NEW YORK — Patients with rheumatoid arthritis and elevated C-reactive protein levels would be likely to benefit from treatment with a statin to lower their CRP levels and consequently their risk for a cardiovascular event, regardless of their cholesterol levels, according to Dr. Jeffrey Greenberg.
This insight comes from a review of data from the 2008 JUPITER (Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin) study of almost 18,000 people, all of whom had high-sensitivity CRP (hs-CRP) levels above 2 mg/L, but relatively normal LDL cholesterol levels of less than 130 mg/dL. They were randomized to either 20 mg rosuvastatin or placebo.
The trial planned to run 5 years, but it was stopped after 2 years when the statin dropped LDL cholesterol levels by 50% on average, while CRP levels dropped by 37%. Of clinical note, the patients on the statin had significantly fewer episodes of nonfatal myocardial infarction, any MI, nonfatal stroke, and any stroke (N. Engl. J. Med. 2008;359:2195-207).
Although, strictly speaking, the findings from JUPITER cannot be extrapolated to rheumatoid arthritis patients, “clinical trials of this magnitude are rarely conducted in RA populations,” noted Dr. Greenberg.
Another compelling finding concerning the role of hs-CRP in increasing heart disease risk emerged after Dr. Greenberg's presentation: It was reported from the American College of Cardiology's annual meeting that JUPITER investigators doing subset analysis said that the effect of the statin on lowering the risk for cardiac events stemmed from its hs-CRP-lowering properties, rather than from its effect on cholesterol.
During his presentation, Dr. Greenberg, associate director of clinical and translational sciences in the division of rheumatology at New York University Medical Center, reviewed an earlier trial's findings suggesting that statins can act like a DMARD in RA. TARA (Trial of Atorvastatin in Rheumatoid Arthritis) involved 116 patients, randomized to placebo or 40 mg atorvastatin for 6 months. All patients were on DMARD therapy and some were taking a corticosteroid. Use of a statin reduced all components of their disease activity score, including erythrocyte sedimentation rate, hs-CRP level, swollen joint count, and plasma viscosity (Lancet 2004;363:2015-21).
Cardiovascular disease is the leading cause of death in patients with RA, and is estimated to account for 50% of mortality in that group. Mounting evidence suggests that the inflammation of the RA disease process acts on coronary vessels, increasing fatty streak deposition and contributing to the accumulation and possible rupture of plaque, Dr. Greenberg noted.
Findings from recent studies suggest that RA patients are more likely than other patients with CVD to have silent myocardial infarctions and sudden death (Arthritis Rheum. 2005;52:402-11). Another study found that RA patients who present with acute coronary syndrome may be more likely than other patients to have a second event and not to survive it (Ann. Rheum. Dis. 2006;65:348-53).
Given RA patients' increased risk for CVD and its propensity for atypical presentation, physicians must increase their vigilance to identify risk factors and intervene to lower them, he said. In addition to statin therapy, RA patients are likely to benefit from smoking cessation. Like other patients with CVD, they also should be advised to lose weight.