The relative risk of major gastrointestinal bleeding (GIB) among different direct oral anticoagulants (DOACs) is debatable. Randomized controlled trials (RCTs) comparing DOACs with each other are lacking. We performed network meta-analysis to assess whether the risk of major GIB differs based on type and dose of DOAC. Literature search of PubMed, EMBASE and Cochrane databases from inception to August 2019, limited to English publications, was conducted to identify RCTs comparing DOACs with warfarin or enoxaparin for any indication. Primary outcome of interest was major GIB risk. We used frequentist network meta-analysis through the random-effects model to compare DOACs with each other and DOACs by dose to isolate the impact on major GIB. Twenty-eight RCTs, including 139 587 patients receiving six anticoagulants, were selected. The risk of major GIB for DOACs was equal to warfarin. Comparison of DOACs with each other did not show risk differences. After accounting for dose, rivaroxaban 20 mg, dabigatran 300 mg and edoxaban 60 mg daily had 47, 40 and 22% higher rates of major GIB versus warfarin, respectively. Apixaban 5 mg twice daily had lower major GIB compared to dabigatran 300 mg (OR, 0.63; 95% CI, 0.44-0.88) and rivaroxaban 20 mg (OR, 0.60; 95% CI, 0.43-0.83) daily. Heterogeneity was low, and the model was consistent without publication bias (Egger's test: P = 0.079). All RCTs were high-quality with low risk of bias. DOACs at standard dose, except apixaban, had a higher risk of major GIB compared to warfarin. Apixaban had a lower rate of major GIB compared to dabigatran and rivaroxaban.

BACKGROUND: Current guidelines give class I recommendations for uninterrupted use of dabigatran rivaroxaban as an alternative to vitamin K antagonist (VKA) in patients of atrial fibrillation (AF) who are undergoing catheter ablation. The recent randomized controlled trials have shown similar efficacy of novel oral anticoagulants when compared to VKA in these patients. We sought to perform a meta-analysis with a focus on subgroup analysis of novel oral anticoagulants. METHODS: We searched PubMed, Clinical trials registry and the Cochrane Center Register of Controlled Trials were searched through August 2020. Six RCTs studies (n = 2260) comparing the use of NOACs versus VKA in patients with AF undergoing catheter ablation were included. The odds ratio (OR) with 95% confidence interval was computed and P < 0.05 was considered as a level of significance. Major adverse cardiac events (MACE) were considered as a primary endpoint. RESULTS: Our results showed a significant difference in MACE between NOACs and VKA [OR 0.57 (0.37-0.88); P = 0.01] and in major bleeding events [OR 0.55 (0.35-0.86); P = 0.009], which is mainly derived from the use of dabigatran. No significant difference in MACE or major bleeding events was found on the subgroup analysis of rivaroxaban and apixaban over VKA therapy. CONCLUSION: Uninterrupted use of NOACs is safe and effective alternative for the prevention of cerebral thromboembolism and reducing the risk of major bleeding in patients undergoing catheter ablation of AF. However, the individual subgroup analysis showed that only dabigatran is superior to VKA in terms of reducing MACE through a reduction in major bleeding. The rivaroxaban, apixaban and edoxaban are non-inferior to VKA therapy based on these results. Further studies are needed to generalize these recommendations in morbidly obese patients.