{"id":"doi:10.1093/cvr/cvae109","kind":"article","title":"Inclisiran administration potently and durably lowers LDL-C over an extended-term follow-up: the ORION-8 trial","authors":["Wright RS","Raal FJ","Koenig W","Landmesser U","Leiter LA","Vikarunnessa S","Lesogor A","Maheux P","Talloczy Z","Zang X","Schwartz GG","Ray KK"],"author_count":12,"year":2024,"published":"2024-10-01","venue":"Cardiovascular research","cited_by":78,"doi":"10.1093/cvr/cvae109","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1093/cvr/cvae109","archive_url":"https://space-kitty.com/papers/doi:10.1093/cvr/cvae109","updated":null,"pmid":"38753448","pmcid":"PMC11481169","openalex_id":null,"pdf_url":"https://europepmc.org/articles/PMC11481169/pdf","abstract":"Aims Data describing the long-term efficacy and tolerability of inclisiran are limited. This was explored in ORION-8, an open-label extension of preceding Phase 2 and Phase 3 placebo-controlled and open-label extension trials. Methods and results Following completion of the parent trial, adult patients with atherosclerotic cardiovascular disease (ASCVD), ASCVD risk equivalent, or heterozygous familial hypercholesterolaemia received open-label inclisiran twice yearly (after initial and 3-month doses) until Day 990, followed by an end-of-study visit at Day 1080 or ≥ 90 days after the last dose. The study endpoints included the proportion of patients achieving pre-specified low-density lipoprotein cholesterol (LDL-C) goals [ASCVD: < 1.8 mmol/L (< 70 mg/dL); ASCVD risk equivalent: < 2.6 mmol/L (< 100 mg/dL)], percentage and absolute changes in LDL-C at end-of-study, and safety of inclisiran. Of 3274 patients, 2446 (74.7%) were followed until end-of-study. Mean age was 64.9 ± 9.9 years, 82.7% (n = 2709) had ASCVD, and mean baseline LDL-C was 2.9 ± 1.2 mmol/L. Mean cumulative exposure to inclisiran (including parent trials) was 3.7 years; maximum exposure was 6.8 years. With inclisiran, 78.4% [95% confidence interval (CI): 76.8, 80.0] of patients achieved pre-specified LDL-C goals and mean percentage change in LDL-C was -49.4% (95% CI: -50.4, -48.3). No attenuation of LDL-C lowering over time was observed. Treatment-emergent adverse events at injection site (all mild/moderate) occurred in 5.9% of the patients. Inclisiran-associated anti-drug antibodies were infrequent (5.5%) and had no impact on the efficacy or safety of inclisiran. No new safety signals were identified. Conclusion In the largest and longest follow-up to date with >12 000 patient-years exposure, inclisiran demonstrated consistent and effective LDL-C lowering with a favourable long-term safety and tolerability profile. Trial registration number ClinicalTrials.gov identifier: NCT03814187.","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 administration potently and durably lowers LDL-C over an extended-term follow-up: the ORION-8 trial\" by Wright RS, Raal FJ, Koenig W et al., https://doi.org/10.1093/cvr/cvae109, 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":[]}