Inclisiran vs bempedoic acid for low-density lipoprotein cholesterol lowering in high-risk patients: the VICTORION-Challenge trial.

BACKGROUND AND AIMS: Low-density lipoprotein cholesterol (LDL-C) targets remain unmet in many high-risk atherosclerotic cardiovascular disease (ASCVD) patients on statins (± ezetimibe). VICTORION-Challenge compared inclisiran with bempedoic acid (BPA) for LDL-C lowering and target attainment in these patients, directly. METHODS: In this phase 4, open-label study, ASCVD patients with LDL-C ≥70 mg/dL on statins (± ezetimibe) were randomized to inclisiran or BPA. The primary endpoint was percentage change in LDL-C at Day 150; key secondary endpoints at Day 150 included percentage LDL-C change stratified by ezetimibe use. Secondary endpoints included LDL-C goal attainment and absolute change; treatment-emergent adverse events (TEAEs) were evaluated. RESULTS: Among 402 randomized patients (mean±standard deviation age, 63.1±10.7 years; 64.2% men; baseline LDL-C 94.4±28.3 mg/dL), LDL-C reduction at Day 150 was superior with inclisiran vs BPA (least squares mean -56.3% vs -15.4%; between-group difference -41.0%, 95% confidence interval [CI] -45.7 to -36.2; p<0.0001). Inclisiran achieved greater absolute LDL-C reduction at Day 150 (-53.4 vs -17.5 mg/dL) regardless of ezetimibe use, with higher LDL-C goal attainment (78.2% vs 20.3%; adjusted odds ratio 16.36, 95% CI 9.72 to 27.54; descriptive p<0.0001). Inclisiran showed a favourable safety profile vs BPA, with comparable rates of TEAEs (63.1% vs 59.8%) and serious TEAEs (5.9% vs 7.5%). Most common TEAEs (inclisiran vs BPA) included nasopharyngitis (10.3% vs 7.5%), hypertension (4.9% vs 4.5%), and myalgia (3.4% vs 5.5%). One non-treatment-related death (inclisiran) was reported. CONCLUSIONS: Inclisiran provided superior LDL-C reduction versus BPA with favourable safety, supporting its use in high-risk patients not achieving guideline-recommended goals.