Evolocumab treatment reduces carotid intima-media thickness in paediatric patients with heterozygous familial hypercholesterolaemia
Notice bibliographique
Résumé
Abstract Background Familial hypercholesterolemia (FH) is characterised by high plasma levels of low-density lipoprotein cholesterol (LDL-C) and increased risk of premature atherosclerotic cardiovascular disease (ASCVD). Previous studies show that carotid intima-media thickness (cIMT) is increased in children with FH, an indicator of early ASCVD. Add-on treatment with the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, evolocumab, substantially reduced atherosclerotic lipid levels in children with heterozygous FH (HeFH) and was safe and well tolerated. The effect of evolocumab on cIMT in paediatric patients (pts) has not been investigated. Purpose To investigate the effect of evolocumab treatment on cIMT progression in paediatric pts with HeFH. Methods HAUSER-RCT was a multicenter, randomised, placebo-controlled study in which paediatric FH pts (ages 10–17 years) received monthly subcutaneous injections of evolocumab 420 mg or placebo. Of 157 pts, 150 continued to an open-label extension study (HAUSER-OLE) during which all received up to 80 weeks of monthly evolocumab 420 mg on top of stable background statin therapy. cIMT was measured by B-mode ultrasound scanning at baseline, week 24 of the RCT, and weeks 24, 48, and 80 of the OLE. cIMT was measured on anterior, lateral, and posterior imaging angles of the right and left common carotid artery. Mean thickness at each visit and mean changes from baseline were summarised by treatment received during the RCT and artery location. In addition, the largest measurements (anterior, lateral, or posterior) from a patient's left and right carotid artery were averaged to calculate a summary score. Results Mean baseline cIMT summary score was 0.568 mm (SD=0.06) for 46 placebo pts and 0.586 mm (SD=0.06) for 82 evolocumab pts. During the RCT, 37 placebo pts had a mean increase of 0.006 mm (SD=0.05) from baseline to week 24; in contrast, 76 evolocumab pts had a mean decrease of 0.003 mm (SD=0.05). Although this treatment group difference was not statistically significant (P=0.403), the pattern of increased cIMT for placebo and decreased cIMT for evolocumab was consistent across artery locations (Table). During the OLE, for pts who initially received placebo, mean cIMT summary score decreased by 0.019 mm (SD=0.04, n=34) from baseline to week 80 (P=0.007) (Figure). Pts who received evolocumab in both the RCT and OLE showed continued improvement during the OLE; at week 80, mean cIMT summary score decreased by 0.012 mm (SD=0.05, n=59) from baseline (P=0.067). For all pts at week 80 (n=128), the mean decrease in LDL-C from baseline was 35.3% (SD=28.0). Conclusions Open-label evolocumab treatment for up to 80 weeks led to reductions in mean cIMT. In this small sample of pts with FH, the data suggest that the addition of PCSK9 inhibition to background lipid-lowering therapy has the potential to reduce the risk of ASCVD progression and future cardiovascular events in this vulnerable paediatric population. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Amgen, Inc.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».