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Controlled release metoprolol for aortic regurgitation: a randomised clinical trial
  1. Kaspar Broch1,2,
  2. Stig Urheim1,3,
  3. Mai Tone Lønnebakken4,5,
  4. Wenche Stueflotten1,
  5. Richard Massey1,
  6. Kristian Fosså6,
  7. Einar Hopp6,
  8. Svend Aakhus1,
  9. Lars Gullestad1,2
  1. 1Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway
  2. 2Faculty of Medicine, K. G. Jebsen Cardiac Research Centre and Center for Heart Failure Research, University of Oslo, Oslo, Norway
  3. 3Institute for Surgical Research, Oslo University Hospital Rikshospitalet, Oslo, Norway
  4. 4Department of Clinical Science, University of Bergen, Bergen, Norway
  5. 5Department of Heart Disease, Haukeland University Hospital, Bergen, Norway
  6. 6Department of Radiology and Nuclear Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway
  1. Correspondence to Dr Kaspar Broch, Department of Cardiology, Oslo University Hospital, Rikshospitalet, Oslo 0027, Norway; kaspar.broch{at}


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. β-adrenergic receptor antagonists (β-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.

Trial registration number Identifier: NCT01157572-results.

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