NEW YORK – Tumor necrosis factor inhibitors reduced the risk of myocardial infarction, stroke and cardiovascular-related death in patients with rheumatoid arthritis, according to Dr. Jeffrey D. Greenberg, who presented the findings at a rheumatology meeting sponsored by New York University. Methotrexate was not associated with a reduced risk of cardiovascular events, and prednisone use was associated with a dose-dependent increased risk.
The findings come from CORRONA (Consortium of Rheumatology Researchers of North America), a registry of patients with RA or psoriatic arthritis. The study population involved 10,156 patients followed for a median of 23 months. A subset analysis was performed, and 88 patients were identified who had experienced nonfatal myocardial infarction (n = 26), transient ischemic attack or stroke (n = 45), or cardiovascular-related death (n = 17) (Ann. Rheum. Dis. 2011;70:576-82).
In an editorial accompanying Dr. Greenberg’s report (Ann. Rheum. Dis. 2011 70:561-2), Dr. Johan Askling of Karolinska University Hospital, Stockholm, and Dr. Will Dixon of the University of Manchester (England) praiseed Dr. Greenberg’s study in terms of its methodology and transparency. However, they point out that other studies, such as those published by the British Society for Rheumatology Biologics Register (BSRBR), have not supported a cardiovascular protective effect for TNF inhibitors.
Nonbiologic disease-modifying antirheumatic drugs (DMARDs) other than methotrexate served as the reference cohort for all therapeutic comparisons. Relative to nonbiologic DMARDs, methotrexate use was associated with a nonsignificant reduction in risk (HR 0.83, 95% CI 0.44-1.57). In contrast, patients using a TNF inhibitor had a 61% reduced risk of the primary composite cardiovascular end point (HR 0.39, 0.18-0.74).
Dr. Greenberg also showed significant reductions in risk for those taking TNF inhibitors compared with those taking nonbiological DMARDs as measured by a composite end point that included CV deaths (HR = 0.39, 0.19-0.82) and a composite end point that excluded CV deaths (HR = 0.35, 0.16-0.74), and nonfatal MI (HR = 0.24, 0.06-0.95). There was a trend toward reduced risk for nonfatal TIA/stroke (HR = 0.44, 0.18-1.09). "These data indicate that TNF antagonists may represent a therapeutic strategy to attenuate the heightened cardiovascular risk experienced by RA patients," Dr. Greenberg said.
"As expected, there was a dose-dependent increased risk of cardiovascular events with steroids," said Dr. Greenberg of New York University. Prednisone doses between 1-2.5 mg and 3-7 mg almost doubled the risk (HR 1.90 and 1.89, respectively) while doses greater than 7 mg tripled the risk (HR 3.00, 1.44-6.25) (P = .04).
Dr. Greenberg advocates a three-step strategy to decrease cardiovascular risk in RA.
The first is to adhere to recommended cardiovascular disease prevention, screening, and guidelines. This includes management of "traditional" cardiovascular risk factors such as blood pressure, diabetes, lipids, smoking, and obesity, he said.
The second component – as supported by his study’s results – is to minimize use of NSAIDs and corticosteroids, and to utilize steroid-sparing options if possible.
The third component is to aim for tighter control of RA disease activity. For patients at increased CV risk, "I would treat RA aggressively," said Dr. Greenberg. Even so, he acknowledged that it has not been proved that the strategy would alter the natural course of developing cardiovascular disease. It remains to be determined what measures should be targeted, he said, suggesting options such as a specific disease activity score, C-reactive protein levels, or other inflammatory biomarkers.
Indeed, the lack of CV risk assessment tools and evidence-based practice guidelines for improving cardiovascular risk management in RA patients is getting a lot of attention.
Dr. Sherine E. Gabriel and researcher Cynthia S. Crowson of the Mayo Clinic, Rochester, Minn., discussed the limitations of both the SCORE and Framingham Risk Scores (Ann. Rheum. Dis. 2011;70:719-21). While applauding the European League Against Rheumatism (EULAR) for formulating guidelines to improve cardiovascular management in patients with RA, the researchers point out several areas of weakness. Cardiovascular disease risk, for example, is not necessarily associated with longer disease duration. In fact, studies show there is an increased risk of cardiovascular events early in the course of RA, they noted. The risks also are unclear for patients who are RF negative or ACPA negative. Further, RA patients may respond atypically to traditional cardiovascular risk factors.
Dr. Greenberg has done consulting for Centocor, CORRONA, Novartis Pharmaceutical Corp, Roche Laboratories, and UCB. He has received research and grant support from the Arthritis Foundation and the National Institutes of Health. He receives consulting fees from, or owns stock shares in, AstraZeneca, CORRONA, Genentech, Novartis, and Pfizer.