Direct oral anticoagulants have different gastrointestinal safety profiles
Gastrointestinal Safety of Direct Oral Anticoagulants: A Large Population-Based Study
Literature - Abraham NS, Noseworthy PA, Yao X, et al. - Gastroenterology 2017;152:1014–1022Background
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
In a large population-based cohort of patients on DOACs due to non-valvular AF, apixaban had the most favourable GI safety profile among all age groups and rivaroxaban had the least favourable profile. These results may facilitate clinical decision making, when it comes to the selection of a DOAC for AF patients.
References
1. Husted S, Lip GY, De CR. Recommendation on the nomenclature for oral anticoagulants: communication from the SSC of the ISTH: comment. J Thromb Haemost 2015;13:2130–2132.
2. Desai NR, Krumme AA, Schneeweiss S, et al. Patterns of initiation of oral anticoagulants in patients with atrial fibrillation- quality and cost implications. Am J Med 2014;127:1075–1082.
3. Abraham NS, Singh S, Alexander GC, et al. Comparative risk of gastrointestinal bleeding with dabigatran, rivaroxaban, and warfarin: population based cohort study. BMJ 2015;350:h1857.
4. Holster IL, Valkhoff VE, Kuipers EJ, et al. New oral anticoagulants increase risk for gastrointestinal bleeding: a systematic review and meta-analysis. Gastroenterology 2013;145:105–112.
5. Ruff CT, Giugliano RP, Braunwald E, et al. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a metaanalysis of randomised trials. Lancet 2014;383:955–962.
6. Which oral anticoagullant for atrial fibrillation? JAMA 2016;315:2117–2118.
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