Inclisiran on top of individually optimized lipid-lowering therapy helped more patients with hypercholesterolemia at high/very high risk of cardiovascular events achieve LDL cholesterol (LDL-C) goals compared with placebo, based on findings from the VICTORION-Difference trial presented at ESC Congress 2025.

The trial, which was conducted at 133 centers in Bulgaria, Czechia, Estonia, France, Germany, Latvia, Poland and Spain, randomized 1,770 patients 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 mg/day or 10 mg/day) was sequentially and optimally titrated to the maximally tolerated dose if individual LDL-C goals were not achieved, according to study investigators.

A significantly higher proportion of participants in the inclisiran group (84.9%) compared with the placebo group (31%) achieved their individual guideline-recommended LDL-C goals at 90 days – the primary endpoint. Time-averaged mean percentage LDL-C reductions from baseline to day 360 were −59.45% in the inclisiran group and −24.31% in the placebo groups. The incidence of treatment-emergent adverse events was similar between the inclisiran and placebo groups.

"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," said Ulf Landmesser, MD, in presenting the results. "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."