Warfarin Linked to Greater Hip or Knee Replacement Needs

Priyanka Ballal, MD

Hip or knee replacement among persons is 57% more likely among those taking warfarin than those taking anticoagulants for atrial fibrillation, according to new data.

In a new study presented at the American College of Rheumatology (ACR) Convergence 2020, an international team of investigators reported findings suggesting the vitamin K antagonist therapy is significantly associated with knee and/or hip replacement needs. Such indications would potentially support the need for adequate vitamin K levels in patients with osteoarthritis.

Led by Priyanka Ballal, MD, Rheumatology Fellow at Boston University Medical Center, investigators sought to interpret the association of warfarin to risks for knee and hip replacements—a marker of end-stage osteoarthritis—in part due to suggesting yet limited evidence.

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

Their nested case-control assessment gauged The Health Improvement Network, an electronic medical records database for UK-based general practitioners representative of the general population. Their study sample included adults aged 40-89 with diagnosed atrial fibrillation, as such a condition warrants anticoagulation therapy such as warfarin.

In this population, they compared warfarin with direct oral anticoagulants (DOACs), which provide benefit for atrial fibrillation without antagonizing vitamin K.

“Because DOACs were first marketed in the UK in 2008, we limited our study to those who had been enrolled for ≥1 year with a (general practitioner) between 2009-2018,” investigators wrote. “We excluded individuals with knee or hip replacement prior to 2014, severe co-morbidities that would limit surgery, those with warfarin or DOAC use within 1 year prior to our study period, and those who used both drugs during study period.”

Cases of either hip or knee replacement were identified between 2014-2018—with the index date being the day of surgery—and matched with up to 4 controls by age and gender. Ballal and colleagues defined warfarin and DOAC use as at least 1 prescription post-study entry and within 1 year prior to the index rate.

Their assessment included 913 subjects with hip or knee replacements, age- and gender-matched 4:1 with 3652 total controls, of which mean patient age was 74 years old and gender was 46% female.

Nearly two-thirds (64.9%) of replacement-care patients used warfarin, while 35.1% used DOACs. Among controls, 56.3% used warfarin while 43.6% used DOACs.

Warfarin users reported an adjusted 1.57 odds ratio (OR) for hip or knee replacement versus DOAC users (95% CI, 1.30-1.89). Investigators also observed an increasing risk of hip or knee replacement risk with regard to duration of warfarin exposure versus DOACs.

“Our research supports the importance of adequate Vitamin K and dependent proteins for limiting progression of OA,” Ballal said. “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.”

In discussing next steps for assessment, Ballal suggested the launch of an adequately-powered randomized trial which would assess the actual efficacy of vitamin K supplementation for osteoarthritis outcomes.

The study, “Warfarin Use and Risk of Knee and Hip Replacements,” was presented at ACR 2020.