Several lines of evidence have suggested that Advanced Glycation End-products (AGEs) play a role in the development and progression of heart failure. The AGE-crosslink breaker Alagebrium (ALT-711) improved cardiac function and symptoms in experimental and small human heart failure studies. These results have not yet been confirmed in a randomized controlled clinical trial.

This study is a double-blind, randomized, placebo-controlled, parallel design trial enrolling 100 patients (2x50) with stable CHF. Patients will be randomized to either 200 mg Alagebrium twice daily or placebo for a period of 9 months. Efficacy measurements will be performed at baseline, and at the end of the study, and include aerobic capacity (VO2max) exercise testing, echocardiography, Minnesota Living with Heart Failure score, AGEs measurements in blood and skin, NYHA heart failure class, patient's and physician's global assessment, and levels of NT-pro-BNP. Safety visits are performed at 3 months intervals. In addition, one safety visit will be performed 2 weeks after the randomization visit and 1 month after the last treatment visit. A total of 8 visits will be performed during the entire study.

Inclusion Criteria:

• NYHA II-IV heart failure
• Echocardiographic ejection fraction ≤ 40%
• Duration of heart failure > 3 months
• Stable heart failure medical therapy for > 1 months

Exclusion Criteria:

• History of myocardial infarction in previous 6 months
• History of stroke in previous 6 months
• Clinically significant renal, liver, pulmonary,or hematological disease
• Active and or treated malignancies within 12 months
• Uncontrolled diabetes mellitus