All DOACs appeared to lower risk in population-based study

Patients with atrial fibrillation have a lower risk of osteoporotic fracture when they are treated with direct oral anticoagulants (DOACs) compared to treatment with warfarin, researchers found.

However, their population-based cohort study did not find any changes in risk depending on the kind of DOAC (apixaban, dabigatran, or rivaroxaban) used.

The study, led by Wallis C.Y. Lau, PhD, UCL School of Pharmacy, London, United Kingdom, and Centre for Safe Medication and Practice Research, The University of Hong Kong, Hong Kong, China, was published in the Annals of Internal Medicine.

Osteoporosis is a major cause of morbidity and mortality, and according to a study in the Journal of Bone and Mineral Research, accounts for approximately 2 million fractures, and contributes to 65,000 deaths annually in the United States.

According to Lau and colleagues, while it has been suggested that the use of warfarin to treat atrial fibrillation increases the risk of osteoporotic fracture, most studies examining the link between warfarin and fractures are not recent and resulted in inconsistent findings.

DOACs such as apixaban, dabigatran, or rivaroxaban have recently been introduced as alternatives to warfarin, and a recent meta-analysis of randomized controlled trials of DOACs found fewer reports of fractures with DOACs compared to warfarin.

These trials, however, weren’t designed to evaluate fracture risks in clinical practice, Lau and colleagues pointed out, adding that population-based studies are needed to help determine the risk for osteoporotic fracture for different oral anticoagulants.

“Given that oral anticoagulants are often prescribed to older adults who have multiple risk factors for osteoporotic fractures, further clarity on their role in fracture risk is needed,” Lau and colleagues suggested. “This is particularly relevant to persons with Afib, who were reported to have a higher incidence of hip fractures than those without Afib.”

Therefore, they performed a population-based cohort study to examine whether apixaban, dabigatran, or rivaroxaban are associated with a lower risk of fracture compared to warfarin in patients with atrial fibrillation.

For purposes of this study the authors used the electronic health record database of the Hong Kong Hospital Authority to identify patients newly diagnosed with atrial fibrillation between 2010 and 2017. Of the 23,515 patients identified there were 3,241 apixaban users, 6,867 dabigatran users, 3,866 rivaroxaban users, and 9,541 warfarin users. The overall mean age of the study population was 74.4 years and ranged from 73.1 years in the warfarin cohort to 77.9 years in the apixaban group.

Patients were followed until the occurrence of the study outcome, a discontinuation of treatment, a switch to another oral anticoagulant (apixaban, dabigatran, rivaroxaban, warfarin, or edoxaban), or the end of the study period (December 2018), whichever came first.

The primary outcome of the study was the incidence of hip and vertebral fractures. Lau and colleagues found that after a median follow-up of 423 days, patients in the study had experienced 401 fractures — 53 among apixaban patients, 95 dabigatran, 57 rivaroxaban, and 196 warfarin.

At 24 months, the adjusted cumulative incidence of osteoporotic fractures was lower with DOAC use than with warfarin use with propensity score–weighted cumulative incidence differences (CIDs) of:

  • 0.88% [95% CI, 1.66%-0.21%] for apixaban versus warfarin.
  • 0.81% [CI, 1.34%-0.23%] for dabigatran versus warfarin.
  • 1.13% [CI, 1.67%-0.53%] for rivaroxaban versus warfarin.

As for the risk of osteoporotic fracture among the DOACs, the authors reported there were no statistically significant differences seen in all head-to-head comparisons between DOACs at 24 months, with CIDs of 0.6% for apixaban versus dabigatran, 0.25% for rivaroxaban versus apixaban, and 0.32% for rivaroxaban versus dabigatran.

Lau and colleagues suggested this study has important implications considering that prevention of fracture is a key aspect of managing atrial fibrillation patients. “Given the supportive evidence from experimental settings, findings from our study using clinical data, and the indirect evidence provided by the previous meta-analysis of randomized controlled trials, there exists a compelling case for evaluating whether the risk for osteoporotic fractures should be considered at the point of prescribing an oral anticoagulant to minimize fracture risk,” they wrote.

  1. Patients with atrial fibrillation treated with direct oral anticoagulants (DOACs) have a lower risk of osteoporotic fractures compared to patients on warfarin.

  2. There is no statistically significant difference in fracture risk among different DOACs.

Michael Bassett, Contributing Writer, BreakingMED™

Lau has nothing to disclose.

Cat ID: 2

Topic ID: 74,2,438,730,2,913,192,925