Xanthine-oxidase inhibitors and statins in chronic heart failure: Effects on vascular and functional parameters

Abstract

BACKGROUND: Increased oxidative stress in heart failure (HF) leads to inflammation and endothelial dysfunction (ED). Both statins and allopurinol have known anti-oxidant properties, but their utility in HF has not been fully assessed.

METHODS: This investigation was a prospective, double-blind, double-dummy study, performed between March 2007 and June 2009. Seventy-four HF patients, with New York Heart Association (NYHA) Class II or III status and left ventricular ejection fraction (LVEF) <40%, were included. Patients received placebo during 4 weeks and were then randomized to receive 4 weeks of either atorvastatin 20 mg/day plus placebo (ATV+PLA group) or atorvastatin 20 mg/day orally plus allopurinol 300 mg/day orally (ATV +ALLO group). Malondialdehyde (MDA), extracellular superoxide dismutase (ecSOD) activity and uric acid (UA) levels, among others, were determined at baseline and after 4 weeks of treatment. ED was assessed by flow-dependent endothelial-mediated vasodilation (FDD), and functional capacity by 6-minute walk test (6MWT).

RESULTS: Thirty-two patients were randomized to ATV+PLA and 38 to ATV+ALLO. Mean age was 59 +/- 2 years, 82% were male, and 22% had an ischemic etiology. Hypertension was present in 60% and diabetes in 15% of those studied. No significant differences were observed between baseline measurements and after placebo. After 4 weeks of treatment, both groups showed a significant decrease on MDA (0.9 +/- 0.1 to 0.8 +/- 0.1 and 1.0 +/- 0.5 to 0.9 +/- 0.1 mu mol/liter, p = 0.88), UA (7.4 +/- 0.4 to 6.8 +/- 0.3 and 7.2 +/- 0.4 to 5.0 +/- 0.3 mg/dl, p <0.01) and FDD (3.9 +/- 0.2% to 5.6 +/- 0.4% and 4.6 +/- 0.3% to 7.1 +/- 0.5%, p = 0.07) with increased ecSOD activity (109 +/- 11 to 173 +/- 13 and 98 +/- 10 to 202 +/- 16. U/ml/min, p = 0.41) and improved 6MWT (447 +/- 18 to 487 +/- 19 and 438 +/- 17 to 481 +/- 21 m, p = 0.83), with all values for ATV +PLA and ATV+ALLO, respectively; p-values are for comparison between groups after treatment.

CONCLUSION: Short-term ATV treatment in heart failure (HF) patients reduces oxidative stress and improves FDD and functional capacity. These beneficial effects are not strenghthened by the addition of alopurinol. J Heart Lung Transplant 2011;30:408-13 (C) 2011 International Society of Heart and Lung Transplantation. All rights reserved.