title: Impact of high-dose N-acetylcysteine versus placebo on contrast-induced nephropathy and myocardial reperfusion injury in unselected patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention. The LIPSIA-N-ACC (Prospective, Single-Blind, Placebo-Controlled, Randomized Leipzig Immediate PercutaneouS Coronary Intervention Acute Myocardial Infarction N-ACC) Trial.
abstract: OBJECTIVE
  The aim of this randomized, single-blind, controlled trial was to assess N-acetylcysteine effects on contrast-induced nephropathy and reperfusion injury in ST-segment elevation myocardial infarction patients undergoing primary angioplasty with moderate contrast volumes.
  
  
  BACKGROUND
  High-dose N-acetylcysteine reduced the incidence of contrast-induced nephropathy in patients with high contrast volumes and reduced reperfusion injury in animal trials.
  
  
  METHODS
  Patients undergoing primary angioplasty were randomized to either high-dose N-acetylcysteine (2 x 1,200 mg/day for 48 h; n = 126) or placebo plus optimal hydration (n = 125). The 2 primary end points were: 1) the occurrence of >25% increase in serum creatinine level <72 h after randomization; and 2) a reduction in reperfusion injury measured as myocardial salvage index by magnetic resonance imaging.
  
  
  RESULTS
  The median volume of an iso-osmolar contrast agent during angiography was 180 ml (interquartile range [IQR] 140 to 230 ml) in the N-acetylcysteine and 160 ml (IQR 120 to 220 ml) in the placebo group (p = 0.20). The primary end point contrast-induced nephropathy occurred in 14% of the N-acetylcysteine group and in 20% of the placebo group (p = 0.28). The myocardial salvage index was also not different between both treatment groups (43.5; IQR 25.4 to 71.9 vs. 51.5; IQR 29.5 to 75.3; p = 0.36). Activated oxygen protein products and oxidized low-density lipoprotein as markers for oxidative stress were reduced by as much as 20% in the N-acetylcysteine group (p < 0.05), whereas no change was evident in the placebo group.
  
  
  CONCLUSIONS
  High-dose intravenous N-acetylcysteine reduces oxidative stress. However, it does not provide an additional clinical benefit to placebo with respect to CIN and myocardial reperfusion injury in nonselected patients undergoing angioplasty with moderate doses of contrast medium and optimal hydration. (Myocardial Salvage and Contrast Dye Induced Nephropathy Reduction by N-Acetylcysteine [LIPSIA-N-ACC]; NCT00463749).
authors.affiliation: Department of Internal Medicine-Cardiology, University of Leipzig Heart Center, Leipzig, Germany. thielh@medizin.uni-leipzig.de
authors.forename: Holger
authors.initials: H
authors.lastname: Thiele
authors.forename: Lysann
authors.initials: L
authors.lastname: Hildebrand
authors.forename: Carmen
authors.initials: C
authors.lastname: Schirdewahn
authors.forename: Ingo
authors.initials: I
authors.lastname: Eitel
authors.forename: Volker
authors.initials: V
authors.lastname: Adams
authors.forename: Georg
authors.initials: G
authors.lastname: Fuernau
authors.forename: Sandra
authors.initials: S
authors.lastname: Erbs
authors.forename: Axel
authors.initials: A
authors.lastname: Linke
authors.forename: Klaus-Werner
authors.initials: KW
authors.lastname: Diederich
authors.forename: Marek
authors.initials: M
authors.lastname: Nowak
authors.forename: Steffen
authors.initials: S
authors.lastname: Desch
authors.forename: Matthias
authors.initials: M
authors.lastname: Gutberlet
authors.forename: Gerhard
authors.initials: G
authors.lastname: Schuler
mesh_terms: D000111:Acetylcysteine / Q000008:administration & dosage*; D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000517:prevention & control*; D000368:Aged; D015906:Angioplasty, Balloon, Coronary; D003287:Contrast Media / Q000009:adverse effects*; D003404:Creatinine / Q000097:blood; D005260:Female; D016166:Free Radical Scavengers / Q000008:administration & dosage*; D006801:Humans; D016015:Logistic Models; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000628:therapy; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D018384:Oxidative Stress / Q000187:drug effects; D011446:Prospective Studies; D016037:Single-Blind Method; D016896:Treatment Outcome
chemical_list: D003287:Contrast Media; D016166:Free Radical Scavengers; D003404:Creatinine; D000111:Acetylcysteine