Study results presented at the 2014 American Thoracic Society International Conference show that treatment with rosuvastatin reduces markers of inflammation in patients with COPD after 12 weeks, but is not associated with improvements in measures of lung function.
While several observational studies have indicated that statins are beneficial in patient with COPD, no randomized controlled trials have evaluated the effect of statins on vascular and pulmonary function in these patients.
The RODEO trial looked at the effects on forced expiratory volume in 1 second (FEV1) and other measures of lung function in patients with COPD treated with rosuvastatin for 12 weeks.
In a presentation at the 2014 American Thoracic Society International Conference, Anke Neukamm, MD, of Akershus University Hospital in Norway, presented results from the RODEO trial and referred to previous observational studies and a more formal study by members of their group. In the current trial, conducted at two centers in Norway, Neukamm’s group tested the hypothesis that statin therapy is associated with improved endothelial and pulmonary function and reduced systemic inflammation in patients with stable COPD.
Exacerbations of COPD are associated with systemic inflammation, especially characterized by increases in circulating C-reactive protein (CRP). Endothelial function is also impaired in these patients. The pleiotropic immunomodulatory effects of statins appear to be independent of their lipid lowering properties.
The primary endpoint of the study was the change in vasodilator function measured by peripheral arterial tonometry, using the EndoPAT™ system, and expressed as the reactive hyperemia ratio (RHI).
The pre-specified subgroup of patients with elevated hsCRP values (>1.7 mg/L) at baseline warrants further evaluation since the rosuvastatin-treated subjects showed a significant improvement in RHI (p=0.026) versus placebo patients.
Secondary endpoints were changes in pulmonary function, as assessed by FEV1 and the FEV1/FVC ratio, and changes in the circulatory proinflammatory markers interleukin 6 (IL6) and high sensitivity C-reactive protein (hsCRP).
The study randomized a total of 99 patients. There were 5 withdrawals resulting in 47 patients evaluated per group (rosuvastatin treatment versus placebo). The mean age was 65 years and 48% of subjects were women.
Exclusion criteria included other diagnosed lung disease except asthma, coronary artery disease, uncontrolled hypertension, hypercholesterolemia, diabetes and recent statin therapy.
As the researchers expected, lipid levels decreased in the rosuvastatin group (LDL cholesterol p<0.001). No significant differences in endothelial (vasodilatory) or pulmonary function were seen between the two groups.
However, Neukamm said that compared to placebo, rosuvastatin therapy was associated with a significant reduction in hsCRP (p=0.017) and significantly attenuated the rise in IL6 (p=0.028) suggesting reduced systemic inflammation.
One questioner in the audience noted that the placebo group got worse with respect to markers of inflammation during the trial and suggested that this skewed the results in favor of the active treatment. He asked why these increased in placebo patients. Neukamm said the rosuvastatin group did indicate a relative improvement in inflammatory indicators but couldn’t explain the worsening in the placebo patients. There were more current smokers in the placebo group (p<0.05).
Another questioner observed that the changes were very small and also that the lipid parameters were in the normal range. This would tend to lead to overall negative results. Neukamm replied that these patients had a low cardiovascular risk being highly selected to exclude known cardiovascular disease.
Another questioner said IL6 is a very sensitive inflammatory indicator and asked whether that was the reason for difference in placebo results. Neukamm replied that disease progression is associated with a rise in IL6 and this is linked to smoking.