Controlled release metoprolol for aortic regurgitation: a randomised clinical trial

Objective Chronic aortic regurgitation (AR) creates a volume load on the left ventricle, which induces adaptive responses. With time, excessive left ventricular (LV) dilatation may precipitate heart failure. beta-adrenergic receptor antagonists (beta-blockers) are beneficial in patients with heart failure, but their effect in AR is unclear. This trial was designed to evaluate the effect of controlled release metoprolol on LV remodelling in patients with AR. Methods In this double blind trial, 75 asymptomatic patients aged 44 +/- 14 years, 89% males, fulfilling at least two echocardiographic criteria for moderate or severe chronic AR, were randomised to receive metoprolol CR/XL up-titrated to 200 mg/day, or matching placebo. The primary endpoint was LV end diastolic volume, measured by MRI after 6 months of treatment. Results After 6 months, the difference in the baseline-adjusted LV end diastolic volume between patients allocated to metoprolol and those allocated to placebo was 8 (95% CI -8 to 25) mL (p=0.32). The adjusted LV ejection fraction was 2.7 (95% CI 0.1 to 5.3) percentage points higher in the metoprolol group than in the placebo group (p=0.04). The exercise capacity and peak oxygen consumption did not differ between treatment arms. Serum concentrations of N-terminal pro-B-type natriuretic peptide were 138 (95% CI 71 to 205) pg/mL higher in the metoprolol group (p < 0.001). There were no serious adverse events in either treatment arm. Conclusions Treatment with metoprolol of adults with chronic, moderate to severe AR had no effect on LV volumes.