Warfarin Use Significantly Increases the Risk of THA or TKA in Patients with OA, Study Finds

    Patients with osteoarthritis (OA) who are prescribed warfarin (Coumadin) to treat atrial fibrillation are more likely to progress to total hip arthroplasty (THA) or total knee arthroplasty (TKA) than patients who take direct oral anticoagulants, according to research presented during ACR Convergence 2020, the annual meeting of the American College of Rheumatology

    Vitamin K deficiency has been associated with OA, and recent research has shown that vitamin K supplementation may reduce OA progression. However, no studies to date have evaluated whether vitamin K antagonism with the use of warfarin can be detrimental to OA. The new study reported at ACR Convergence 2020 evaluated the relationship of warfarin to the risk of THA or TKA in patients with end-stage OA.

    “We hypothesized that disruption of the functioning of vitamin K-dependent bone and cartilage proteins through vitamin K antagonism may lead to abnormalities in chondrocyte functioning, with adverse effects on cartilage health, which in turn can increase the risk of developing or worsening of OA,” said study co-author Priyanka Ballal, MD, a rheumatology fellow at Boston University Medical Center.

    “Because direct oral anticoagulants are alternate options for anticoagulation that do not inhibit vitamin K’s functioning, clarifying this risk [with] warfarin would give providers and patients valuable information when they consider their choice of anticoagulation in patients with atrial fibrillation.” 

    The nested, case-control study used data from the Health Improvement Network, a general practitioner-based electronic medical records database from the UK that is representative of the general population. The study sample was limited to adults ages 40 to 89 diagnosed with atrial fibrillation, which warrants anticoagulation therapy.

    The researchers compared patients who were taking warfarin with patients taking direct oral anticoagulants, which do not inhibit vitamin K and were first marketed in the UK in 2008. They excluded patients:

    • Who had undergone THA or TKA before 2014
    • Who had severe comorbidities that would limit their ability to undergo surgery
    • Who took warfarin or direct oral anticoagulants within 1 year prior to the study period
    • Who used both drugs during the study period

    They identified “cases” as any patient who had THA or TKA between 2014 and 2018, with the surgery date being the index date for cases. Each case was matched with up to 4 controls for age and gender. Warfarin and direct oral anticoagulant use were defined as having 1 or more prescription after the study entry and within 1 year before the index date. 

    The study included 913 patients who had either THA or TKA and 3652 controls. Mean age was 74, and 46% of study participants were female. Of the 913 surgery cases, 64.9% were warfarin users and 35.1% were direct oral anticoagulant users. 

    After adjusting for potential confounders, the researchers found that warfarin users had 1.57 times higher odds of undergoing THA or TKA than direct oral anticoagulant users. They also found an increasing risk of requiring THA or TKA with the duration of warfarin use compared with direct oral anticoagulants use. 

    The researchers stressed that their data supports the importance of adequate vitamin K in limiting the progression of OA in patients and raises the consideration of using direct oral anticoagulants instead of warfarin when indicated in individuals with OA or at risk for developing OA.

    “Given these potential adverse effects of warfarin on joint health, our study suggests that direct oral anticoagulants could be considered for managing atrial fibrillation among patients who have OA,” Dr. Ballal said. “The next steps for our group’s research are the design and launch of an adequately powered randomized trial to test the efficacy of vitamin K supplementation for OA outcomes.”


    Ballal P, Peloquin C, Boer C, Neogi T. Warfarin Use and Risk of Knee and Hip Replacements. Abstract 0934. Presented at the ACR Convergence 2020, November 5-9, a virtual meeting.