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

J Am Coll Cardiol. 2010 May 18;55(20):2201-9. doi: 10.1016/j.jacc.2009.08.091.

Abstract

Objectives: 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).

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Acetylcysteine / administration & dosage*
  • Acute Kidney Injury / chemically induced*
  • Acute Kidney Injury / prevention & control*
  • Aged
  • Angioplasty, Balloon, Coronary
  • Contrast Media / adverse effects*
  • Creatinine / blood
  • Female
  • Free Radical Scavengers / administration & dosage*
  • Humans
  • Logistic Models
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Myocardial Infarction / therapy
  • Myocardial Reperfusion Injury / prevention & control*
  • Oxidative Stress / drug effects
  • Prospective Studies
  • Single-Blind Method
  • Treatment Outcome

Substances

  • Contrast Media
  • Free Radical Scavengers
  • Creatinine
  • Acetylcysteine

Associated data

  • ClinicalTrials.gov/NCT00463749