The risk of cardiovascular disease (CVD) is increased in patients with rheumatoid arthritis (RA), similar to the risk seen in diabetes mellitus. Lipid-lowering agents such as statins are known to decrease cardiovascular events. Indications for statins for primary prevention are usually determined by serum lipid levels and cardiovascular risk scores. However, several studies have shown that these risk scores tend to underestimate risk in RA patients. In addition, lipid levels may have a paradoxical effect in RA, with higher CVD risk in patients with low LDL or total cholesterol (abstract#2127). Should statins be started in all RA patients regardless of their lipid levels?
The TRACE RA study (abstract#2126) is a randomized, double-blind, multicentre trial that investigated whether atorvastatin 40 mg daily vs placebo decreases CV events in RA patients with no prior CVD and not requiring lipid-lowering agents for other reasons. This was the largest RCT ever conducted in RA with 2986 patients from 102 centres. However, the trial was stopped early because of a lower than expected CV event rate. Based on a prior study, the investigators expected 1.8% of patients to experience a CV event, but the observed rate was 0.7% after a median follow-up of 2.5 years.
The good news is that we may be doing a better job at managing co-morbid CVD in our RA patients. On the other hand, a large proportion of the observed risk could be due to patients with pre-existing CVD or high LDL, who were excluded from the trial. The bad news is that the shortened trial was underpowered to detect a difference in the treatment groups. In addition, the randomization was incompletely effective in that the groups differed with respect to smoking, NSAID utilization and ethnicity.
Not surprisingly, atorvastatin decreased LDL levels significantly, comparable to statin trials in other patient populations. There were 24 events in the atorvastatin group and 36 events in the placebo group, which did not reach statistical significance. When the investigators accounted for differences between the two groups in terms of medication compliance and non-study statin use, the hazard ratio for CV events was 0.54 (95% CI 0.30-0.99,P=0.045). There were no significant differences in adverse events between the two groups. It is controversial that the investigators included compliance and non-study statin use in the multivariable analysis.
Would you prescribe statins for all your RA patients based on this study?
Lillian Barra is an Assistant Professor at Western University. Her research interests include autoimmune vascular disease and the role of autoantibodies in rheumatoid arthritis.
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