Real-world safety and efficacy of direct oral anticoagulants in atrial fibrillation. a network metanalysis on 605,771 patients

AIMS: To analyse the safety and efficacy of direct oral anticoagulants (DOACs) in real-world studies including atrial fibrillation (AF) patients.METHODS AND RESULTS: Systematic review and meta-analysis of observational studies including AF patients on DOACs. Primary endpoints: any, major, gastrointestinal (GI), intracranial (ICH) and haemorrhagic stroke (HS). Secondary endpoints: ischaemic stroke (IS), Systemic embolism (SE), myocardial infarction (MI) and all-cause of death. A set of pair-wise meta-analyses using a random effect model and a random effect network meta-analysis under a Bayesian framework were performed. Prospero registration number: CRD42019137111. We included 21 studies with 605,771AF patients. Apixaban was associated with lower major and GI bleeding compared with Rivaroxaban (HR 2.0, 95% CI 1.6-2.5) and Dabigatran (HR 1.6, 95% CI 1.3-2.1). The latter drug performed better than Rivaroxaban (HR 1.2, 95% CI 1.0-1.5). Dabigatran and Apixaban had a similar association with HS, but Apixaban performed better than Rivaroxaban (HR 1.8, 95%CI 1.1-3.0). Apixaban had a similar association with Rivaroxaban and Dabigatran for ICH, the latter drug performing better than Rivaroxaban (HR 1.3, 95%CI 1.0-1.7). Rankograms showed that Apixaban was likely to be the first-choice treatment in relation to any (65%) major (100%) and GI bleeding (100%) followed by Dabigatran (46%, 100%, 99%, respectively). Dabigatran and Apixaban had similar rank as first choice for ICH (44% and 55%) and HS (52% and 48%). DOACs showed similar association with IS/SE, MI, all-cause of death.CONCLUSIONS: Analysis of real-world studies shows significant differences for safety among DOACs.