Rheumatoid arthritis patients had nearly double the risk of any type of stroke and almost a three-fold increased risk of ischemic stroke compared with patients with a non-inflammatory rheumatic disease, Frederick Wolfe, M.D., of the National Data Bank for Rheumatic Diseases, and colleagues reported in the August issue of Arthritis Care & Research.
Ischemic stroke was independently predicted by hypertension (P=0.012), myocardial infarction (P=0.013), low-dose aspirin use (P<0.001), number of comorbidities (P<0.001), severity of rheumatoid arthritis as measured by occurrence of total joint replacement (P=0.017), and scores on the Health Assessment Questionnaire (P<0.001).
In general, common therapies for rheumatoid arthritis, including tumor necrosis factor-alpha (TNF) blockers, Cox-2 inhibitors, and nonselective nonsteroidal anti-inflammatory drugs, were not associated with stroke risk.
However, use of rofecoxib (Vioxx), which was withdrawn from market in September 2004, was marginally associated with an increased risk of ischemic stroke (OR 2.27, 95% CI 0.97 to 5.28, P=0.06).
Although some studies had found that cardiovascular and cerebrovascular diseases were more common in patients with rheumatoid arthritis, no studies have examined the effect of disease severity, treatment, or cardiovascular risk factors on stroke risk in these patients, according to the researchers.
To explore the issue, they examined data from the National Data Bank for Rheumatic Diseases on 16,990 adult rheumatoid arthritis patients and 5,141 control patients with non-inflammatory rheumatic disorders such as osteoarthritis, back pain syndromes, fibromyalgia, and tendinitis.
All participants completed at least two semiannual follow-up questionnaires from January 1999 through July 2006.
The researchers identified 269 strokes, including 67 ischemic strokes, at a mean age of 70.
They noted that patients with rheumatoid arthritis had a 1.64-fold (95% CI 1.16 to 2.30) greater risk of any type of stroke and a 2.66-fold (95% CI 1.24 to 5.70) increased risk of ischemic stroke compared with those with a non-inflammatory rheumatic disease
Stroke risk was not predicted by some traditional cardiovascular risk factors, including diabetes, smoking, lack of exercise, and high body mass index. The researchers said the reasons for the lack of an association with these risk factors was unclear.
Use of the corticosteroid prednisone immediately prior to stroke may have been associated with ischemic stroke in rheumatoid arthritis patients, the researchers said. The drug was not significantly associated with ischemic stroke in a multivariable analysis (P=0.114), but was significantly associated in a univariate analysis (OR 2.03, 95% CI 1.08 to 3.84, P=0.029).
The researchers said the findings related to prednisone were unclear and needed to be confirmed in future studies.
TNF blocker therapy was not associated with ischemic stroke (OR 0.80, 95% CI 0.34 to 1.82, P=0.584).
In general, in analyses examining the effects of rheumatoid arthritis treatments, significant associations in univariate analyses became nonsignificant in multivariate analyses.
"We did not find evidence to support the association of rheumatoid arthritis treatment and stroke, with the exception of rofecoxib and possibly antecedent prednisone," the researchers said.
They said that the effect of corticosteroids on stroke risk in rheumatoid arthritis patients was likely confounded by disease severity, "and it is likely that residual confounding remains even after the adjustments used in the current study."
The authors acknowledged some other limitations of the study, including the small number of ischemic strokes, potential residual confounding from other variables such as joint counts, radiographic erosions, and inflammatory markers, and the possibility that the degree of confounding changed over time because of differences in treatment.
| The National Data Bank for Rheumatic Diseases has conducted safety registries for Centocor, sanofi-aventis, and Bristol-Myers Squibb, and has received research grants from Abbott, Amgen, Wyeth-Australia, Merck, and Pfizer.
Dr. Wolfe has received consultant fees of less than ,000 from Bristol-Myers Squibb. |