title: 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 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.
  
  
  CONCLUSIONS
  Short-term ATV treatment in heart failure (HF) patients reduces oxidative stress and improves FDD and functional capacity. These beneficial effects are not strengthened by the addition of allopurinol.
authors.affiliation: Departamento de Enfermedades Cardiovasculares, Facultad de Medicina, P. Universidad Católica de Chile, Santiago, Chile. dgreig@puc.cl
authors.forename: Douglas
authors.initials: D
authors.lastname: Greig
authors.forename: Hernan
authors.initials: H
authors.lastname: Alcaino
authors.forename: Pablo F
authors.initials: PF
authors.lastname: Castro
authors.forename: Lorena
authors.initials: L
authors.lastname: Garcia
authors.forename: Hugo E
authors.initials: HE
authors.lastname: Verdejo
authors.forename: Mario
authors.initials: M
authors.lastname: Navarro
authors.forename: Rafael
authors.initials: R
authors.lastname: López
authors.forename: Rosemarie
authors.initials: R
authors.lastname: Mellado
authors.forename: Fabiola
authors.initials: F
authors.lastname: Tapia
authors.forename: Luigi A
authors.initials: LA
authors.lastname: Gabrielli
authors.forename: Camilo
authors.initials: C
authors.lastname: Nogerol
authors.forename: Mario
authors.initials: M
authors.lastname: Chiong
authors.forename: Ivan
authors.initials: I
authors.lastname: Godoy
authors.forename: Sergio
authors.initials: S
authors.lastname: Lavandero
mesh_terms: D000493:Allopurinol / Q000008:administration & dosage; D000069059:Atorvastatin; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000008:administration & dosage*; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006538:Heptanoic Acids / Q000008:administration & dosage; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects; D011758:Pyrroles / Q000008:administration & dosage; D012039:Regional Blood Flow / Q000187:drug effects; D016896:Treatment Outcome; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors
chemical_list: D004791:Enzyme Inhibitors; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D000493:Allopurinol; D000069059:Atorvastatin; D014969:Xanthine Oxidase