Warfarin may worsen OA progression due to VKA effect: study

Thursday, 29 Apr 2021

Warfarin’s vitamin K antagonism may have detrimental effects on joint tissues that could contribute to progression of osteoarthritis, new research suggests.

In patients with osteoarthritis receiving anticoagulation for atrial fibrillation, warfarin use was associated with an increased risk of knee and hip replacement – a marker for later stage OA – compared to treatment with a DOAC, a study has found.

Warfarin’s inhibition of vitamin K likely led to inadequate functioning of Gla proteins, which play a role both in blood coagulation and in bone and cartilage, wrote study authors led by Dr Priyanka Ballal, of Boston University School of Medicine, in Annals of the Rheumatic Diseases.

To investigate warfarin’s connection to joint replacement as a reflection of end-stage OA, researchers used a nested case-control design based on patient data derived from a UK primary care electronic records database.

They included a total of 857 patients with either knee or hip replacement, of whom 64.6% were warfarin users for AF and the remaining 35.4% were DOAC users, and compared these to 3,428 matched controls, of whom 56.1% were warfarin users and 43.9% were DOAC users.

Warfarin use was associated with a 59% higher risk of having a knee or hip replacement than DOAC use (adjusted odds ratio 1.59 [95% CI, 1.31-1.92]). Longer duration of warfarin use was associated with higher risk, at 86% for those with at least four years of use compared with those using warfarin for less than one year. Results were similar when divided by type of joint replacement.

The authors recognised that an observational study such as this could not offer a definitive causal link between warfarin and joint replacement, but they noted that a randomised trial comparing anticoagulants for an OA endpoint is unlikely to be performed.

Along with warfarin’s effect on vitamin K and Gla proteins, the anticoagulant could also have direct effects on inflammation, they suggested.

“Given the worldwide prevalence and impact of OA and lack of effective disease-modifying therapies, our study supports the need for a well-powered randomised control trial evaluating vitamin K supplementation in OA,” the authors wrote.

“Our study also raises the consideration of preferentially using DOACs rather than warfarin, when appropriately indicated, in people with OA”

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