From the Guidelines
Rheumatoid arthritis (RA) does increase the risk of blood clots, with patients having approximately a 2-3 times higher risk of developing venous thromboembolism compared to the general population, as supported by the most recent evidence from 1. This elevated risk stems from several factors, including:
- The chronic inflammation associated with RA, which activates the coagulation system
- Reduced mobility during disease flares
- Certain medications used to treat RA, particularly JAK inhibitors like tofacitinib (Xeljanz), baricitinib (Olumiant), and upadacitinib (Rinvoq), which carry FDA warnings about increased clot risk, as noted in 1 To manage this risk, patients should:
- Stay physically active as able
- Maintain good hydration
- Avoid smoking
- Discuss prophylactic measures with their doctor if they have additional risk factors During periods of hospitalization or immobility, preventive anticoagulation may be recommended, as suggested by 1 Patients taking JAK inhibitors should be particularly vigilant about symptoms of blood clots, including leg swelling, pain, warmth, redness, or sudden shortness of breath, and seek immediate medical attention if these occur, as advised in 1 Regular follow-ups with rheumatologists are essential to monitor disease activity and medication effects, as emphasized in 1 and 1
From the Research
Rheumatoid Arthritis and Clot Risk
- Rheumatoid arthritis (RA) is a systemic inflammatory autoimmune disease that can increase the risk of cardiovascular disease, including myocardial infarction, stroke, and heart failure 2.
- The disease-modifying antirheumatic drugs (DMARDs) used to treat RA, such as methotrexate, leflunomide, hydroxychloroquine, sulfasalazine, and TNF inhibitors, can influence cardiovascular outcomes 2.
- Methotrexate, a commonly used DMARD, can reduce inflammation and improve endothelial function, but it can also raise homocysteine levels, which can promote oxidative stress and endothelial injury 2.
- Hydroxychloroquine may prolong the QT interval, raising the risk of conduction disorders and necessitating monitoring in high-risk patients 2.
- Sulfasalazine shows potential cardiovascular benefits by inhibiting platelet aggregation, improving endothelial function, and reducing lipid levels, although more research is needed for conclusive evidence 2.
- TNF inhibitors can reduce inflammation-driven cardiovascular risks but are contraindicated in patients with severe heart failure 2.
- Patients with RA are at greater risk for serious infection, respiratory disease, osteoporosis, cardiovascular disease, cancer, and mortality than the general population 3.
- Early diagnosis, aggressive treatment, and expanded therapeutic options of DMARDs have markedly improved both the management and long-term prognosis of RA 3.
Disease-Modifying Antirheumatic Drugs and Clot Risk
- Methotrexate is still considered the anchor drug among DMARDs and is widely accepted as first-line treatment in the management of RA 4, 5.
- Combination DMARD therapy, including methotrexate and other DMARDs such as leflunomide, cyclosporine, azathioprine, sulfasalazine, gold, and hydroxychloroquine, may be used to treat patients with RA who fail to respond to monotherapy 5.
- Low-dose glucocorticoids combined with methotrexate and hydroxychloroquine can achieve disease remission and improve clinical and radiological outcomes in early RA patients, without enhancing adverse reactions 6.