PMID- 21145258
OWN - NLM
STAT- MEDLINE
DCOM- 20110818
LR  - 20220317
IS  - 1557-3117 (Electronic)
IS  - 1053-2498 (Linking)
VI  - 30
IP  - 4
DP  - 2011 Apr
TI  - Xanthine-oxidase inhibitors and statins in chronic heart failure: effects on 
      vascular and functional parameters.
PG  - 408-13
LID - 10.1016/j.healun.2010.10.003 [doi]
AB  - 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 mumol/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 strengthened by the addition of allopurinol.
CI  - Copyright (c) 2011 International Society of Heart and Lung Transplantation. 
      Published by Elsevier Inc. All rights reserved.
FAU - Greig, Douglas
AU  - Greig D
AD  - Departamento de Enfermedades Cardiovasculares, Facultad de Medicina, P. 
      Universidad Catolica de Chile, Santiago, Chile. dgreig@puc.cl
FAU - Alcaino, Hernan
AU  - Alcaino H
FAU - Castro, Pablo F
AU  - Castro PF
FAU - Garcia, Lorena
AU  - Garcia L
FAU - Verdejo, Hugo E
AU  - Verdejo HE
FAU - Navarro, Mario
AU  - Navarro M
FAU - Lopez, Rafael
AU  - Lopez R
FAU - Mellado, Rosemarie
AU  - Mellado R
FAU - Tapia, Fabiola
AU  - Tapia F
FAU - Gabrielli, Luigi A
AU  - Gabrielli LA
FAU - Nogerol, Camilo
AU  - Nogerol C
FAU - Chiong, Mario
AU  - Chiong M
FAU - Godoy, Ivan
AU  - Godoy I
FAU - Lavandero, Sergio
AU  - Lavandero S
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20101208
PL  - United States
TA  - J Heart Lung Transplant
JT  - The Journal of heart and lung transplantation : the official publication of the 
      International Society for Heart Transplantation
JID - 9102703
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Heptanoic Acids)
RN  - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors)
RN  - 0 (Pyrroles)
RN  - 63CZ7GJN5I (Allopurinol)
RN  - A0JWA85V8F (Atorvastatin)
RN  - EC 1.17.3.2 (Xanthine Oxidase)
SB  - IM
MH  - Allopurinol/administration & dosage
MH  - Atorvastatin
MH  - Double-Blind Method
MH  - Endothelium, Vascular/*drug effects/physiopathology
MH  - Enzyme Inhibitors/*administration & dosage
MH  - Female
MH  - Heart Failure/*drug therapy/physiopathology
MH  - Heptanoic Acids/administration & dosage
MH  - Humans
MH  - Hydroxymethylglutaryl-CoA Reductase Inhibitors/*administration & dosage
MH  - Male
MH  - Middle Aged
MH  - Oxidative Stress/drug effects
MH  - Pyrroles/administration & dosage
MH  - Regional Blood Flow/drug effects
MH  - Treatment Outcome
MH  - Xanthine Oxidase/antagonists & inhibitors
EDAT- 2010/12/15 06:00
MHDA- 2011/08/19 06:00
CRDT- 2010/12/15 06:00
PHST- 2010/06/23 00:00 [received]
PHST- 2010/10/21 00:00 [revised]
PHST- 2010/10/22 00:00 [accepted]
PHST- 2010/12/15 06:00 [entrez]
PHST- 2010/12/15 06:00 [pubmed]
PHST- 2011/08/19 06:00 [medline]
AID - S1053-2498(10)00672-8 [pii]
AID - 10.1016/j.healun.2010.10.003 [doi]
PST - ppublish
SO  - J Heart Lung Transplant. 2011 Apr;30(4):408-13. doi: 
      10.1016/j.healun.2010.10.003. Epub 2010 Dec 8.