An Evaluation of Andexanet Alfa v. Standard of Care for Reversal of Doac-Induced Intracranial Hemorrhage - a Systematic Review and Meta-Analysis
Notice bibliographique
Résumé
Background Direct oral anticoagulants (DOACs) are reversible factor X inhibitors used to treat and prevent thrombotic complications such as venous thromboembolism and stroke in patients with atrial fibrillation. While offering benefits over traditional anticoagulants, they continue to present the risk of bleeding events, including intracranial hemorrhage (ICH). A recombinant form of factor Xa, Andexanet alfa, is available in some jurisdictions to reverse DOAC effects in patients with life-threatening or uncontrolled bleeding. Previous studies, including a recently published randomised controlled trial (RCT) have observed improvements in hemostatic efficacy and reductions in anti-factor Xa activity compared with “standard of care”. However, pooled efficacy, thrombotic events, and the impact on 30-day mortality reduction is unclear. Objective We performed a systematic review and meta-analysis to determine hemostatic efficacy, thrombotic complications, and mortality in ICH patients receiving Andexanet alfa compared to standard of care. Methods We searched Ovid Medline, EMBASE, CINAHL, and the reference lists of eligible publications for relevant studies published until June 7th, 2024 using a librarian-approved search strategy. Studies were included if they were a prospective or retrospective cohort study or randomized controlled trial (RCT) enrolling more than 15 patients that directly compared Andexanet alfa to standard of care options, as defined by the study, in the context of DOAC-induced ICH. The primary efficacy outcome was hemostatic efficacy, as defined by individual studies. Primary safety outcomes included rates of thrombotic complications, both venous and arterial, and mortality. Secondary outcomes included subgroup analyses of different standard-of-care options. The Review Manager (RevMan) tool, version 7.14.1, was used to pool outcome rates and calculate Mantel-Haenszel (M-H) risk ratios using a random effects model. Results A total of 2423 records were screened, with a total of 22 studies (n = 4330 patients) included in this analysis. Twenty (90.9%) studies were retrospective cohort studies, one (4.5%) was a randomized controlled trial, and one (4.5%) was an analysis of two prospective cohort studies. Eighteen (81.8%) studies predominately or exclusively used 4-factor prothrombin complex concentrate (4F-PCC) as the standard of care, 4 (18.2%) studies used 3-factor and activated PCC, one examined fresh frozen plasma (FFP), and one examined tranexamic acid. The two most commonly documented DOACs were apixaban (n = 1072) and rivaroxaban (n = 716). The most common indication for DOAC use was atrial fibrillation (n = 1874), followed by VTE (n = 239). Of the studies examining hemostatic efficacy, the majority (n = 9, 64.3%) used the ANNEXA-4 criteria for hemostasis, followed by ISTH criteria (n = 3, 21.4%). Fourteen studies reported hemostatic efficacy, with a pooled risk ratio of 1.1 (95% CI 1.03-1.20, p = 0.005, I2 = 18%) favouring Andexanet alfa. Thirteen studies reported thrombotic events, with a pooled risk ratio of 1.22 (95% CI 0.86-1.74, p = 0.26, I2 = 0%). Finally, 13 studies examined mortality, with a pooled risk ratio of 0.81 (95% CI 0.63-1.05, p = 0.26, I2 = 42%). Subgroup analyses comparing Andexanet alfa to 4F-PCC found similar results across hemostatic efficacy and thrombotic complications but noted a significant mortality risk reduction in favour of Andexanet alfa (RR 0.76, 95% CI: 0.58-0.99, p=0.04, I2 = 38%). Heterogeneity was low for both hemostatic efficacy and thrombotic complications and moderate for mortality. Conclusions Our meta-analysis found improved hemostatic efficacy with Andexanet alfa compared to standard-of-care, with no effect on thrombotic complications and mortality rates. This suggests that Andexanet alfa is a favourable treatment option for hemostasis in patients experiencing life-threatening ICH.
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 | 0,011 | 0,022 |
| Méta-épidémiologie (sens strict) | 0,002 | 0,001 |
| Méta-épidémiologie (sens large) | 0,022 | 0,043 |
| Bibliométrie | 0,008 | 0,008 |
| Études des sciences et des technologies | 0,001 | 0,001 |
| Communication savante | 0,003 | 0,002 |
| Science ouverte | 0,002 | 0,002 |
| Intégrité de la recherche | 0,002 | 0,002 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,005 | 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 ».