Hot Line 4: VICTORION-Difference
31 Aug 2025
Hot Line ESC Congress 2025 Inclisiran in patients with hypercholesterolaemia at high CV risk: VICTORION-Difference
Professor Ulf Landmesser (Deutsches Herzzentrum der Charité - Berlin, Germany) explained the aims of the VICTORION-Difference trial: “When given subcutaneously every 3 or 6 months, inclisiran interferes with PCSK9 production, decreasing low-density lipoprotein cholesterol (LDL-C) levels. The purpose of the VICTORION-Difference study was to compare inclisiran with placebo, on top of individually optimised lipid-lowering therapies, for LDL-C goal achievement and novel endpoints related to muscle-related adverse events and pain-related quality of life in a population that mirrors real-world practice.”
In this double-blind phase IV trial, patients at high or very high CV risk according to 2019 ESC/EAS guidelines and with elevated LDL-C despite maximally tolerated statins were randomised to receive either subcutaneous injections of inclisiran sodium 300 mg (equivalent to 284 mg inclisiran) or placebo. In addition to inclisiran/placebo, open-label rosuvastatin (starting dose of 5 or 10 mg/day) was sequentially and optimally titrated to the maximally tolerated dose if LDL-C goals were not achieved. The primary endpoint was the proportion of participants achieving 2019 guideline-recommended LDL-C goals (very high CV risk: <55 mg/dl [<1.4 mmol/l]; high CV risk: <70 mg/dl [<1.8 mmol/l]) at day 90.
A significantly higher proportion of participants in the inclisiran vs. standard-care arm achieved LDL-C goals at 90 days: 84.9% vs. 31.0% (p<0.0001).
Time-averaged mean percentage LDL-C reductions from baseline to day 360 were –59.45% and –24.31% in the inclisiran and the standard-care groups, respectively (least squares mean treatment difference 35.14%; p<0.0001). Fewer participants with inclisiran vs. standard care experienced a muscle-related adverse event (11.9% vs. 19.2%; p<0.0001). In addition, numerically larger time-averaged reductions were noted with inclisiran vs. standard care for pain-related severity (–0.11; p=0.0389) and interference scores (–0.11; p=0.0285) using the Short-Form Brief Pain Inventory, which did not reach statistical significance.
In conclusion, Prof. Landmesser commented: “This large study demonstrated the effectiveness of an inclisiran-based treatment strategy over current usual care in bringing patients to early and sustained LDL-C goals, with significantly fewer adverse muscle symptoms. These findings indicate that inclisiran represents a convenient, effective and well-tolerated treatment option for the high number of at-risk patients who currently do not respond adequately to other lipid-lowering therapies.”
