Abstract 20766: Direct Renin Inhibition With Aliskiren Promotes Left Ventricular Reverse Remodelling After Coronary Artery Bypass Grafting
Background: After myocardial infarction, left ventricular (LV) remodelling is associated with poorer outcome. Coronary artery bypass grafting (CABG) is expected to induce a reverse remodelling but this process lacks to be observed in most patients. The renin-angiotensin system (RAS) plays and important role in promoting LV remodelling in ischemic heart failure and angiotensin converting enzyme (ACE) inhibitors are usually adopted as standard medical therapy. Aliskiren, the first orally active direct renin inhibitor, represents a novel approach to RAS suppression by directly inhibiting the system at the rate-limiting proximal step. In a controlled, randomized study, we tested the hypothesis that aliskiren can be more effective in promoting LV reverse remodelling than ACE inhibition after CABG.
Methods and Results: Among 956 patient undergoing isolated CABG, we enrolled a total of 84 patients having evidence of LV remodelling (LV systolic volume index>40ml/m2) without relevant mitral regurgitation (<2+) at postoperative echo (within 7 days from surgery). At discharge, they were randomized to ramipril + metoprololo (n=42) or aliskiren + metoprololo (n=42). After the 12-month treatment, they underwent a 24-h blood pressure (BP) monitoring and echocardiographic examination. At baseline, age, 24-h blood pressure and LV morpho-functional parameters were similar between the two groups. All 84 patients completed 12-months follow-up. Aliskiren was associated with a better result in terms of reduction in LV systolic volume index (−15 ±5 ml/m2 versus -9±5 ml/m2 from baseline, P <0.001), LV diastolic volume index (−12 ±5 ml/m2 versus -6±4 ml/m2 from baseline, P = 0.008) and improvement of LV ejection fraction (+8 ±3% versus +2±4% ml/m2 from baseline, P = 0.01). LV reverse remodelling (reduction in LV systolic volume index >15%) was present in 28/42 and 13/42 patients after Aliskiren and Ramipril respectively (p=0.03). The extent of 24-h BP decrease was similar between the two groups (−13.3/16.3% vs. -12.3/15.8%, P = 0.63/P = 0.71)
Conclusions: In comparison with ramipril, aliskiren was associated with a greater degree of LV reverse remodelling after CABG. This effect can be reasonably ascribed to a blood pressure-independent effect of aliskiren.
- © 2010 by American Heart Association, Inc.