Bleeding Outcomes in Patients with Gastrointestinal Malignancies Treated with Distally Absorbed Versus Proximally Absorbed Direct Oral Anticoagulants
Notice bibliographique
Résumé
Abstract Introduction: Randomized trials comparing direct oral anticoagulants (DOACs) to low molecular weight heparin demonstrated higher rates of bleeding associated with DOACs, especially in patients with gastrointestinal (GI) malignancies. DOACs differ in location of absorption with apixaban predominately absorbed in the distal small bowel and proximal colon and edoxaban, rivaroxaban and dabigatran absorbed in the proximal GI tract (e.g. stomach and proximal small intestine). No comparative data is available for the DOACs in treatment of cancer-associated thrombosis (CAT). Given the differences in location of absorption, we aimed to assess the association of bleeding in patients with GI malignancy and CAT on apixaban versus those treated with proximally absorbed DOACs (dabigatran, edoxaban, or rivaroxaban). Methods: Using a nationwide cohort of Veterans, we identified patients with active GI malignancy between 2012 and 2018. Using a previously validated algorithm (91% positive predictive value), we identified patients with newly diagnosed VTE. A VTE was considered to occur in the setting of active cancer if the diagnosis occurred (1) within 3 months before cancer diagnosis, (2) within 6 months after cancer diagnosis, or (3) any time after diagnosis of metastatic cancer. We limited the cohort to patients who received at least a 30-day prescription for anticoagulant therapy with apixaban, dabigatran, edoxaban or rivaroxaban. Patients with a prescription for any anticoagulant therapy within 6 months before VTE diagnosis were excluded. We retrospectively followed patients to 30-days after the last DOAC prescription or to death, whichever came first. The primary outcome of interest was clinically significant bleeding while on DOAC therapy. We defined clinically significant bleeding as the presence of an ICD-9 or ICD-10 code for bleeding in any position for an inpatient admission with 3 exceptions: microscopic hematuria, bleeding related to major trauma and metromenorrhgia. We assessed the association between DOAC use and bleeding as a time-to-event outcome while adjusting for the competing risk of non-bleeding related death through the methods of Fine and Gray. Results: Between 2012 and 2018, a total of 215 patients with GI malignancies received a DOAC for treatment of CAT. Eighty-six patients received apixaban and the remaining 129 received a proximally absorbed DOAC with the majority receiving rivaroxaban (80%). Baseline demographics by anticoagulant therapy are listed in Table 1. None of the clinical variables assessed were significantly different between patients on apixaban versus a proximally absorbed DOAC, including variables associated with risk of anticoagulant-related bleeding. Of the 215 patients included, 73% were diagnosed with a distal GI malignancy (colon or lower). During the follow-up period, 43 of 215 patients (20%) experienced a clinically significant bleeding event, 22.1% of patients on apixaban and 18.6% of patients on a proximally absorbed DOAC. Of the 43 bleeding events, 30 were bleeding from the GI tract. In patients on apixaban versus a proximally absorbed DOAC, there was no significant difference in the risk of clinically significant bleeding (hazard ratio (HR) 1.24; 95% confidence interval (CI): 0.67 - 2.21). Similarly, there was no significant difference in the risk of bleeding from the GI tract in patients on apixaban versus a proximally absorbed DOAC (HR 0.90; 95% CI: 0.43 - 1.89). Conclusion: In this study of 215 patients with GI malignancy, we found no significant difference in the risk of bleeding between patients treated with apixaban versus those treated with a proximally absorbed DOAC. The rate of clinically significant bleeding was high (20%) while on DOAC therapy. There is a continued need for future prospective studies evaluating antithrombotic therapy in patients with GI malignancies and CAT. Figure 1 Figure 1. Disclosures Sanfilippo: AstraZeneca: Research Funding; Atellas Pharma Global: Research Funding. Wang: Servier: Membership on an entity's Board of Directors or advisory committees; Leo Pharma: Research Funding.
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 | 0,001 | 0,002 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,001 |
| Bibliométrie | 0,000 | 0,001 |
| 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 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 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 ».