Direct oral anticoagulants have different gastrointestinal safety profiles

Background

When physicians prescribe anticoagulants, they prefer direct oral anticoagulants (DOACs) in approximately 62% of new cases, because they are at least equivalent to warfarin for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation (AF), and easier to use since there is no need for monitoring [1,2]. Compared with warfarin, there is a 25–30% increased risk of gastrointestinal (GI) bleeding with DOACs, however, the comparative risk of GI bleeding between them is not known [3-6].

In this analysis of a population-based cohort, the GI safety profile of DOACs was assessed in a head-to-head comparison, with focus on the very elderly (≥75 years). In total, 6 542 patients with AF were included in the apixaban vs dabigatran cohort, 6 565 AF patients in the apixaban vs rivaroxaban cohort and 15 787 AF patients in the rivaroxaban vs dabigatran cohort.

Main results

Risk of GI bleeding with rivaroxaban vs dabigatran:

• The overall incidence of GI bleeding events with rivaroxaban was 2.74/100 patient-years and 2.02/100 patient-years with dabigatran.
• A 20% increase in GI bleeding events was observed with rivaroxaban when compared to dabigatran (HR: 1.20; 95% CI: 1.00-1.45).
• Comparing GI bleeding risk on rivaroxaban vs. dabigatran across different age categories revealed an HR of 2.03, 1.44 and 1.06 for patients between 18-64 years, 65-74 years and ≥75 years, respectively.

Risk of GI bleeding with apixaban vs dabigatran:

• The incidence of GI bleedings was 1.38/100 patient-years with apixaban vs 2.73/100 patient-years with dabigatran.
• A 61% reduction in events was observed with apixaban when compared to dabigatran (HR: 0.39; 95% CI: 0.27-0.58).
• With both agents, the incidence rate of GI bleeding increased with advancing age.
• Comparing GI bleeding risk on apixaban vs. dabigatran across different age categories revealed an HR of 0.38, 0.25 and 0.45 for patients between 18-64 years, 65-74 years and ≥75 years, respectively.

Risk of GI bleeding with apixaban vs rivaroxaban:

• The overall incidence rate of GI bleeding events with apixaban was 1.34/100 patient-years, and with rivaroxaban it was 3.54/100 patient-years.
• With apixaban, a 67% reduction in events was observed compared with rivaroxaban (HR: 0.33; 95% CI: 0.22-0.49).
• The incidence rate of GI bleeding events increased with advancing age in both groups.
• Comparing GI bleeding risk on apixaban vs. rivaroxaban across different age categories revealed an HR of 0.38, 0.18 and 0.39 for patients between 18-64 years, 65-74 years and ≥75 years, respectively.

Apixaban had the most favourable GI safety profile compared with rivaroxaban (ARR= -2.20; 95% CI: -3.00 to -1.40; NNH = 45) and dabigatran (ARR = -1.35; 95% CI: -2.03 to -0.67; NNH = 74).

Conclusion

References

Find this article online at Gastroenterology