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 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.
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).