL/min. The study has 6 planned visits over 330 days from screening to completion. Results Primary outcomes are percent change from baseline in LDL-C and proportion of patients discontinuing statins during the 330-day trial. Key secondary outcomes include the proportion of patients achieving prespecified LDL-C targets, proportion of patients achieving greater than or equal to 50% LDL-C reductions, absolute and time-averaged changes in LDL-C, changes in other lipids, changes in and adherence to ongoing lipid-lowering therapy, visit-to-visit variability in LDL-C, and inclisiran safety and tolerability. Conclusions VICTORION-INITIATE is ongoing and planned to complete in early 2023. This trial aims to determine the efficacy of adding inclisiran first when maximally tolerated statin therapy fails to achieve LDL-C less than 70 mg/dL in those with ASCVD. Nothing to disclose.