Methotrexate and Other Antirheumatic Drugs Linked to Risk of Cardiovascular Events in Arthritis Patients

Methotrexate and tumor necrosis factor inhibitors may be associated with reduced risk of cardiovascular events in patients with rheumatoid arthritis, psoriatic arthritis, and psoriasis, according to a meta analysis of previous studies.

Tumor necrosis factor (TNF) inhibitors and methotrexate are associated with decreased risk of all cardiovascular events (CVEs) in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), or psoriasis (Pso), according to research published in the Annals of Rheumatic Diseases.

However, patients with those conditions who take nonsteroidal anti-inflammatory drugs (NSAIDs) or corticosteroids may be at increased risk for CVEs.

Researchers from the Institut de Rhumatologie de Montreal in Canada reviewed 34 studies collected from publication databases between 2010 and 2012 in order to determine the association between CVEs and anti rheumatic drugs in RA and PsA/Pso. The publications the researchers reviewed were controlled studies and randomized trials reported confirming CVEs in patients with RA or PsA/Pso treated with anti rheumatic drugs.

The researchers found from their review that TNF inhibitors were significantly associated with a reduction in the risk of all CVEs, as well as myocardial infarctions, strokes, and major adverse cardiac events. There were no significant heart failures observed. The researchers termed the association between methotrexate and reduction in the risk of all CVEs and myocardial infarction a “beneficial association.” However, methotrexate was not associated with a significant decrease in the risk of strokes and major adverse.

NSAIDs increased the risk of all CVEs and strokes, which was apparently driven by cyclooxygenase-2 (COX-2) inhibitors rather than non selective NSAIDs. Some studies in the review assessed rofecoxib, which has already been withdrawn from the market, the researchers noted, so they performed separate analysis for rofecoxib and celecoxib. Rofecoxib increased the risk of all CVEs, while celecoxib did not. NSAIDs did not have a significant effect on myocardial infarction, heart failure, or major adverse cardiac events. The researchers cautioned, though, that the results of the analysis should be interpreted with caution because of the small study sample.

The researchers were only able to assess 6 studies for their effects on patients with PsA/ Pso. Systemic therapy was associated with a significant decrease in all of CVEs in PsA/ Pso.

“In patients with RA, treatment with TNF inhibitors or methotrexate was associated with a 30 percent and 28 percent reduction in the risk of CVEs, respectively, while use of NSAIDs or corticosteroids was associated with 18 percent and 47 percent increase in risk of all CVEs, respectively,” the authors summarized.

“Moreover, while TNF inhibitors and methotrexate were also found to be associated with a reduction in risk of some specific cardiovascular endpoints, corticosteroids were associated with an increase in risk of all specific outcomes. In patients with Pso/PsA, data suggest that biologics and other DMARDs may be associated with a decreased risk of CVEs, but we acknowledge that evidence is less conclusive than in RA and that further studies are needed,” the authors concluded.