Warfarin Use Linked With Increased Risk of Knee and Hip Replacement in People With Osteoarthritis, Data Suggests
A new study found that warfarin (Coumadin), a medication that is commonly prescribed for atrial fibrillation, is associated with a significantly greater risk of knee and hip replacements in people with osteoarthritis (OA). The research is to be presented on Saturday, November 7, 2020, at the ACR Convergence, the American College of Rheumatology’s annual meeting. Osteoarthritis is the most common form of arthritis and involves the entire joint, including the cartilage, joint lining, ligaments, and bone. It’s usually found in the hands, hips, and knees, according to the Centers for Disease Control and Prevention (CDC). If medications, physical therapy, and lifestyle changes aren’t effective, OA can require joint replacement. RELATED: What Does Arthritis Pain Feel Like?
Vitamin K and Osteoarthritis Progression: What’s the Connection?
Investigators hypothesized that there could be a relationship between taking warfarin and the progression of OA because of the medication’s impact on vitamin K. Vitamin K deficiency has been associated with OA, and there is evidence that vitamin K supplementation may have a protective role in OA, according to research published in March 2016 in Current Nutrition Reports. Warfarin prevents blood clots by inhibiting activation of vitamin K dependent proteins in the blood, according to study coauthor Priyanka Ballal, MD, Rheumatology Fellow at Boston University Medical Center. Based on earlier research, investigators hypothesized that the way warfarin works could impact cartilage functioning, which in turn could increase the risk of developing or worsening of OA.
There’s an Increased Risk of Knee or Hip Replacement With Warfarin, Study Suggests
“Because direct oral anticoagulants (DOACs) are alternate options for anticoagulation that do not inhibit vitamin K’s functioning, clarifying this risk of warfarin would provide providers and patients with valuable data to consider their choice of anticoagulation in patients with atrial fibrillation,” Dr. Ballal wrote in an email message. Examples of DOACs are Pradaxa (dabigatran), Xarelto (rivaroxaban), Eliquis (apixaban), Savaysa (edoxaban), and Bevyxxa (betrixaban). A total of 913 people with knee or hip replacement were matched with 3,652 controls according to age and gender. The average age of participants was 74, 54 percent were men, and all the subjects had a diagnosis of atrial fibrillation. Researchers compared people who were taking warfarin with those taking DOACs; of the 913 surgery cases, 64.9 percent were on warfarin and 35.1 percent were on DOACs. After controlling for body mass index (BMI), existing health conditions, and medications, warfarin users had a 1.57 higher odds of knee replacement or hip replacement than the people on a DOAC. After further accounting for the variation in how osteoarthritis is managed by different health systems, the odds of a warfarin user having replacement surgery was 1.25 times more likely, which was still a significant association, according to the authors. The association increased with longer use of the medications. RELATED: 12 Natural Pain Relief Tips for Knee Osteoarthritis
Many People Live With Osteoarthritis or Atrial Fibrillation
“These results are important because both OA and atrial fibrillation are extremely common diseases. To date, unlike other types of arthritis, we do not have any disease-modifying treatments for OA, with joint replacement reserved for end stage disease,” wrote Ballal. In light of that, it’s very important to optimize the care of patients with OA and ensure that they are not on therapies that are worsening their OA, she added.
People With OA Who Are Managing Afib With Warfarin May Want to Talk to Their Doctor
This research supports the importance of adequate vitamin K and dependent proteins for limiting progression of OA, according to Ballal. “Given these potential adverse effects of warfarin on joint health, our study suggests that DOACs could be considered for managing atrial fibrillation among patients that have OA.” If a patient has both atrial fibrillation managed with warfarin and OA and worsening joint pain, this could warrant a discussion between the patient’s rheumatologist and cardiologist or primary care doctor to consider switching therapy to a DOAC, stated Ballal.
What to Know if You Have Osteoarthritis, Need a Blood Thinner Like Warfarin
“If you have to be put on a blood thinner, then your doctor should probably know if you have significant osteoarthritis of the hip or knee,” agrees Stanford Shoor, MD, researcher and rheumatologist at Stanford Health Care in Palo Alto, California, who was not involved in the study. “Keep in mind that this research isn’t saying that if you are on warfarin, there’s 1.5 higher odds you’ll get your knee or hip replaced than if you were on a direct oral anticoagulant,” says Dr. Shoor. This increased risk was for that small segment of people whose OA was advanced enough to have to get the joint replaced, he adds.
