Common Arthritis Drug Found To Lower Blood Pressure and Boost Heart Health

A widely used treatment for rheumatoid arthritis may offer an unexpected cardiovascular benefit.

Methotrexate has been a staple treatment for rheumatoid arthritis for decades, valued for its ability to calm an overactive immune system and reduce painful joint inflammation. Now, researchers say it may deliver an unexpected bonus that matters far beyond the joints: lower blood pressure, a change that could translate into meaningful protection against heart attacks and strokes for some patients.

A study led by teams at Flinders University and the Southern Adelaide Local Health Network (SALHN) reports that people newly diagnosed with rheumatoid arthritis who started methotrexate saw a significantly larger drop in blood pressure than those given sulfasalazine, another standard disease-modifying medication. Because elevated blood pressure is one of the strongest predictors of cardiovascular disease, even modest reductions can have outsized long-term benefits.

Rheumatoid arthritis (RA), which affects about one in 100 people, is best known for joint pain and swelling. But the disease also has whole-body effects. Persistent inflammation can influence blood vessels and the heart, which helps explain why cardiovascular disease is a leading cause of illness in people with RA. That makes any treatment that may improve both inflammation control and cardiovascular risk especially intriguing.

Study Design and Key Findings

To test whether methotrexate influences blood pressure early in the disease, researchers in South Australia and Italy followed 62 adults who had just been diagnosed and had not yet begun therapy. Half received methotrexate, while the other half took sulfasalazine.

Participants had their blood pressure measured at the start of the trial, then again after one month and six months. The team also tracked joint inflammation and arterial stiffness to see whether any blood pressure changes were simply a byproduct of improved arthritis control or healthier arteries.

Lead author Professor Arduino Mangoni, from Flinders University’s College of Medicine and Public Health and SALHN’s Department of Clinical Pharmacology, said the team focused on systolic blood pressure, which reflects how strongly blood presses against artery walls when the heart contracts.

“We found that methotrexate lowered systolic blood pressure by an average of 7.4 mmHg compared with people taking sulfasalazine,” says Professor Mangoni, Strategic Professor of Clinical Pharmacology.

“This kind of reduction is considered meaningful because even a small drop in blood pressure can lower the risk of serious heart problems like heart attacks and strokes.”

Notably, the reduction in blood pressure was not associated with changes in joint symptoms or improvements in arterial stiffness. This suggests the medication may benefit the cardiovascular system through other biological pathways, such as reducing systemic inflammation or enhancing blood vessel function.

Broader Implications for Treatment

According to Professor Arduino Mangoni of Flinders University’s College of Medicine and Public Health and SALHN’s Department of Clinical Pharmacology, the results point to a broader role for methotrexate in patient care.

“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 says.

“This could be a big step forward in how we care for people with rheumatoid arthritis.”

The researchers also investigated whether genetic differences influenced how patients responded to methotrexate. Their analysis showed that certain genetic variants were linked to a greater likelihood of experiencing a drop in blood pressure while taking the drug.

“In short, if someone has specific gene variants, methotrexate might add a heart health benefit to its usual role in treating rheumatoid arthritis by the positive effect on blood pressure,” he says.

The researchers say that this opens the door to more personalized treatment options, where doctors could use genetic testing to predict who might benefit most from methotrexate’s heart-protective effects.

Study coordinator and medical scientist, Dr. Sara Tommasi, sp;says that although more research is needed to confirm these findings and understand exactly how methotrexate lowers blood pressure, the results are promising.

“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,” says Dr Tommasi from the College of Medicine and Public Health and South Adelaide Local Health Network.

Reference: “A controlled comparative study of the effects of methotrexate and pharmacogenetic factors on arterial blood pressure and arterial stiffness in patients with rheumatoid arthritis” by Arduino A. Mangoni, Michael D. Wiese, Richard J. Woodman, Salvatore Sotgia, Angelo Zinellu, Ciriaco Carru, Julie-Ann Hulin, E. Michael Shanahan and Sara Tommasi, 31 July 2025, Annals of Medicine.
DOI: 10.1080/07853890.2025.2539311

This was an investigator-initiated study funded by medac GmbH (Germany). Medac GmbH had no involvement in the study design, study conduct, data collection, data analysis, data interpretation, or manuscript preparation.

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