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This article discusses the rationale and design of the study "Methotrexate, blood pressure, and arterial function in rheumatoid arthritis". The recognition that immune activation and excess inflammation favor atherosclerosis has stimulated a significant body of research not only to identify new drugs targeting these pathways but also to repurpose (reposition) existing immunomodulatory medications as atheroprotective agents. Observational studies in patients with rheumatoid arthritis have reported that treatment with methotrexate, a traditional disease-modifying antirheumatic drug, is associated with a significantly lower risk of cardiovascular morbidity and mortality when compared with other disease-modifying antirheumatic drugs. One potential mechanism accounting for the reduced cardiovascular risk associated with methotrexate is the lowering effect on arterial blood pressure. However, such effect has only been observed in cross-sectional and observational studies. Given the established role of hypertension as a leading cardiovascular risk factor, these observations justify an intervention comparison study, the focus of this article, investigating the temporal effects of methotrexate on blood pressure and various surrogate markers of atherosclerosis in patients with rheumatoid arthritis. The results of this study might lead to the repurposing of methotrexate for cardiovascular prevention in patients with and without autoimmune disorders. Clinical Trial Registration:NCT03254589 (ClinicalTrials.gov). Plain Language Summary This article describes a research study looking at the effects of a well-established antirheumatic drug, methotrexate, on blood pressure and blood vessels in patients with rheumatoid arthritis, a disabling condition affecting the joints as well as other organs and tissues. Methotrexate is commonly used in rheumatoid arthritis, given its ability to suppress inflammation and the activation of the immune system. However, excessive inflammation and immune activation are linked to atherosclerosis, a condition characterised by the build-up of plaques in blood vessels and the development of clots. Therefore, methotrexate might also be helpful in combating atherosclerosis because of its ability to suppress inflammation and immune system activation. We have previously observed that patients with rheumatoid arthritis receiving methotrexate have lower blood pressure when compared with patients receiving other antirheumatic drugs. However, in this study we could not prove that methotrexate directly reduces blood pressure. Given that high blood pressure is well known to damage the blood vessels and promote atherosclerosis and its devastating manifestations, for example, heart attack and stroke, this article will discuss a new study that compares blood pressure for individuals assigned to different treatments to assess whether methotrexate can lower blood pressure over time and exert additional beneficial effects on blood vessels in patients with rheumatoid arthritis. The results of this study will be helpful in determining whether methotrexate can be routinely used to combat atherosclerosis and consequently reduce the risk of heart attack and stroke in patients with rheumatoid arthritis and, potentially, other patient groups. Article highlights There is an ongoing search for new drugs and the repurposing of marketed drugs with immunomodulatory effects conferring atheroprotection. The study "Methotrexate, blood pressure and arterial function in rheumatoid arthritis" will investigate whether methotrexate reduces blood pressure and markers of atherosclerosis in patients with rheumatoid arthritis. The results of this study will be helpful to determine whether methotrexate can be repurposed for cardiovascular prevention. [ABSTRACT FROM AUTHOR] |
