Methotrexate May Lower Blood Pressure in Rheumatoid Arthritis

Methotrexate, a cornerstone treatment for rheumatoid arthritis (RA), may also offer an unexpected cardiovascular benefit.1 New findings from a controlled comparative study showed the drug significantly lowers systolic blood pressure (SBP) in adults with newly diagnosed RA, compared with sulfasalazine, another disease-modifying antirheumatic drug (DMARD). The study, published in Annals of Medicine, followed 62 treatment-naïve patients with RA over 6 months, with half receiving subcutaneous methotrexate and the other half oral sulfasalazine. Researchers measured changes in blood pressure, arterial stiffness, and disease activity. By 6 months, patients treated with methotrexate had a mean reduction in systolic blood pressure of 7.4 mm Hg compared with those taking sulfasalazine (95% CI, –14.0 to –0.8; P = .03). Lead author Arduino A. Mangoni, MD, PhD, strategic professor and head of clinical pharmacology at Flinders University, called the reduction clinically meaningful, as reducing blood pressure can in turn reduce the risk of serious cardiovascular events such as heart attacks and strokes.2 “We’ve known for a while that methotrexate helps with inflammation, but now we’re seeing that it may also help lower blood pressure, which is a major risk factor for heart disease,” he said in a news release.2 “This could be a big step forward in how we care for people with rheumatoid arthritis.” Cardiovascular Risk in RA RA affects approximately 1 in 100 people worldwide and is associated with systemic inflammation, endothelial dysfunction, and a heightened risk of cardiovascular disease. Hypertension and arterial stiffness are common comorbidities, increasing the likelihood of heart attacks and strokes among individuals with RA. Past observational studies have linked methotrexate to reductions in cardiovascular-related mortality and morbidity in autoimmune disease populations.1 However, those studies did not establish causality. Although the latest findings do not establish a clear causal relationship, they do provide prospective comparative evidence that methotrexate lowers SBP in patients with RA, independent of improvements in joint disease activity or arterial stiffness. According to the researchers, this suggests the DMARD might be helping the heart by calming inflammation or improving blood vessel activity. “This proposition is further supported by the lack of between-group differences in the use of other drugs affecting blood pressure, e.g., antihypertensive medications, corticosteroids, and nonsteroidal anti-inflammatory drugs,” they said. Genetic Influence on Treatment Response Researchers also examined whether genetic variations influenced blood pressure outcomes. They found that patients with certain single nucleotide polymorphisms (SNPs), including rs1801133 in the MTHFR gene and rs2231142 in the ABCG2 gene, experienced greater reductions in blood pressure while on methotrexate. These findings suggest a potential role for pharmacogenetics in tailoring RA treatment. “The specific associations between rs1801133 (MTHFR) and rs2231142 (ABCG2) and blood pressure changes during methotrexate treatment are supported by the concomitant lack of associations between these SNPs and blood pressure changes with sulfasalazine,” the authors noted. It’s important to note treatment allocation was not randomized but based on clinical judgment, raising the potential for confounding by indication. Additionally, the sample size was relatively small, and patient attrition was higher in the sulfasalazine group. “The results suggest that this well-known arthritis drug could also play a role in protecting heart health, especially in people who are at higher risk due to inflammation,” said Sara Tommasi, PhD, study coordinator and medical scientist at Southern Adelaide Local Health Network, in the news release. References