title: A prospective, double-blind, randomized controlled trial of the angiotensin-converting enzyme inhibitor Ramipril In Aortic Stenosis (RIAS trial).
abstract: OBJECTIVE
  Angiotensin-converting enzyme (ACE) inhibitors improve left ventricular (LV) remodelling and outcome in heart failure and hypertensive heart disease. They may be similarly beneficial in patients with aortic stenosis (AS), but historical safety concerns have limited their use, and no prospective clinical trials exist.
  
  
  RESULTS
  We conducted a prospective, randomized, double-blind, placebo-controlled trial in 100 patients with moderate or severe asymptomatic AS to examine the physiological effects of ramipril, particularly LV mass (LVM) regression. Subjects were randomized to ramipril 10 mg daily (n = 50) or placebo (n = 50) for 1 year, and underwent cardiac magnetic resonance, echocardiography, and exercise testing at 0, 6, and 12 months, with follow-up data available in 77 patients. There was a modest but progressive reduction in LVM (the primary end point) in the ramipril group vs. the placebo group (mean change -3.9 vs. +4.5 g, respectively, P = 0.0057). There were also trends towards improvements in myocardial physiology: the ramipril group showed preserved tissue Doppler systolic velocity compared with placebo (+0.0 vs. -0.5 cm/s, P = 0.04), and a slower rate of progression of the AS (valve area 0.0 cm(2) in the ramipril group vs. -0.2 cm(2) in the placebo arm, P = 0.067). There were no significant differences in major adverse cardiac events.
  
  
  CONCLUSIONS
  ACE inhibition leads to a modest, but progressive reduction in LVM in asymptomatic patients with moderate-severe AS compared with placebo, with trends towards improvements in myocardial physiology and slower progression of valvular stenosis. A larger clinical outcome trial to confirm these findings and explore their clinical relevance is required.
authors: University of Oxford Centre for Clinical Magnetic Resonance Research (OCMR), Division of Cardiovascular Medicine, Radcliffe Department of Medicine, John Radcliffe Hospital, Headley Way, Headington, Oxford OX3 9DU, UK.
authors: Sacha
authors: S
authors: Bull
authors: University of Oxford Centre for Clinical Magnetic Resonance Research (OCMR), Division of Cardiovascular Medicine, Radcliffe Department of Medicine, John Radcliffe Hospital, Headley Way, Headington, Oxford OX3 9DU, UK.
authors: Margaret
authors: M
authors: Loudon
authors: University of Oxford Centre for Clinical Magnetic Resonance Research (OCMR), Division of Cardiovascular Medicine, Radcliffe Department of Medicine, John Radcliffe Hospital, Headley Way, Headington, Oxford OX3 9DU, UK.
authors: Jane M
authors: JM
authors: Francis
authors: University of Oxford Centre for Clinical Magnetic Resonance Research (OCMR), Division of Cardiovascular Medicine, Radcliffe Department of Medicine, John Radcliffe Hospital, Headley Way, Headington, Oxford OX3 9DU, UK.
authors: Jubin
authors: J
authors: Joseph
authors: Centre for Statistics in Medicine, University of Oxford, Nuffield Orthopaedic Centre, Oxford OX3 7LD, UK.
authors: Stephen
authors: S
authors: Gerry
authors: University of Oxford Centre for Clinical Magnetic Resonance Research (OCMR), Division of Cardiovascular Medicine, Radcliffe Department of Medicine, John Radcliffe Hospital, Headley Way, Headington, Oxford OX3 9DU, UK.
authors: Theodoros D
authors: TD
authors: Karamitsos
authors: Department of Cardiology, Oxford Heart Centre, John Radcliffe Hospital, Oxford OX3 9DU, UK.
authors: Bernard D
authors: BD
authors: Prendergast
authors: Department of Cardiology, Oxford Heart Centre, John Radcliffe Hospital, Oxford OX3 9DU, UK.
authors: Adrian P
authors: AP
authors: Banning
authors: University of Oxford Centre for Clinical Magnetic Resonance Research (OCMR), Division of Cardiovascular Medicine, Radcliffe Department of Medicine, John Radcliffe Hospital, Headley Way, Headington, Oxford OX3 9DU, UK.
authors: Stefan
authors: S
authors: Neubauer
authors: University of Oxford Centre for Clinical Magnetic Resonance Research (OCMR), Division of Cardiovascular Medicine, Radcliffe Department of Medicine, John Radcliffe Hospital, Headley Way, Headington, Oxford OX3 9DU, UK Department of Cardiology, Oxford Heart Centre, John Radcliffe Hospital, Oxford OX3 9DU, UK saul.myerson@cardiov.ox.ac.uk.
authors: Saul G
authors: SG
authors: Myerson
mesh_terms: D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D001024:Aortic Valve Stenosis / Q000188:drug therapy*; D018450:Disease Progression; D004311:Double-Blind Method; D004452:Echocardiography; D004562:Electrocardiography; D005080:Exercise Test; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D011446:Prospective Studies; D017257:Ramipril / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D017257:Ramipril
keywords: ACE inhibition; aortic stenosis; myocardium; valve disease