NEW YORK – Tumor necrosis factor inhibitors reduced the risk of myocardial infarction, stroke, and cardiovascular-related disease in patients with rheumatoid arthritis, according to Dr. Jeffrey D. Greenberg, who presented the findings at the meeting. 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 CV-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) praised the study's methodology and transparency. But they noted that other studies, like those published by the British Society for Rheumatology Biologics Register (BSRBR), do not support a CV protective effect for TNF inhibitors.
Nonbiologic disease-modifying antirheumatic drugs (DMARDs) other than methotrexate served as the reference cohort for all comparisons. Relative to nonbiologic DMARDs, methotrexate use was associated with a nonsignificant reduction in risk (hazard ratio 0.83, 95% confidence interval C0.44–1.57). In contrast, patients using a TNF inhibitor had a 61% lower risk of the primary composite CV end point (HR 0.39, 95% CI 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, 95% CI 0.19–0.82) and a composite end point that excluded CV deaths (HR 0.35, 95% CI 0.16–0.74), and nonfatal MI (HR 0.24, 95% CI 0.06–0.95). There was a trend toward reduced risk for nonfatal TIA/stroke (HR 0.44, 95% CI 0.18–1.09). “These data indicate that TNF antagonists may represent a therapeutic strategy to attenuate the heightened CV risk experienced by RA patients,” Dr. Greenberg said.
“As expected, there was a dose-dependent increased risk of CV events with steroids,” said Dr. Greenberg of New York University. Prednisone dosesbof 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, 95% CI 1.44–6.25) (p = 0.04).
Dr. Greenberg advocates a three-step strategy to decrease CV risk in RA. The first is to adhere to recommended CV disease prevention, screening, and guidelines. This includes management of “traditional” CV 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 steroids, 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 CV disease. Measures that should be targeted might include a specific disease activity score, C-reactive protein levels, or other inflammatory biomarkers, he said.