Vitamin K Antagonist Anticoagulants Increase Knee and Hip Osteoarthritis Incidence and Progression Risk

wafarin, anticoagulant, blood thinner
Warfarin (generic name for type of blood thinner) is an anticoagulant used to prevent the formation of blood clots in the blood vessels and their migration elsewhere in the body. Warfarin is commonly prescribed for treatment of atrial fibrillation, deep venous thrombosis, and pulmonary embolism.
Using the Rotterdam study, researchers examined the effect of vitamin K antagonist anticoagulants, specifically acenocoumarol, on the incidence and progression of hip and knee osteoarthritis.

Vitamin K antagonist anticoagulants (VKAs) increase the risk of incidence and progression of knee and hip osteoarthritis (OA), according to study results published in Annals of the Rheumatic Diseases.

VKAs, including warfarin and acenocoumarol, are responsible for anticoagulation by the inhibition of vitamin K-dependent proteins, and affect the functioning of other vitamin K-dependent proteins, such as matrix Gla protein.

Using data from a cohort of participants in the Rotterdam study, the researchers investigated the effect of acenocoumarol usage on progression and incidence of radiographic OA, as well as the effect of the single-nucleotide variants MGP and VKORC1.

Overall, 3494 patients were included in the analysis. At baseline, there were 363 patients with OA: 75 with hip OA and 288 with knee OA. During the follow-up period, 239 new users of acenocoumarol were identified.

Acenocoumarol users vs nonusers had a greater than 2-fold higher risk (odds ratio [OR], 2.50; 95% CI, 1.94-3.20) for overall OA incidence and progression. Acenocoumarol users also had an increased risk when considering knee (OR, 2.34; 95% CI, 1.69-3.22) and hip joints separately (OR, 2.74; 95% CI, 1.82-4.11). Acenocoumarol users who were carriers of the VKORC1 BB-haplotype and the MGP risk allele (rs1800801-T) had a 4-fold increased risk for OA incidence and progression (OR, 4.18; 95% CI, 2.69-6.50). On the other hand, acenocoumarol users who were carriers of the VKORC1 AA/AB-haplotype, but not the MGP risk allele, did not have a significantly increased risk for overall OA progression and incidence (OR, 1.72; 95% CI, 0.93-3.19)

Study limitations included the relatively low number of acenocoumarol users, generalizability beyond the Central European ancestry-based cohorts, the potential shared disease pathology between OA and VKA indications, the potential health and survivor bias, and residual confounding.

Researchers concluded, “The findings suggest the consideration of novel (or direct) oral anticoagulants in [favor] of VKAs, such as acenocoumarol and warfarin, in people with OA.”


Boer CG, Szilagyi I, Nguyen NL, et al. Vitamin K antagonist anticoagulant usage is associated with increased incidence and progression of osteoarthritis. Ann Rheum Dis. 2021;80(5):598-604. doi:10.1136/annrheumdis-2020-219483