Inter-individual variability in LDL-C reductions with inclisiran – data from ORION-10 and ORION-11
Rattachement africain : us, Afrique du Sud, de, ca, nl, gb. Niveau de preuve : code pays fourni par la source.
Le résumé fourni par la source
Abstract Introduction Inclisiran, an investigational siRNA, has been shown to effectively and durably lower LDL-C in Phase 3 trials. Inter-individual variability in LDL-C reductions has been documented for statin therapy and ezetimibe. Purpose To evaluate the inter-individual variability in LDL-C lowering with inclisiran. Methods The Phase 3 ORION-10 and ORION-11 trials randomized patients with established ASCVD (or risk-equivalents) who had LDL-C >70 mg/dl despite maximally tolerated statins to inclisiran or placebo (1:1). Inclisiran sodium 300 mg was administered s.c. at baseline, three months later, then every six months. Co-primary endpoints were the LDL-C reduction from baseline to Day 510 and the time adjusted average % change in LDL-C reduction after Day 90 and up to Day 540. Measures of response variability were pre-specified secondary endpoints. This analysis examines the inter-individual variability of LDL-C reductions at day 510 using pooled data from both trials. Results The analysis included 3178 individuals (92% on statins). At Day 90, 97% of inclisiran-treated patients had an LDL-C reduction. At Day 510, the median percent reduction in LDL-C levels from baseline was 57.3% in the inclisiran group (interquartile range, 44%-70%). An LDL-C reduction ≥50% was reached by 1359 (86.6%) inclisiran-treated patients versus 97 (6.2%) placebo patients at any visit (odds ratio [OR] 97.6, 95% confidence interval [CI] 76–126). An LDL-C reduction ≥30% was reached by 1523 (97.0%) inclisiran-treated patients versus 371 (23.7%) placebo patients (OR 104.5, 95% CI 76–143). At Day 510, 921 patients (65.1%) in the inclisiran group had a reduction ≥50% in LDL-C compared to 34 patients (2.4%) in the placebo group, and 1228 (86.8%) had a reduction ≥30% compared to 148 (10.5%), respectively. Among placebo-treated patients, there was a substantial proportion with notable increases in LDL-C at Day 510 (figure). Conclusion In Phase 3 trials, inclisiran on top of maximally tolerated statins provided reliable, consistent and durable reductions in LDL-C. A large percentage of subjects randomized to inclisiran achieved substantial reductions (>50%) in LDL-C and nearly all achieved at least a 30% reduction suggesting inclisiran is potentially a promising novel therapy for patients needing sustained LDL-C reductions. Waterfall plot of pooled trials Funding Acknowledgement Type of funding source: Private company. Main funding source(s): The Medicines Company
Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.
Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Inter-individual variability in LDL-C reductions with inclisiran – data from ORION-10 and ORION-11
- Date Crossref
- 01/11/2020
- Éditeur
- Oxford University Press (OUP)
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
-
Mayo Clinic in Florida pays non établi dans la noticeÉtablissement de santé
-
University of the Witwatersrand University of the Witwatersrand, Afrique du Sud (code pays fourni par la source)Université ou école supérieure
-
Doctors Company (United States) pays non établi dans la noticeEntreprise
-
Deutsches Herzzentrum München pays non établi dans la noticeÉtablissement de santé
-
St. Michael's Hospital pays non établi dans la noticeÉtablissement de santé
-
Charité - Universitätsmedizin Berlin pays non établi dans la noticeÉtablissement de santé
-
University of Colorado Health pays non établi dans la noticeÉtablissement de santé
-
Amsterdam University Medical Centers pays non établi dans la noticeÉtablissement de santé
-
Imperial College London pays non établi dans la noticeUniversité ou école supérieure
-
The Medicines Company pays non établi dans la noticeEntreprise
-
German Heart Center of Munich pays non établi dans la noticeInstitution
-
Amsterdam UMC pays non établi dans la noticeInstitution
Mayo Clinic in Florida, University of the Witwatersrand (University of the Witwatersrand, Afrique du Sud) et Doctors Company (United States), avec 9 autres affiliations. Pays d’affiliation : Afrique du Sud.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.