Design of VICTORION-2 Prevent: a randomized double-blind, placebo-controlled trial, assessing the impact of inclisiran on major adverse cardiovascular events in patients with established cardiovascular disease

Rationale Inclisiran is a small interfering ribonucleic acid targeting hepatic proprotein convertase subtilisin/kexin type 9 messenger RNA, that effectively reduces low-density lipoprotein cholesterol (LDL-C) levels. The effect of inclisiran on cardiovascular (CV) outcomes has not been formally tested. Methods VICTORION-2 Prevent (NCT05030428) is an ongoing, Phase 3 randomized, double-blind, placebo-controlled, international trial assessing the efficacy and safety of inclisiran in preventing CV events in patients with established atherosclerotic cardiovascular disease (ASCVD) receiving high-intensity statin therapy. Patients with established ASCVD (history of myocardial infarction [MI], ischemic stroke, or symptomatic peripheral artery disease), and fasting plasma LDL-C ≥1.8 mmol/L (70 mg/dL) despite high-intensity statin therapy (≥20 mg rosuvastatin or ≥40 mg atorvastatin daily) will be enrolled. Patients will be treated with inclisiran sodium 300 mg or placebo, administered subcutaneously at Day 1, Day 90, and every 6 months thereafter. The primary outcome will include time to first occurrence of 3-point major adverse CV events (3P-MACE; composite of CV death, MI, or ischemic stroke). Secondary outcomes will include time to occurrence of CV death, time to first occurrence of 4P-MACE (composite of 3P-MACE and urgent revascularization), and major adverse limb event (all adjudicated outcomes), time to occurrence of all-cause death, and long-term safety of inclisiran. Safety will be monitored using a selective safety data collection strategy. Conclusion VICTORION-2 Prevent will provide robust data on CV benefits and safety of inclisiran in patients with established ASCVD and not at guideline-recommended LDL-C goals despite high-intensity statin treatment.