Use of tumor necrosis factor antagonist agents significantly reduced the risk of cardiovascular events in rheumatoid arthritis patients, according to an analysis of data from more than 10,000 patients.
Although previous studies have not shown that anti-TNF therapy reduces the risk of cardiovascular events in RA patients, "promising results for improving cardiovascular outcomes with TNF antagonist use have been reported by two European studies," Dr. Jeffrey D. Greenberg of New York University and colleagues wrote in the April Annals of the Rheumatic Diseases.
In this North American study, patients who used TNF antagonists had a 61% lower risk of a primary end point of composite cardiovascular events (HR, 0.39), compared with reference patients who used nonbiologic disease-modifying antirheumatic drugs (DMARDs). The researchers analyzed data from 10,156 patients enrolled in the Consortium of Rheumatology Researchers of North America (CORRONA) RA registry between Oct. 1, 2001, and Dec. 31, 2006. The average age of the patients was 59 years and 75% were women (Ann. Rheum. Dis. 2011;70:576-82).
During the study period, the researchers identified 88 composite cardiovascular events including 26 myocardial infarctions, 45 strokes or transient ischemic attacks, and 17 cardiovascular-related deaths. The incidence rate for composite cardiovascular events in patients who used TNF antagonists was 2.93/1,000 patient-years of exposure, compared with 6.73/1,000 patient-years for methotrexate and 7.51 for the reference group of patients who used DMARDs.
Methotrexate use did not have a significant impact on reducing cardiovascular risk. However, prednisone use was significantly associated with an increasing risk for cardiovascular events, compared with nonuse, the researchers noted.
When the researchers examined specific cardiovascular events, TNF antagonist use was associated with a significantly lower risk of myocardial infarction and a trend toward a significantly lower risk of transient ischemic attack or stroke.
The mechanism by which TNF antagonists could reduce cardiovascular risk remains unclear. Data suggest that TNF antagonists might stabilize atheromatous plaques, while other results have shown improved flow-mediated vasodilation and endothelial function associated with TNF antagonists, the researchers said.
Additional studies are needed to assess the role of inflammation in populations at increased risk for cardiovascular events, the researchers wrote. But "TNF antagonist drugs may represent a promising therapeutic strategy to attenuate the heightened cardiovascular risk associated with RA," they wrote.
In an editorial accompanying the report, Dr. Johan Askling and Dr. Will Dixon said that one of the unanswered questions in studying the relationship between anti-TNF therapy and a reduced risk of cardiovascular events is whether the risk reduction is only a shift in the risk between different subsets of patients.
The dramatic reduction in cardiovascular risk in the anti-TNF group could be due to a higher incidence of cardiovascular events in patients who do not receive anti-TNF therapy for any reason, the investigators said. More studies in other RA populations are needed, and might explain the disparate results seen in previous studies of anti-TNF and cardiovascular risk, they noted (Ann. Rheum. Dis. 2011;70:561-2).
"As evidence accumulates in this important topic, we move closer towards a true understanding of the effect of drug therapies on cardiovascular outcomes," said Dr. Askling of Karolinska University, Stockholm, and Dr. Dixon of the University of Manchester (England).
Disclosures were not provided for Dr. Askling and Dr. Dixon. Dr. Greenberg said he has received research grants from the National Institutes of Health, the Arthritis Foundation, and Bristol-Myers Squibb. He has served on advisory boards from multiple pharmaceutical companies including Centocor, Genentech, and Roche.