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.