Randomized Double-Blind Comparison of Apixaban with Enoxaparin for Thromboprophylaxis after Knee Replacement: The ADVANCE-1 Trial
Notice bibliographique
Résumé
Abstract Thromboprophylaxis with enoxaparin after total knee replacement is an evidence-based recommended standard of care. The ADVANCE-1 clinical trial was a phase III randomized double-blind multicenter study that evaluated the efficacy and safety of apixaban, an oral direct factor Xa inhibitor, 2.5 mg orally bid compared with enoxaparin 30 mg subcutaneously every 12 hours for preventing venous thromboembolism after total knee replacement. Apixaban (or oral placebo) and enoxaparin (or subcutaneous placebo) were begun 12 to 24 hours post-operatively (mean 20 hours) and continued until mandatory bilateral venography was completed at 12± 2 days. The primary efficacy outcome was the composite of deep-vein thrombosis (DVT) by venography; symptomatic, objectively confirmed DVT or pulmonary embolism (PE); or death from any cause during the treatment period. The secondary efficacy outcome was the composite of objectively confirmed proximal DVT or PE, or death. The primary safety outcome was bleeding, including major bleeding (defined by ISTH criteria), clinically relevant non-major bleeding, and minor bleeding. All outcome events were interpreted by a central independent adjudication committee without knowledge of treatment. The study hypothesis was that apixaban would be as effective as enoxaparin based on a pre-specified non-inferiority margin in which the upper limit of the two-sided 95% CI is < 1.25 for relative risk and < 5.6% for the absolute risk difference for the primary efficacy outcome. A total of 3195 patients from 129 sites in 14 countries were randomized. The primary efficacy outcome occurred in 104 of 1157 patients (8.99%) given apixaban and in 100 of 1130 (8.85%) given enoxaparin (relative risk 1.02, 95% CI 0.78 to 1.32, one-sided p= 0.064 for non-inferiority, statistical criteria not met). The secondary efficacy outcome occurred in 26 patients (2.05%) given apixaban and in 20 patients (1.64%) given enoxaparin. Symptomatic PE occurred in 16 patients (1.0%) who received apixaban (2 fatal) and in 7 patients (0.44%) given enoxaparin (0 fatal); the majority of the PE in apixaban patients occurred within 48 hours postoperatively. Major or clinically relevant non-major bleeding occurred in 46 of 1596 patients (2.88%) given apixaban, compared with 68 patients (4.28%) given enoxaparin (absolute difference 1.46%, two-sided p=0.034). Major bleeding occurred in 11patients (0.69%) who received apixaban and in 22 patients (1.39%) who received enoxaparin (two-sided p=0.053). Elevated levels of liver transaminase enzymes were uncommon (2% to 3%) in both groups; no patient given apixaban met Hy’s criteria. Myocardial infarction or stroke occurred in only one patient who received apixaban (0.06%) and in 5 patients (0.31%) given enoxaparin. The lower-than-expected incidence of the primary efficacy outcome in the enoxaparin group resulted in an undersized study to meet the pre-defined statistical criteria for non-inferiority in spite of a similar incidence with the apixaban regimen. This is the first phase III trial to demonstrate a potential advantage of the new oral anticoagulants for bleeding. The apixaban regimen resulted in less clinically relevant bleeding than enoxaparin 30 mg given every 12 hours. Maintaining this advantage while optimizing efficacy with an altered dosing regimen, either by earlier postoperative dosing or by a slightly increased dose, would be an important advance in patient care.
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 | 0,004 | 0,005 |
| Méta-épidémiologie (sens strict) | 0,003 | 0,002 |
| Méta-épidémiologie (sens large) | 0,008 | 0,004 |
| Bibliométrie | 0,001 | 0,001 |
| Études des sciences et des technologies | 0,001 | 0,002 |
| Communication savante | 0,002 | 0,002 |
| Science ouverte | 0,002 | 0,001 |
| Intégrité de la recherche | 0,004 | 0,004 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,013 | 0,002 |
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 ».