Effects of simvastatin in chronic obstructive pulmonary disease: Results of a pilot, randomized, placebo-controlled clinical trial

Abstract

Introduction: Statins may have pleiotropic effects in COPD, but mechanisms remain unclear.

Objectives: To assess the pleiotropic effect of statins in patients with stable COPD on (1): lung function (2); pulmonary and systemic inflammation (3); endothelial function (vascular stiffness) and circulating vascular growth factors; and (4), serum uric acid levels.

Method: Pilot, double-blind, randomized, placebo-controlled clinical trial in 24 patients with stable COPD, all statin-naïve, who were randomized (1:1) to receive simvastatin 40 mg/24 h during 12 weeks (n = 12; 69.0 ± 7.3 years; post-bd FEV₁ 53.4 ± 10.0% pred.) or placebo (n = 12; 66.4 ± 4.6 years; post-bd FEV₁ 48.2 ± 12.6% pred.). Nine patients per group (total n = 18) completed the study.

Results: Lung function, pulmonary and systemic inflammatory markers and the degree of vascular stiffness did not change significantly in any group. However, treatment with simvastatin increased the plasma levels of erythropoietin (Epo) (4.2 ± 2.2 mIU/mL to 6.8 ± 3.2 mlU/mL, p < 0.05) and reduced those of serum uric acid (7.1 ± 1.3 mg/dL to 6.5 ± 1.4 mg/dL, p < 0.01).

Conclusions: Short-term treatment with simvastatin in stable COPD patients did not modify lung function, pulmonary and systemic inflammation, or vascular stiffness, but it changed Epo and uric acid levels.

Keywords: COPD; Erythropoietin; Inflammation; Statins; Uric acid.

Fig. 1

CONSORT flowchart diagram of the trial. For further explanations, see text.

Fig. 2

Mean values (±SD) of circulating levels of uric acid and erythropoietin in COPD patients treated with simvastatin (black bars) and in the placebo group (white bars). Simvastatin reduces (p < 0.01) serum uric acid levels (A), while raising (p < 0.05) the erythropoietin plasma levels (B). No changes were observed in placebo group (A and B).