title: Effects of alagebrium, an advanced glycation endproduct breaker, on exercise tolerance and cardiac function in patients with chronic heart failure.
abstract: OBJECTIVE
  Advanced glycation endproducts (AGEs) have been associated with the development and progression of chronic heart failure (CHF). Advanced glycation endproducts-crosslink breakers might be of benefit in HF, but only small-scale and uncontrolled data are available. Our aim was to conduct a prospective, randomized, double-blind, placebo-controlled study to examine the effects of the AGE-breaker alagebrium on exercise capacity and cardiac function in patients with HF.
  
  
  RESULTS
  One hundred and two patients with HF (78% male, aged 62 ± 11 years), and a left ventricular ejection fraction (LVEF) ≤0.45, were randomized to either 200 mg alagebrium twice daily or placebo. After 36 weeks, the primary efficacy end-point peak VO(2) had changed by (mean ± SEM) -2.1 ± 0.5 mL/min/kg in alagebrium vs. -0.5 ± 0.7 mL/min/kg in placebo-treated patients (P= 0.06). No significant changes were observed in a number of secondary end-points, including diastolic function (mean E': P= 0.32; E/E': P= 0.81), systolic function (LVEF: P= 0.43), AGE accumulation (skin-autofluorescence: P= 0.42), N-terminal pro brain natriuretic peptide, P= 0.20); New York Heart Association functional class (P= 0.73), patient global assessment (P= 0.32), physicians global assessment (P= 0.76), and the Minnesota Living with Heart Failure Questionnaire score (P= 0.38). Overall alagebrium was reasonably well tolerated.
  
  
  CONCLUSIONS
  In the present proof-of-concept study, the AGE-breaker alagebrium did not improve exercise tolerance in patients with HF and systolic dysfunction, and no changes were observed in a number of secondary endpoints. The present data therefore do not support earlier data which suggested a beneficial effect of alagebrium in systolic HF.
  
  
  BACKGROUND
  NCT00516646 (http://clinicaltrials.gov).
authors.affiliation: Department of Cardiology, University Medical Center Groningen, University of Groningen, PO Box 30.001, 9700 RB, Groningen, The Netherlands.
authors.forename: Jasper W L
authors.initials: JW
authors.lastname: Hartog
authors.forename: Suzan
authors.initials: S
authors.lastname: Willemsen
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: van Veldhuisen
authors.forename: Jan L
authors.initials: JL
authors.lastname: Posma
authors.forename: Leen M
authors.initials: LM
authors.lastname: van Wijk
authors.forename: Yoran M
authors.initials: YM
authors.lastname: Hummel
authors.forename: Hans L
authors.initials: HL
authors.lastname: Hillege
authors.forename: Adriaan A
authors.initials: AA
authors.lastname: Voors
mesh_terms: D000368:Aged; D002317:Cardiovascular Agents / Q000627:therapeutic use*; D002908:Chronic Disease; D003935:Diagnostic Techniques, Cardiovascular; D004311:Double-Blind Method; D017079:Exercise Tolerance / Q000187:drug effects*; D005260:Female; D017127:Glycation End Products, Advanced / Q000037:antagonists & inhibitors*; D006333:Heart Failure / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013844:Thiazoles / Q000627:therapeutic use*
chemical_list: D002317:Cardiovascular Agents; D017127:Glycation End Products, Advanced; D013844:Thiazoles; C406794:alagebrium