{"id":"3d9ce63b0091","type":"article","url":"https://hartvaat.nl/2020/04/16/inclisiran-fase-3-bij-verhoogd-ldl-nejm-orion-10-en-orion-11/","title":"Inclisiran fase 3 bij verhoogd LDL: NEJM ORION-10 en ORION-11","title_en":"Two Phase 3 Trials of Inclisiran in Patients with Elevated LDL Cholesterol.","category":"cholesterol","category_label":"Cholesterol","professions":["apotheker","cardioloog","huisarts","internist"],"tags":["dyslipidemie","ezetimibe","ldl-cholesterol","lipidenverlaging","niet-statine-therapie","pcsk9-remmers","soul-trial","statines"],"journal":"The New England journal of medicine","doi":"10.1056/NEJMoa1912387","source_url":"https://doi.org/10.1056/NEJMoa1912387","authors":["Kausik K Ray","R Scott Wright","David Kallend","Wolfgang Koenig","Lawrence A Leiter","Frederick J Raal","Jenna A Bisch","Tara Richardson","Mark Jaros","Peter L J Wijngaard","John J P Kastelein"],"significance":10,"published":"2020-04-16","source_date":"2020-04-16","image":"","kennis":["https://hartvaat.nl/kennis/lipiden/inclisiran-sirna/","https://hartvaat.nl/kennis/lipiden/dyslipidemie-overzicht/"],"congress":"","summary_en":"The ORION-10 and ORION-11 phase 3 trials demonstrated that twice-yearly subcutaneous inclisiran reduced LDL cholesterol by approximately 50% with sustained efficacy and an acceptable safety profile. These results confirmed inclisiran as a viable long-acting approach to LDL lowering, offering an alternative to frequent dosing with statins or monoclonal antibodies.","created":"2026-07-03T10:28:31Z","updated":"2026-07-03T13:27:41Z","licence":"Citeer vrij, met bronvermelding en een link naar hartvaat.nl (de url van het record). Samenvattingen zijn redactioneel werk van HartVaat; de oorspronkelijke publicaties blijven van hun uitgevers (doi). Geen medisch advies.","body_markdown":"NEJM publicatie van twee fase-3-trials (ORION-10 en ORION-11) die aantoonden dat tweemaal jaarlijks inclisiran het LDL-cholesterol met ~50% verlaagt. Definitief bewijs voor siRNA-lipidentherapie.","abstract_original":"BACKGROUND: Inclisiran inhibits hepatic synthesis of proprotein convertase subtilisin-kexin type 9. Previous studies suggest that inclisiran might provide sustained reductions in low-density lipoprotein (LDL) cholesterol levels with infrequent dosing. METHODS: We enrolled patients with atherosclerotic cardiovascular disease (ORION-10 trial) and patients with atherosclerotic cardiovascular disease or an atherosclerotic cardiovascular disease risk equivalent (ORION-11 trial) who had elevated LDL cholesterol levels despite receiving statin therapy at the maximum tolerated dose. Patients were randomly assigned in a 1:1 ratio to receive either inclisiran (284 mg) or placebo, administered by subcutaneous injection on day 1, day 90, and every 6 months thereafter over a period of 540 days. The coprimary end points in each trial were the placebo-corrected percentage change in LDL cholesterol level from baseline to day 510 and the time-adjusted percentage change in LDL cholesterol level from baseline after day 90 and up to day 540. RESULTS: A total of 1561 and 1617 patients underwent randomization in the ORION-10 and ORION-11 trials, respectively. Mean (±SD) LDL cholesterol levels at baseline were 104.7±38.3 mg per deciliter (2.71±0.99 mmol per liter) and 105.5±39.1 mg per deciliter (2.73±1.01 mmol per liter), respectively. At day 510, inclisiran reduced LDL cholesterol levels by 52.3% (95% confidence interval [CI], 48.8 to 55.7) in the ORION-10 trial and by 49.9% (95% CI, 46.6 to 53.1) in the ORION-11 trial, with corresponding time-adjusted reductions of 53.8% (95% CI, 51.3 to 56.2) and 49.2% (95% CI, 46.8 to 51.6) (P<0.001 for all comparisons vs. placebo). Adverse events were generally similar in the inclisiran and placebo groups in each trial, although injection-site adverse events were more frequent with inclisiran than with placebo (2.6% vs. 0.9% in the ORION-10 trial and 4.7% vs. 0.5% in the ORION-11 trial); such reactions were generally mild, and none were severe or persistent. CONCLUSIONS: Reductions in LDL cholesterol levels of approximately 50% were obtained with inclisiran, administered subcutaneously every 6 months. More injection-site adverse events occurred with inclisiran than with placebo. (Funded by the Medicines Company; ORION-10 and ORION-11 ClinicalTrials.gov numbers, NCT03399370 and NCT03400800.)."}