BOSTON, Massachusetts—Combination therapy with a TNF-inhibitor plus methotrexate (MTX) slashes heart attack risk by 80% in rheumatoid arthritis (RA) patients, compared with those patients receiving MTX monotherapy. The new findings were presented at the American College of Rheumatology Annual Scientific Meeting in Boston.

"Perhaps treatment that has strong effects on reducing inflammation may have beneficial effects on the heart," said lead researcher Gurkirpal Singh, MD, an adjunct clinical professor of medicine, division of gastroenterology and hepatology at Stanford University School of Medicine in Palo Alto, California. "Inflammation in RA is important in the joints and the heart and one needs to be aggressive in the treatment of RA to prevent serious complications," he said. "We need to do this for our patients to save their lives, not just improve the quality of their lives."

Using data from MediCal, the Medicaid program for California, researchers tracked the risk of acute myocardial infarction in 19,233 RA patients using a TNF-inhibitor, MTX, and other disease modifying antirheumatic drugs (DMARDs) over 6.5 years. Many study participants were also taking concomitant aspirin. The patients had a mean age of 55, and approximately 79% were female.

80% risk reduction seen in TNF/MTX group

Of these patients, 13,383 took MTX; 14,958 took other DMARDS; and 4943 took TNF-inhibitors. Exposure to TNF-inhibitors taken alone or in combination with MTX was compared with MTX alone. Overall, 441 patients had heart attacks, of which 8% were fatal, during 74,006 person-years of follow-up. RA patients on a combination of TNF-inhibitors with MTX had only a 20% risk of heart attack compared with patients taking MTX monotherapy, the study showed. "We think [combination therapy] normalizes [heart] risk [in RA patients] to that of the general population," Dr. Singh said.

There was no statistical difference seen among patients who were taking TNF-inhibitors alone, TNF-inhibitors with other DMARDs, other DMARD therapies without MTX, or a combination of DMARDs and MTX. Systemic corticosteroid use significantly increased the risk of heart attack. Dr. Singh said that future studies will investigate whether there are any differences in risk reduction seen among the different TNF-inhibitors.

Daniel H. Solomon, MD, MPH, an associate physician at Brigham and Women's Hospital in Boston said that "rheumatologists focus on arthritis, but systemic inflammation can affect systems outside of the joints. The morbid associations with extraarticular manifestations [of RA] are substantial, and we hope, preventable."

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