Cardiovascular Outcomes of Disease-Modifying Antirheumatic Drugs in Rheumatoid Arthritis: A Review of the Current Evidence

Rheumatoid arthritis (RA) significantly increases the risk of cardiovascular disease (CVD), including myocardial infarction (MI), stroke, and heart failure (HF), with RA treatments influencing cardiovascular outcomes. This review analyses the cardiovascular effects of methotrexate, leflunomide, hydroxychloroquine, sulfasalazine, and TNF inhibitors (infliximab, etanercept, adalimumab, and certolizumab) in RA management, emphasizing their safety and risks in CVD. This narrative literature review was conducted using searches of the PubMed database from inception through January 2025. We included meta-analyses, systematic reviews, randomized controlled trials, observational studies, pharmacovigilance studies, and animal studies. Methotrexate offers cardiovascular benefits by reducing inflammation and improving endothelial function. However, it also raises homocysteine levels, which promote oxidative stress and endothelial injury - effects that can be mitigated by folic acid supplementation. Leflunomide's cardiovascular effects remain poorly defined, highlighting the need for further research. Hydroxychloroquine may prolong the QT interval, raising the risk of conduction disorders and necessitating monitoring in high-risk patients. Sulfasalazine shows potential cardiovascular benefits by inhibition of platelet aggregation, improved endothelial function, and reduced lipid levels, although more research is needed for conclusive evidence. TNF inhibitors, such as infliximab, etanercept, adalimumab, and certolizumab pegol, reduce inflammation-driven cardiovascular risks but are contraindicated in patients with severe HF (New York Heart Association [NYHA] classes III and IV).