Dual Renin-Angiotensin System Blockade for Patients With Prosthesis-Patient Mismatch

Abstract

Patients with prosthesis-patient mismatch (PPM) continue to show some degrees of left ventricular hypertrophy after aortic valve replacement for aortic stenosis. The renin-angiotensin system plays a major role in promoting and sustaining hypertrophy. In a controlled, randomized study, we tested the hypothesis that the combination of angiotensin-converting enzyme inhibitors (ACEi) plus angiotensin II receptor blocker (ARB) can be more effective in decreasing hypertrophy than a largely employed association such as ACEi plus ß-blockers in PPM patients. We enrolled a total of 72 patients with aortic valve replacement and evidence of PPM (effective orifice area <0.85 cm(2)/m(2)) at postoperative echocardiography. At discharge, they were randomly assigned to ramipril plus candesartan (n = 36) or ramipril plus metoprolol (n = 36). At baseline, age, 24-hour blood pressure, left ventricular measurements, and transprosthetic gradients were similar between the two groups. After 12 months, the extent of 24-hour systolic and diastolic blood pressure decrease was similar between the two groups (-13.3% and 16.3% versus -12.3% and 15.8%, respectively; p = 0.7 and 0.8, respectively). Left ventricular mass index significantly decreased in both groups (ACEi plus ARB 165 ± 19 g/m(2) to 117 ± 17 g/m(2); p < 0.0001; ACEi plus β-blockers 161 ± 15 g/m(2) to 128 ± 20 g/m(2); p < 0.0001). However, patients receiving ACEi plus ARB had a higher decrease of left ventricular mass (-46 ± 15 g/m(2) versus -35 ± 12 g/m(2); p = 0.001) and a lower rate of residual left ventricular hypertrophy (22% versus 47%; p = 0.04). This study shows that in patients with PPM, the association ACEi and ARB has a greater antiremodeling effect compared with ACEi and β-blockers, and is independent of blood pressure.