Inclisiran plus usual care improves LDL-C goal attainment after acute coronary syndrome

Photo by National Cancer Institute / Unsplash

Journal of the American Heart Association Published May 20, 2026 Medically reviewed May 20, 2026 Study authors: Knowlton Kirk U, Navar Ann Marie, Anderson Jeffrey L, Brown Alan S, Muhlestein Joseph B, Kleeman Kel… PubMed ↗ NCT04873934 ↗ DOI ↗ By Dr. Julia Lee, PhD · Oncology, Genomics & Drug Development

Key Takeaway

Consider adding inclisiran early after ACS to improve LDL-C goal attainment, but interpret open-label results cautiously.

This phase 3b open-label randomized controlled trial evaluated inclisiran in 400 patients discharged following acute coronary syndrome (≤5 weeks of screening) with LDL-C ≥70 mg/dL (or non-HDL-C ≥100 mg/dL) despite statin therapy or statin intolerance. Patients received inclisiran sodium 300 mg (284 mg inclisiran equivalent) on Days 0, 90, and 270 plus usual care, or usual care alone (clinician-directed LDL-C management).

At Day 90, 74.6% of inclisiran patients achieved LDL-C <70 mg/dL vs 26.6% with usual care (OR 10.84, 97.5% CI 6.13-19.16). At Day 330, 66.7% vs 28.1% achieved this goal (OR 5.42, 97.5% CI 3.29-8.91, p<0.001). LDL-C percentage change from baseline at Day 330 showed a -46.9% difference favoring inclisiran (97.5% CI -55.4 to -38.5, p<0.001).

Adverse events occurred in 58.6% of inclisiran patients vs 53.3% with usual care. Serious adverse events and discontinuations were not reported. The authors stated inclisiran was well tolerated.

Key limitations include the open-label design, which may introduce bias, and the comparator being usual care rather than placebo. The study was designed to mimic clinical practice, not as a strict efficacy trial. Despite these caveats, early inclisiran initiation with usual care resulted in rapid, sustained attainment of guideline-directed LDL-C goals in patients with recent acute coronary syndrome.

Study Details

Study typeRct

Sample sizen = 400

EvidenceLevel 2

PublishedMay 2026

PMID42132192

TrialNCT04873934

View Original Abstract ↓

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], <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]; <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.