RESEARCH - Impact of immunosuppressive medications on cardiovascular events in RA patients

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Medscape Rheumatology

From ARTHRITIS & RHEUMATISM Research News Alerts

Posted 01/19/2007

The Impact of Immunosuppressive Medications on Cardiovascular Events in

Rheumatoid Arthritis Patients

Patients with rheumatoid arthritis (RA) have an increased risk of heart

attack and stroke. According to extensive evidence, the key driver for this

increased risk of cardiovascular disease is the increased systemic

inflammation characteristic of RA. Studies are less clear on whether

medications that work to reduce RA's inflammatory symptoms provide

protective benefits against cardiovascular events. Some data have suggested

that the most potential biologic therapies, such as the TNF blockers, might

reduce the risk of ischemic cardiovascular events.

To investigate, researchers at Harvard Medical School's Brigham and Women's

Hospital compared the effects of a variety of immunosuppressive agents on

cardiovascular events in a large sample of RA patients. Based on their

findings, featured in the December 2006 issue of Arthritis & Rheumatism

(http://www.interscience.wiley.com/journal/arthritis), TNF blockers were not

associated with either a reduction or an increase in the risk of heart

attack or stroke compared with the most commonly used RA treatment,

methotrexate. While certain anti-inflammatory drugs appeared to exacerbate

the risk of heart attack and stroke for RA patients, particularly among

older women.

Drawing on a database of Medicare patients receiving a drug benefit from the

state of Pennsylvania, the researchers identified 946 individuals who had

been diagnosed with RA, prescribed an immunosuppressive agent, and

hospitalized for either heart attack or stroke within a six-year period.

These patients were defined as case subjects for studying the role of

anti-inflammatory RA therapies in the risk of cardiovascular disease. Each

case subject was matched by age and gender to ten controls. The controls, a

total of 9,460 RA patients, did not experience cardiovascular events during

the delineated period. All the subjects were over age 65 and most were

female and white. Current therapy was defined by having a prescription

filled 90 days prior to the date of the case subject's first cardiovascular

event. Researchers then categorized the different drugs and analyzed their

relationship to heart attack and stroke using standard risk regression

models. Methotrexate (MTX) was considered individually and, as the most

widely prescribed immunosuppressive agent, used as the reference group for

other therapies.

Compared with MTX, researchers found neither a protective nor detrimental

cardiovascular impact for biologic agents, including the interleukin-1

receptor antagonist anakinra as well as the three TNF blockers, adalimumab,

etanercept, and infliximab. Oral glucocorticoids, steroid hormones like

prednisone, were associated with a 50 percent increase in the probability of

a cardiovascular event when taken alone; a similar trend in the direction of

risk was seen with glucocorticoids combination therapy. Most significantly,

cytotoxic agents, also known as disease-modifying antirheumatic drugs

(DMARDs), were found to increase the likelihood of heart attack or stroke by

80 percent when used without other drugs. This finding applied to

azathioprine, cyclosporine, and leflunomide.

, MD, MPH, the study's lead author and Associate Professor of

Medicine at Brigham and Women's Hospital and Harvard Medical School,

acknowledges that this study has several limitations. Given the data

source-a huge healthcare utilization database-it was difficult to assess the

severity of RA and the contribution of other cardiovascular risk factors,

such as smoking and diet. Furthermore, the subjects were primarily elderly,

with a mean age of 82, and in a frail state of health. " Experimental

designs, such as randomized clinical trials, would be very useful to better

understand the effects of these agents on cardiovascular outcomes among

patients with RA, " Dr. reflects.

http://www.medscape.com/viewarticle/550576

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