Compared with direct oral anticoagulants (DOACs), vitamin K antagonist warfarin was found to be associated with a greater risk for knee and hip replacements, according to study results published in Annals of the Rheumatic Diseases. Study authors also suggested vitamin K antagonism may be detrimental to osteoarthritis (OA).

To determine the association between warfarin use and the risk for knee and hip replacements, the researchers conducted a nested case-control study using an electronic medical database in the UK. Knee or hip replacement cases were identified among adults with atrial fibrillation who were newly prescribed either warfarin or DOACs. Patients were age- and sex-matched with 4 control participants. Conditional logistic regression was used to assess the association between warfarin vs DOAC use and risk for joint replacement.

A total of 857 patients with hip or knee replacements were included in the study, of whom 554 (64.6%) were warfarin users and the remaining 303 (35.4%) were DOAC users. Patients were matched with 3428 control participants, of whom 1923 (56.1%) were warfarin users and 1505 (43.9%) were DOAC users. Mean age of both groups was 75 years; 47% of participants were women.

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Study results showed a 59% higher risk for knee or hip replacement associated with warfarin use compared with DOAC use (adjusted OR 1.59; 95% CI 1.31-1.92). Durations of warfarin use of more than 1 year vs less than 1 year were associated with higher risks. Compared with patients who received warfarin for less than 1 year, those who received warfarin for at least 4 years had an 86% higher risk for knee or hip replacement (95% CI, 1.35-2.57). Results were similar after matching for general practitioner practice and stratifying by joint replacement type.

Study limitations included the observational nature of the study and the potential for residual confounding. In addition, warfarin use was identified by prescription, which may not reflect actual use and adherence. Joint replacements may have also been performed for reasons other than OA.

According to the researchers, these results provided evidence for the detrimental effect of warfarin in OA. They noted, “Given the worldwide prevalence and impact of OA and lack of effective disease-modifying therapies, our study supports the need for a well-powered randomized control trial evaluating vitamin K supplementation in OA.”


Ballal P, Peloquin C, Boer CG, Neogi T. Warfarin use and risk of knee and hip replacements. Ann Rheum Dis. 2021;80:605-609.