Lower risk of osteoporotic fractures in AF patients with DOAC vs. VKA treatment
In a Danish cohort study of nonvalvular AF patients, DOAC use was associated with a lower risk of osteoporotic fractures compared to VKA treatment.
Osteoporotic Fractures in Patients With Atrial Fibrillation Treated With Conventional Versus Direct AnticoagulantsLiterature - Binding C, Bjerring Olesen J, Abrahamsen B, et al. - J Am Coll Cardiol 2019;74:2150–8, doi.org/10.1016/j.jacc.2019.08.1025
Introduction and methods
An increased risk of fractures in patients taking oral anticoagulants has been suggested by several studies [1-3]. Explanations might be found in an association between warfarin and undercarboxylated osteocalcin, which is associated with low bone mineral density (BMD) [4-6], and dietary restrictions that come with VKA prescription, contributing to a low BMD. There is limited evidence on differences between VKAs and DOACs on osteoporotic fractures. Therefore, this study examined risk of osteoporotic fractures in AF patients taking DOAC or VKA therapy.
For this purpose, data from Danish registries were used and linked. Study period was between Jan 1, 2013 and June 30, 2017. All Danish patients with nonvalvular AF were identified who were first-time users of VKA, or DOAC dabigatran, rivaroxaban, apixaban or edoxaban. One of inclusion criteria was 180 days of OAC use and an exclusion criterium was use of osteoporotic medication. Five outcomes were studied: any fracture, major osteoporotic fracture, hip fracture, initiation of osteoporosis medication, and composite endpoint of any fracture of initiation of osteoporosis medication. Baseline was 180 days after filling first prescription of VKA or DOAC and follow-up was two years. A total of 37350 patients were included; 12168 (32.6%) took a VKA, 25182 (67.4%) a DOAC.
Main results
- 2-year absolute standardized risk of major osteoporotic fractures was 2.82% (95% CI: 2.46% to 3.19%) for VKA-treated patients and 2.29% (95% CI: 2.02% to 2.49%) for DOAC-treated patients (HR: 0.85; 95% CI: 0.72 to 0.99).
- There was no difference in the 2-year risk of hip fracture between the two groups; 1.65% (1.38% to 1.92%) in the VKA group vs. 1.40% (1.24% to 1.56%) in the DOAC group (HR: 0.91, 95%CI: 0.74-1.13).
- 2-year risk of any fracture was 3.77% (95% CI: 3.37% to 4.19%) for VKA treated patients and 3.09% (95% CI: 2.85% to 3.33%) for DOAC treated patients (HR: 0.85; 95% CI: 0.74 to 0.97).
- VKA-treated patients were found to have a 3.14% (95% CI: 2.79% to 3.51%) absolute standardized 2-year risk of starting osteoporosis medication, whereas DOAC-treated patients had a 2-year absolute standardized risk of 2.44% (95% CI: 2.22% to 2.66%) (HR: 0.82; 95% CI: 0.71 to 0.95).
- For the combined endpoint of any fractures and initiation of osteoporotic medication, VKA-treated patients had an absolute standardized 2-year risk of 6.43% (95% CI: 5.89% to 6.94), and DOAC-treated patients 5.21% (95% CI: 4.90% to 5.52%) (HR: 0.84; 95% CI: 0.76 to 0.93).
Conclusion
An analysis of data from Danish AF patients showed that DOAC therapy was associated with a lower risk of major osteoporotic fractures, any fractures, starting osteoporosis medication, and a combined endpoint of any fractures and initiation of osteoporotic medication compared to VKA treatment. These findings suggest that DOAC use could be preferred over VKA treatment in AF patients with risk factors for osteoporotic fractures.
References
1. Gage BF, Birman-Deych E, Radford MJ, et al. Risk of osteoporotic fracture in elderly patients taking warfarin: results from the National Registry of Atrial Fibrillation 2. Arch Intern Med 2006;166:241–6.
2. Rejnmark L, Vestergaard P, Mosekilde L. Fracture risk in users of oral anticoagulants: a nationwide case-control study. Int J Cardiol 2007;118:338–44.
3. Caraballo PJ, Heit JA, Atkinson EJ, et al. Longterm use of oral anticoagulants and the risk of fracture. Arch Intern Med 1999;159:1750–6.
4. Namba S, Yamaoka-Tojo M, Hashikata T, et al. Long-term warfarin therapy and biomarkers for osteoporosis and atherosclerosis. BBA Clin 2015;4:76–80.
5. Namba S, Yamaoka-Tojo M, Kakizaki R, et al. Effects on bone metabolism markers and arterial stiffness by switching to rivaroxaban from warfarin in patients with atrial fibrillation. Heart Vessels 2017;32:977–82.
6. Barnes C, Newall F, Ignjatovic V, et al. Reduced bone density in children on long-term warfarin. Pediatr Res 2005;57:578–81.