Does Anticoagulant Choice Affect Fracture Risk in AF?

By Laurie Gelb, MPH, BCPA

The study used claims data of patients prescribed oral anticoagulants from January 1, 2010, through September 30, 2015, with an average followup period of 17 months. To reduce confounding, patients were matched on age, gender, AF-related stroke risk (CHA2DS2-VASc), and high-dimensional propensity scores to further reduce confounding.

The take-home conclusion was caution in using warfarin in AF patients with particular fracture risks.

The final analysis included 167, 275 patients with non-valvular AF who were intially prescribed warfarin or one of three DOACs (dabigatran, rivaroxaban, and apixaban). Groups were categorized according to the first oral anticoagulant they were prescribed: dabigatran (Pradaxa, 18.9%), rivaroxaban (Xarelto, 21.1%), apixaban (Eliquis,10.6%), and warfarin (49.4%).

The sample was 62% male, with an average age of 69. To optimize the power to detect differences between DOACs and warfarin, each DOAC user was matched with up to three warfarin recipients.

Over an average 17 months of followup, the sample experienced 7294 total fractures, 28% requiring hospitalization. Of the fractures requiring hospitalization, 41% were hip fractures.

In multivariable-adjusted, propensity score–matched Cox proportional hazards regression models, relative to new users of warfarin, new users of DOACs tended to be at lower risk of fractures requiring hospitalization (hazard ratio [HR], 0.87; 95% CI, 0.79–0.96) and all clinical fractures (HR, 0.93; 95% CI, 0.88–0.98), but the association with hip fractures was not statistically significant. Unsurprisingly, larger differences were seen in patients with a diagnosis of osteoporosis.

“Vitamin K is important in post-translational glutamination of osteocalcin, the major noncollagenous bone matrix protein. Warfarin interferes with this process and consequently inhibits the activation of bone matrix proteins,” the investigators noted.

They recommended caution when prescribing warfarin to patients with Afib at high risk of fracture, which could potentially include those with osteoporosis and those lacking bone density test results, as well as patients with questionable home environments, known balance issues and/or frailty.

As with any cohort study, looking backward at claims, this study has limitations. Even after matching, the warfarin and apixaban groups were older and had higher CHA2DS2-VASC scores, a concern since variables that contribute to stroke risk could also affect falls and other fracture-causing events.

In addition, since warfarin is generic, it is much more likely to be prescribed to patients for whom cost is an issue, who could be at higher fracture risk due to low adherence with osteoporosis medications, or because of environmental factors, nutrition, etc. Moreover, the study only used insured patients, and edoxaban (Savaysa) was excluded due to low sample size.

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