{"id":"doi:10.1093/eurheartj/ehaf685","kind":"article","title":"Inclisiran-based treatment strategy in hypercholesterolaemia: the VICTORION-difference trial","authors":["Landmesser U","Laufs U","Schatz U","Winzer EB","Nowak B","Kassner U","Gouni-Berthold I","Esteban A","Lubyayi L","Krueger A","Hentschke C","Wilke A","Winkelmann BR","Achouba A","Banach M"],"author_count":15,"year":2026,"published":"2026-07-01","venue":"European heart journal","cited_by":10,"doi":"10.1093/eurheartj/ehaf685","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1093/eurheartj/ehaf685","archive_url":"https://space-kitty.com/papers/doi:10.1093/eurheartj/ehaf685","updated":null,"pmid":"40884558","pmcid":"PMC13318417","openalex_id":null,"pdf_url":"https://europepmc.org/articles/PMC13318417/pdf","abstract":"Background and aims Low-density lipoprotein cholesterol (LDL-C) is a causal risk factor for atherosclerotic cardiovascular (CV) disease development and progression. The European Society of Cardiology guidelines recommend combination treatment to achieve CV risk-based LDL-C treatment goals. Inclisiran, a small interfering ribonucleic acid (siRNA) that targets hepatic proprotein convertase subtilisin/kexin type 9 (PCSK9) messenger RNA, can provide sustained and effective LDL-C reduction. Methods VICTORION-Difference, a phase 4 double-blind, placebo-controlled randomized clinical trial included adults with hypercholesterolaemia at high- or very high CV risk. Participants were randomized 1:1 to receive inclisiran sodium (300 mg subcutaneous injections; equivalent to 284 mg inclisiran) or placebo together with individually optimized lipid-lowering therapy (ioLLT), including up-titration with rosuvastatin (open-label) until either their individual LDL-C goal or maximally tolerated statin dose (open-label rosuvastatin) was achieved. The primary objective was assessment of LDL-C goal achievement at Day 90. Key secondary objectives were muscle-related adverse events (MRAEs) and mean LDL-C reduction. Overall, 1770 individuals (mean age, 63.7 years) were randomized to receive inclisiran (n = 898) or ioLLT (n = 872). At Day 90, a significantly higher proportion of participants receiving inclisiran vs. ioLLT achieved their individual LDL-C goals [84.9% vs 31.0%; odds ratio (OR) 12.09, P < .001]. The mean percentage reduction in LDL-C from baseline to Day 360 was -59.5% and -24.3% in the inclisiran and ioLLT arms, respectively [least squares mean treatment difference (LSMTD) = -35.14%, P < .001]. Fewer participants receiving inclisiran vs ioLLT reported a MRAE (11.9% vs 19.2%; OR 0.57, P < .001). The mean reduction in Short Form-Brief Pain Inventory pain severity and interference scores favoured inclisiran over ioLLT (LSMTD = -0.11, P = .039; LSMTD = -0.11, P = .029, respectively). No new safety concerns were identified. Results Overall, 1770 individuals (mean age, 63.7 years) were randomized to receive inclisiran (n=898) or ioLLT (n=872). At Day 90, a significantly higher proportion of participants receiving inclisiran vs. ioLLT achieved their individual LDL-C goals (84.9% vs. 31.0%; odds ratio [OR] 12.09, p<0.001). The mean percentage reduction in LDL-C from baseline to Day 360 was -59.5% and -24.3% in the inclisiran and ioLLT arms, respectively (least squares mean treatment difference [LSMTD]=-35.14%, p<0.001). Fewer participants receiving inclisiran vs. ioLLT reported a MRAE (11.9% vs. 19.2%; OR 0.57, p<0.001). The mean reduction in Short Form-Brief Pain Inventory pain severity and interference scores favoured inclisiran over ioLLT (LSMTD=-0.11, p=0.039; LSMTD=-0.11, p=0.029, respectively). No new safety concerns were identified. Conclusions An inclisiran-based treatment strategy was superior to ioLLT in LDL-C goal achievement, delivering early and sustained LDL-C reduction, with fewer MRAEs in individuals with hypercholesterolaemia.","abstract_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":[],"details":null,"provenance":"europepmc","attribution":"Abstract of \"Inclisiran-based treatment strategy in hypercholesterolaemia: the VICTORION-difference trial\" by Landmesser U, Laufs U, Schatz U et al., https://doi.org/10.1093/eurheartj/ehaf685, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified.","topics":[{"slug":"cardiovascular-innovation","name":"Cardiovascular Therapeutics","domain_slug":"medicine"}],"cited_in_dossiers":[]}