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

Douglas Greig, Hernan Alcaino, Pablo F. Castro, Lorena Garcia, Hugo E. Verdejo, Mario Navarro, Rafael Lpez, Rosemarie Mellado, Fabiola Tapia, Luigi A. Gabrielli, Camilo Nogerol, Mario Chiong, Ivan Godoy, Sergio Lavandero

Research output: Contribution to journalArticlepeer-review

26 Citations (Scopus)

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 μmol/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.

Original languageEnglish
Pages (from-to)408-413
Number of pages6
JournalJournal of Heart and Lung Transplantation
Volume30
Issue number4
DOIs
Publication statusPublished - 1 Apr 2011

Keywords

  • allopurinol
  • endothelial dysfunction
  • heart failure
  • oxidative stress
  • statins

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine
  • Transplantation

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