Efficacy and Safety of Direct Oral Anticoagulants: A Systematic Review of Population Based Studies
Notice bibliographique
Résumé
Abstract Background.Safety and efficacy of direct oral anticoagulants (DOACS) has been established in randomized trials but an increasing number of "real world" data outside clinical trials has become available after approval. In this study we aimed to assess the efficacy and safety of DOACS in population-based studies in the context of non-valvular atrial fibrillation (NVAF), thromboprophylaxis in orthopedic surgery (OS), and treatment of acute venous thromboembolism (VTE). Methods.We conducted a systematic review of observational studies assessing the safety and efficacy of DOACs (including dabigatran, rivaroxaban and apixaban) in patients with NVAF, OS and VTE treatment. Efficacy outcomes included stroke (NVAF studies) and VTE (OS studies). Safety outcomes included major bleeding (MB) (as defined by investigators), gastrointestinal (GI) and central nervous system (CNS) bleeding. If feasible we conducted a meta-analysis of incidence rates (IR) and proportions using both fixed and random effects models. Results.Of 84 potentially relevant studies we included36 full text articles published between 2012 and 2016. Three groups of studies were identified: NVAF (22 studies), thromboprophylaxis in OS (10 studies), and miscellaneous (4 studies).Of the miscellaneous studies, only 1 study assessed DOACS in the treatment of acute VTE. Studies assessing NVAF. The 22 studies included 158,554 patients of which, 70,608 were evaluable for stroke, 80,810 for MB, 88,397 for CNS bleed, and 97,738 for GI bleed. Overall, the percent of patients developing stroke, MB, CNS and GI bleed were similar with both random and fixed models (Table 1). Among NVAF patients, a meta-analysis of studies with follow up information (7 studies, n=40,955) showed that the IR of stroke for all DOACS was 1.8 [95%CI: 1.72-1.98] and 2.3 [95%CI: 1.99-2.61] per 100 person - year (100 PY) for the fixed and random estimates, respectively, regardless of previous vitamin K antagonist (VKA) exposure. The IR of CNS bleeding with dabigatran was 0.6 [95%CI: 0.54-0.72] and 1.3 [95%CI: 0.13-2.47] per 100 PY for fixed and random estimates, respectively. The IR of bleeding-related deaths in NVAF with all DOACS was 0.1 [95%CI: 0.07-0.17] per 100 PY (fixed) and 0.2 [95%CI: 0-0.8] per 100 PY (random). Sensitivity analyses showed that in VKA naïve patients, dabigatran at 110 mg bid (D110) carried a significantly higher risk of stroke than dabigatran 150 mg bid (D150) [RR: 3.4; 95%CI: 2.57-4.50; p<0.0001], whereas in VKA experienced patients the risk of stroke with D110 was similar to D150 [RR: 2.0; 95%CI: 0.76-5.28; p=0.15]. In dabigatran users, VKA naïve patients carried around a 2-fold significant increase in the risk of major bleeding (MB) compared to previous VKA users [RR: 1.8; 95%CI: 1.05-3.12; p=0.03]. While the proportion of CNS bleeding was extremely low with all doses of all DOACS, the risk of GI bleed with D150 was statistically significantly higher than that of D110 in both populations of VKA naïve [RR:1.6; 95%CI: 1.14-2.31; P=0.006], and VKA experienced dabigatran users [RR: 8.3; 95% CI: 3.39-20.46; p<0.0001]. Studies in OS. Studies assessing DOACs in patients undergoing orthopedic surgery (n=27,158) showed a VTE rate of 0.8% [95%CI: 0.73-0.95] (fixed) and 1.5% [95%CI: 1.8-1.11] with (random). The MB rate was 0.7% [95%CI: 0.61-0.81] (fixed) and 2.2% [95%CI: 2.61-1.79] (random). Conclusion.DOACS used in NVAF and orthopedic surgery are effective and safe in real-world studies as in RCTs. However, in NVAF, dabigatran dose and previous exposure to VKA seem to impact the risks of stroke, MB, and GI bleed. CNS bleed rates were consistently low with all DOACS at all doses, whether in VKA naïve or VKA experienced populations. Data for apixaban and VTE treatment is currently limited. Disclosures Lazo-Langner: Pfizer: Honoraria; Daiichi Sankyo: Research Funding; Bayer: Honoraria.
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 | 0,015 | 0,058 |
| Méta-épidémiologie (sens strict) | 0,002 | 0,001 |
| Méta-épidémiologie (sens large) | 0,010 | 0,013 |
| Bibliométrie | 0,011 | 0,013 |
| Études des sciences et des technologies | 0,001 | 0,001 |
| Communication savante | 0,003 | 0,002 |
| Science ouverte | 0,002 | 0,001 |
| Intégrité de la recherche | 0,001 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,003 | 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 ».