Key result
Apixaban cuts major GI bleeding risk ~37% versus dabigatran and rivaroxaban.
Why the study?
The relative risk of major gastrointestinal bleeding among different DOACs is debatable, and randomized controlled trials comparing DOACs directly are lacking.
Does the type and dose of direct oral anticoagulants affect the risk of major gastrointestinal bleeding compared to warfarin or other DOACs?
Meta-Analysis (n=139,587)
Does the type and dose of direct oral anticoagulants affect the risk of major gastrointestinal bleeding compared to warfarin or other DOACs?
Standard doses of DOACs, with the exception of apixaban, are associated with a higher risk of major gastrointestinal bleeding compared to warfarin, and apixaban has a lower risk compared to dabigatran and rivaroxaban.
Apixaban may be preferred over other DOACs to lower major GI bleeding risk; extends comparative safety evidence guiding agent selection.
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.
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Radadiya et al. (2021) conducted a meta-analysis in Any indication requiring anticoagulation (n=139,587). Direct oral anticoagulants (DOACs) vs. Warfarin or enoxaparin was evaluated on Major gastrointestinal bleeding (GIB) risk (OR 0.63, 95% CI 0.44-0.88). Apixaban 5 mg twice daily had a lower risk of major gastrointestinal bleeding 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).
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