Direct oral anticoagulants versus warfarin in nonvalvular atrial fibrillation patients with prior gastrointestinal bleeding: a network meta-analysis of real-world data

Purpose The objective of present study was to compare the safety and efficacy of resuming direct-acting oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) in patients with atrial fibrillation (AF) and prior gastrointestinal bleeding (GIB). Methods PubMed, Embase, Web of Science, and the Cochrane Library were searched from their inception until 2 June 2021 for observational cohort studies in patients with AF, who resumed VKAs or DOACs after a history of GIB. Studies that reported data on clinical outcomes including risk of recurrent GIB, thromboembolic events, or all-cause mortality were included. A network meta-analysis was performed to calculate the pooled hazard ratio (HR) and associated 95% credible intervals (CIs), using a random effects model in a Bayesian framework. Results A total of 10 studies were included in the final analysis, including 59,244 AF patients with prior GIB, of whom 27,793 resumed DOACs, 24,635 resumed warfarin, and 6816 did not resume anticoagulation. Compared with no resumption of anticoagulation, resumption of warfarin was associated with an increased risk of recurrent GIB (HR 1.33, 95% CI: 1.06-1.70), but no increased risk of recurrent GIB was found with resumption of DOACs (HR 1.22, 95% CI: 0.88-1.71); among individual DOACs, only rivaroxaban was associated with an increased risk of recurrent GIB (HR 1.67, 95% CI: 1.16-2.65). Compared with no resumption of anticoagulation, resumption of DOACs and warfarin was associated with a significant reduction in all-cause mortality (HR 0.57, 95% CI: 0.40-0.84; HR 0.58, 95% CI: 0.44-0.79), but no statistically significant reduction in thromboembolic events (HR 0.69, 95% CI: 0.4-1.2; HR 0.83, 95% CI: 0.55-1.29). Conclusions In AF patients with prior GIB, resumption of DOACs may be safer, except for rivaroxaban.