Low‐Density Lipoprotein Cholesterol Lowering With Inclisiran Plus Usual Care in Recent Acute Coronary Syndrome: VICTORION‐INCEPTION, a Randomized, Controlled, Open‐Label Trial

Background The low‐density lipoprotein cholesterol (LDL‐C)‐lowering effect of inclisiran, a proprotein convertase subtilisin/kexin type 9‐targeting small interfering RNA, has not been established in patients with recent acute coronary syndrome. Methods VICTORION‐INCEPTION, a 330‐day, phase 3b, open‐label, multicenter trial, designed to mimic clinical practice, randomized 400 eligible participants (discharged following acute coronary syndrome ≤5 weeks of screening, with LDL‐C ≥70 mg/dL or non–high‐density lipoprotein cholesterol ≥100 mg/dL, receiving statin therapy or statin intolerant) 1:1 to inclisiran sodium 300 mg (284 mg inclisiran equivalent; Days 0, 90, 270) + usual care, or usual care (clinician‐directed LDL‐C management). Coprimary end points at Day 330 were LDL‐C <70 mg/dL attainment and LDL‐C percentage change from baseline. Results At Day 90, inclisiran + usual care led to greater LDL‐C goal attainment and lowering versus usual care (<70 mg/dL: 74.6% versus 26.6%, odds ratio OR, 10.84 97.5% CI, 6.13–19.16; <55 mg/dL: 63.2% versus 8.5%, OR, 26.58 95% CI, 14.14–49.98; percentage change from baseline: −48.9% versus 2.2%); this was sustained to Day 330 (<70 mg/dL: 66.7% versus 28.1%, OR, 5.42 97.5% CI, 3.29–8.91, P <0.001; <55 mg/dL: 54.2% versus 13.6%, OR, 8.24 95% CI, 4.97–13.65; percentage change: −46.9% difference 97.5% CI, −55.4 to −38.5; P <0.001). Participants with ≥1 adverse events were comparable (inclisiran + usual care, 58.6%; usual care, 53.3%). Conclusions VICTORION‐INCEPTION was the first inclisiran trial in participants with recent acute coronary syndrome. Early inclisiran initiation with usual care resulted in rapid, sustained attainment of guideline‐directed LDL‐C goals and was well tolerated. Registration URL: https://clinicaltrials.gov ; Unique identifier: NCT04873934.