According to Dr. Solomon, the authors in the Rao study “examined the change in DAS28 after 24 weeks on TCZ as a potential correlate of cardiovascular risk. In adjusted models, they found that greater reductions in disease activity after starting TCZ were associated with a lower risk of cardiovascular events. It is unclear if this association is specific for TCZ or would hold for other effective RA treatments. A randomized controlled trial comparing the effects on cardiovascular risk for effective RA treatment strategies is a critical need in our field,” he says.
He and Dr. Liao note that an ongoing phase IV trial is looking into these issues. The clinical outcomes study is evaluating the rate of primary major adverse cardiac events, a composite of cardiovascular death, nonfatal myocardial infarction and nonfatal stroke, in patients with moderate to severe RA who are being treated with either TCZ or etanercept. The randomized, open-label, parallel-group, multicenter study is expected to be complete in October 2016.
Other observational studies are also being conducted and are comparing cardiovascular risk in patients receiving tocilizumab as compared with patients being treated with other biologic DMARDs.
Exploring the Paradox
A review article by Ernest Choy, MD, et al published in Rheumatology noted that “high inflammatory burden associated with RA appears to be a key driver of the increased cardiovascular risk.”3 This heightened inflammation accelerates atherosclerosis and exacerbates both established and novel cardiovascular risk factors, they said. An increasingly recognized paradox for physicians treating patients with RA is that cholesterol is inversely related to risk of cardiovascular disease in patients with RA who are not treated.
A study published in 2011 by Myasoedova et al found evidence that patients with lower total cholesterol and LDL levels and lower atherogenic ratios (ratio of total cholesterol to LDL cholesterol) have an increased risk of cardiovascular disease.4 In that population-based RA-incident cohort with 651 patients, ESR was also associated with risk of cardiovascular disease. Results of this research, the authors said, suggest that the “associations of lipid with [cardiovascular disease] in RA may be confounded by inflammation.”
Beyond the need for trials that compare the efficacy of RA treatment strategies for lowering cardiovascular risk, more data are needed about the role of inflammation and lipids on the cardiovascular risk among patients with RA, Drs. Liao and Solomon say.
They say that it’s possible, as reported in the Rao study, that disease activity “will be an important risk factor, while total cholesterol and LDL levels may be suboptimal measures to guide [cardiovascular] risk estimation and preventative interventions, because the levels appear to fluctuate with therapy in an inverse manner.”
