Article Text

Download PDFPDF
Do beta-blockers and inhibitors of the renin–angiotensin aldosterone system improve outcomes in patients with heart failure and left ventricular ejection fraction >40%?
  1. R Thomas Lumbers1,2,3,
  2. Nicole Martin1,
  3. Karthick Manoharan4,
  4. James Thomas5,
  5. L Ceri Davies3
  1. 1 Institute of Health Informatics, University College London, London, UK
  2. 2 Health Data Research UK, London, UK
  3. 3 Barts Heart Centre, St. Bartholomew’s Hospital, London, UK
  4. 4 Department of Cardiology, Royal Surrey County Hospital NHS Foundation Trust, Guildford, Surrey, UK
  5. 5 EPPI-Centre, University College London, London, UK
  1. Correspondence to Dr R Thomas Lumbers, Institute of Health Informatics, University College London, London WC1E 6BT, UK; t.lumbers{at}

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.


Approximately half of all patients with heart failure have preserved left ventricular ejection fraction (LVEF), yet in contrast to heart failure with reduced ejection fraction (HFrEF), no treatments have yet been shown to be effective at improving outcomes.1 Neurohumoral activation is observed in heart failure across the full spectrum of left ventricular function2; however, pharmacological inhibition of the renin–angiotensin aldosterone system (RAAS) has only been shown to improve survival and reduce hospitalisation in HFrEF.1 We therefore performed a Cochrane systematic review and meta-analysis to synthesize all available evidence to investigate the effects of RAAS inhibition in heart failure patients with a LVEF >40%. This patient population comprises both heart failure with mid-range ejection fraction (40%–49%) and heart   failure with preserved ejection fraction (HFpEF, >50%), as defined in current guidelines1.


We searched for randomised controlled trials (RCTs) investigating pharmacological neurohumoral inhibition with beta-blockers (BB), ACE inhibitors (ACEI), angiotensin receptor blockers (ARB), mineralocorticoid receptor antagonists (MRA) and angiotensin receptor–neprilysin inhibitors, in adult patients (≥ 18  years  old) with heart failure and LVEF >40%. We searched MEDLINE, Embase and the Cochrane Central Register of Controlled Trials on 25 July 2017. The primary outcomes were cardiovascular (CV) mortality, heart failure hospitalisation and hyperkalaemia; and the secondary outcomes were all-cause mortality, quality of life (measured using either the Minnesota Living with Heart Failure (MLHF) Questionnaire or Kansas City Cardiomyopathy Questionnaire). We undertook meta-analysis for each drug class and outcome. when data were available from more than one clinical trial. We used a fixed-effect model unless heterogeneity was high (I²≥50%) when a random-effect model was used. We assessed the quality of evidence for each comparison using the GRADE (Grading of Recommendations, Assessment, Development and Evaluations) methodology. The review was conducted in accordance with the guidelines provided in the Cochrane Handbook,3 and reported findings …

View Full Text


  • Contributors RTL wrote the manuscript. NM, KM, JM and CD reviewed the manuscript and approved for submission.

  • Funding This study was supported by an NIHR Cochrane Incentive Award (16/21/19). RTL was supported by an NIHR Clinical Lectureship (CL-2014-18-007) and subsequently by a UKRI Rutherford Fellowship hosted by Health Data Research UK (MR/S003754/1).

  • Competing interests CD has received sponsorship from Servier, Roche and Novartis to attend cardiology conferences, payment from GE Healthcare to give lectures on heart failure and has served as a paid consultant to Servier and Vifor. RTL has received research grants from Pfizer and has served as an unpaid consultant to GSK.

  • Provenance and peer review Commissioned; internally peer reviewed.

  • Patient consent for publication Not required.