{"id":"doi:10.1007/s11739-026-04417-8","kind":"article","title":"Real-world lipid outcomes after switching PCSK9-targeting therapies in heterozygous familial hypercholesterolemia: the SHIFT-FH study","authors":["Calcaterra IL","De Luca C","Valletta LJ","D'Errico G","Ferrandino M","Cardiero G","Di Taranto MD","Fortunato G","Iannuzzo G","Tufano A","Di Minno M"],"author_count":11,"year":2026,"published":"2026-06-13","venue":"Internal and emergency medicine","cited_by":0,"doi":"10.1007/s11739-026-04417-8","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1007/s11739-026-04417-8","archive_url":"https://space-kitty.com/papers/doi:10.1007/s11739-026-04417-8","updated":null,"pmid":"42287585","pmcid":"PMC13694442","openalex_id":null,"pdf_url":"https://europepmc.org/articles/PMC13694442/pdf","abstract":"Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition represents a cornerstone of lipid-lowering therapy in heterozygous familial hypercholesterolemia (HeFH). Monoclonal antibodies (mAbs) and small interfering RNA (siRNA) targeting PCSK9 provide complementary therapeutic strategies; however, real-world data comparing lipid outcomes and target achievement after switching between these treatments remain limited. The SHIFT-FH study was a retrospective real-world cohort study including genetically confirmed HeFH patients receiving maximally tolerated lipid-lowering therapy and stable PCSK9 monoclonal antibody treatment for ≥ 6 months. According to routine clinical practice, patients either switched to siRNA therapy (inclisiran; Group 1) or continued monoclonal antibody therapy (Group 2). The primary outcome was achievement of guideline-recommended LDL-C targets at 6 and 12 months. Secondary outcomes included changes in lipid parameters and hepatic safety. Forty-eight patients were included (22 in Group 1 and 26 in Group 2; mean age 59.3 ± 12.8 years). At baseline, LDL-C target achievement was lower in patients subsequently switched to siRNA therapy (36.4% vs 80.8%; p = 0.002). At 12 months, target attainment remained lower in Group 1 (22.7% vs 53.8%). Switching to siRNA therapy was associated with a moderate increase in LDL-C levels (Δ + 29.6 ± 37.4 mg/dL; p = 0.003), whereas lipid levels remained stable in patients continuing monoclonal antibody therapy. Exploratory analysis suggested a trend toward an inverse association between baseline LDL-C levels and target achievement at follow-up. Liver enzymes remained within the normal range in both groups. In this real-world cohort of genetically confirmed HeFH patients, LDL-C target achievement was strongly influenced by baseline lipid burden and differed across therapeutic pathways. Switching between PCSK9-targeting strategies may influence long-term lipid control, highlighting the importance of individualized, target-oriented lipid management.","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 \"Real-world lipid outcomes after switching PCSK9-targeting therapies in heterozygous familial hypercholesterolemia: the SHIFT-FH study\" by Calcaterra IL, De Luca C, Valletta LJ et al., https://doi.org/10.1007/s11739-026-04417-8, 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":[]}