Which oral anticoagulant (OAC) has a lower risk of gastrointestinal (GI) bleeding?

From the Guidelines

Apixaban has the lowest risk of gastrointestinal bleeding among oral anticoagulants. When comparing the direct oral anticoagulants (DOACs), apixaban has consistently demonstrated a more favorable GI bleeding profile than rivaroxaban, dabigatran, and edoxaban 1. The standard dose for apixaban is 5 mg twice daily for most patients, though 2.5 mg twice daily is recommended for patients meeting two of three criteria: age ≥80 years, body weight ≤60 kg, or serum creatinine ≥1.5 mg/dL.

Key Considerations

• Apixaban's reduced GI bleeding risk is likely related to its twice-daily dosing regimen and balanced elimination profile (both renal and hepatic) 1.
• Warfarin, the traditional vitamin K antagonist, typically has a higher GI bleeding risk than apixaban but may be comparable to or lower than some other DOACs depending on how well the INR is controlled 1.
• Patient-specific factors, including renal function, age, weight, concomitant medications, and history of GI bleeding, should be considered when selecting the most appropriate agent 1.
• Dabigatran 110 mg twice daily may also be a suitable option for patients with prior gastrointestinal bleeding, as it is associated with a comparable risk of GI bleeding to warfarin 1.

Evidence Summary

• A 2019 study published in the Journal of Thrombosis and Haemostasis noted that apixaban may be safer with respect to gastrointestinal bleeding risk compared to other DOACs 1.
• A 2018 guideline published in Chest suggested that apixaban or dabigatran 110 mg twice daily may be preferable in patients with prior gastrointestinal bleeding, as they are associated with a lower risk of GI bleeding compared to warfarin 1.
• A 2016 study published in the European Heart Journal found that apixaban had a comparable risk of GI bleeding to warfarin, while dabigatran 150 mg twice daily, rivaroxaban 20 mg once daily, and edoxaban 60 mg once daily had an increased risk of GI bleeding 1.

From the FDA Drug Label

The rate of any gastrointestinal bleeds in patients receiving dabigatran etexilate capsules 150 mg was 3.1% (2.4% on warfarin) in the RE-COVER and RE-COVER II studies. In the RE-MEDY study, the rate of any gastrointestinal bleeds in patients receiving dabigatran etexilate capsules 150 mg was 3.1% (2.2% on warfarin). In the RE-SONATE study, the rate of any gastrointestinal bleeds in patients receiving dabigatran etexilate capsules 150 mg was 0.7% (0.3% on placebo). There was a higher rate of any gastrointestinal bleeds in patients receiving dabigatran etexilate capsules 150 mg than in patients receiving warfarin (6.6% vs 4.2%, respectively) in the RE-LY study.

Comparison of GI Bleeding Risk

• Dabigatran etexilate capsules 150 mg: 3.1% (RE-COVER and RE-COVER II), 3.1% (RE-MEDY), 0.7% (RE-SONATE), 6.6% (RE-LY)
• Warfarin: 2.4% (RE-COVER and RE-COVER II), 2.2% (RE-MEDY), 4.2% (RE-LY)
• Placebo: 0.3% (RE-SONATE)

Based on the available data, warfarin appears to have a lower GI bleeding risk compared to dabigatran etexilate capsules 150 mg in some studies, but the results are not consistent across all studies 2, 2.

From the Research

Oral Anticoagulants and GI Bleeding Risk

• The risk of gastrointestinal bleeding (GIB) is a major concern in patients on oral anticoagulation therapy 3.
• Studies have shown that dabigatran 150 mg twice daily and rivaroxaban 20 mg once daily increase the risk of GIB compared to warfarin 3.
• Apixaban, on the other hand, appears to have no increased risk of GIB compared to warfarin 3.
• A multinational population-based cohort study found that apixaban use was associated with lower risk for GIB than use of dabigatran, edoxaban, or rivaroxaban 4.

Comparison of Oral Anticoagulants

• A systematic review and network meta-analysis found that apixaban 5 mg twice daily had lower major GIB compared to dabigatran 300 mg and rivaroxaban 20 mg daily 5.
• The same study found that rivaroxaban 20 mg, dabigatran 300 mg, and edoxaban 60 mg daily had higher rates of major GIB compared to warfarin 5.
• Another study found that high-dose dabigatran, rivaroxaban, and high-dose edoxaban were associated with a higher risk of GIB compared with warfarin 6.

Prevention and Management of GI Bleeding

• Prevention of NOAC-related GIB includes proper patient selection, using a lower dose of certain NOACs, and correction of modifiable risk factors 6.
• Overt GIB can be managed by withholding NOACs followed by delayed endoscopic treatment, and in severe bleeding, additional measures include administration of activated charcoal and use of specific reversal agents 6.
• A study found that the use of DOAC antagonists, such as idarucizumab for dabigatran and andexanet for rivaroxaban, apixaban, and edoxaban, can be helpful in controlling bleeding in severe and urgent situations 7.