When to Discuss OA and Warfarin With Your Doctor
“If you’re concerned about the potential increased risk, talk to your doctor about it. If your primary care doctor isn’t aware of the research around this, you may have to see a specialist and let them make a recommendation on which medication is right for you,” says Shoor. This evidence isn’t enough to necessitate that everyone who has OA and is on warfarin should run to their doctor to get their medication switched, says Shoor. “This evidence shows that there’s a possibility of a relationship,” he says. The next steps for researching vitamin K and its role in OA progression are in the planning stages and will involve designing and launching an adequately powered randomized trial to test the efficacy of vitamin K supplementation for OA outcomes, wrote Ballal. RELATED: 10 Minutes of Walking a Day Can Be a Game-Changer for People With OA
Methotrexate Improves Function in Knee OA With Inflammation in Just Three Months, Data Suggests
New research to be presented on Monday, November 9, 2020, at the ACR Convergence found that three months of treatment with oral methotrexate, a drug used to treat inflammatory types of arthritis such as rheumatoid arthritis, led to significant improvements in physical function and inflammation in people with primary knee osteoarthritis (KOA). RELATED: Rheumatoid Arthritis Joint Pain Versus Osteoarthritis Joint Pain Many people with knee osteoarthritis have signs of joint inflammation, such as swelling, warmth and pain. The different therapies that can help improve inflammation all have varying degrees of benefits and drawbacks, according to Biswadip Ghosh, MD, associate professor in the department of rheumatology at the Institute of Post Graduate Medical Education and Research in Kolkata, India. For most patients, anti-inflammatory analgesic drugs (NSAIDs) like aspirin, diclofenac, or celecoxib work better than acetaminophen, which does not have anti-inflammatory activity, Dr. Ghosh wrote in an email message. “However, NSAIDs have side effects if used continuously,” he added. There is a risk of gastrointestinal bleeding associated with all NSAIDs, and that risk is higher for people who take them every day, according to the U.S. Food and Drug Administration (FDA). Steroids can be injected into the knee to reduce inflammation and reduce pain in knee osteoarthritis, but some people are afraid of needles, and repeated injections can lead to other problems, according to Ghosh.
Could Methotrexate Be a Smart Way to Treat Osteoarthritis?
To find out if oral methotrexate could be an effective way to treat OA, investigators compared it with a placebo treatment, glucosamine, a common supplement for arthritis pain relief. People could be included in the study if they had swelling and pain in both knee joints for at least six months, and also had evidence of OA on their X-rays. People were excluded if they had undergone arthroscopy, a steroid injection in their knee in the previous three months or if they had uncontrolled diabetes, gout, or liver or kidney disease. A total of 249 subjects with signs of local inflammation and increases in inflammatory markers in their blood samples were placed in the inflammatory group in the study and then randomly selected to receive 15 to 20 milligrams (mg) of oral methotrexate per week or 1500 mg of glucosamine, and were checked on once a month for three months. Those subjects were allowed to take acetaminophen or tramadol for pain if needed and were given NSAIDs for 7 to 10 days at the start of the trial to improve compliance.
Subjects With Knee Osteoarthritis Saw Improvement with Methotrexate
The study’s results showed that after three months, patients with primary knee OA with evidence of inflammation had significant improvements on the WOMAC (Western Ontario and McMaster Universities Arthritis) index, which measures pain, stiffness, and physical function, as well as a reduction in the inflammatory markers used in the study, which were erythrocyte sedimentation rate and C-reactive protein. People who took glucosamine had no significant improvement in these measures of function and inflammation.
Benefits of Methotrexate Include Low Cost, Convenience
The researchers concluded that methotrexate can be an effective intervention for people with knee OA who experience pain and inflammation. “Methotrexate is taken once in a week, so very convenient and inexpensive,” added Ghosh. “This study looks at methotrexate, a treatment that’s well accepted for rheumatoid arthritis in which the autoimmune inflammation is driving the disease and causing the joint damage, and looking at its efficacy in a disease where there may be some inflammation in a small set of people, and the inflammation takes place secondarily to this gradual inability of the cartilage cells to reproduce themselves,” Shoor explains.
What to Know if You Have Osteoarthritis
“These results are very preliminary, but the study is very interesting,” says Shoor. “From the abstract data that I see I don’t know how powerful the effect was,” he adds. Even though the subjects in this study experienced improvements, this medication would probably be appropriate for just a very small number of people, says Shoor. “I’m not convinced that many patients with this type of knee OA would want to take methotrexate for their osteoarthritis, in large part because of the very significant side effects,” he says. Although most of the side effects are short term and reversible, methotrexate can cause significant nausea and fatigue, says Shoor. “Elevation of liver enzymes or lowering of their blood cell counts sufficient are also common, and about 10 percent of patients experience hair loss as well,” he adds. “This drug can be an excellent medicine if used for rheumatoid arthritis with caution and surveillance, but when used for OA, it’s experimental,” says Shoor. “I would be interested to see the results of this study in more detail and see more research in the future that looks methotrexate in the small subset of people with OA with this type of inflammation,” he adds.
