Effects of alagebrium, an advanced glycation endproduct breaker, on exercise tolerance and cardiac function in patients with chronic heart failure

Aims 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. Methods and 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 VO2 had changed by (mean +/- SEM) 22.1 +/- 0.5 mL/min/kg in alagebrium vs. 20.5 +/- 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. Conclusion 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. Clinical Trial Registration Information: NCT00516646 (http://clinicaltrials.gov)