title: Effect of restrictive versus liberal transfusion strategies on outcomes in patients with cardiovascular disease in a non-cardiac surgery setting: systematic review and meta-analysis.
abstract: OBJECTIVE
  To compare patient outcomes of restrictive versus liberal blood transfusion strategies in patients with cardiovascular disease not undergoing cardiac surgery.
  
  
  METHODS
  Systematic review and meta-analysis.
  
  
  METHODS
  Randomised controlled trials involving a threshold for red blood cell transfusion in hospital. We searched (to 2 November 2015) CENTRAL, Medline, Embase, CINAHL, PubMed, LILACS, NHSBT Transfusion Evidence Library, ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, ISRCTN Register, and EU Clinical Trials Register. Authors were contacted for data whenever possible.
  Published and unpublished randomised controlled trials comparing a restrictive with liberal transfusion threshold and that included patients with cardiovascular disease.
  
  
  METHODS
  Data extraction was completed in duplicate. Risk of bias was assessed using Cochrane methods. Relative risk ratios with 95% confidence intervals were presented in all meta-analyses. Mantel-Haenszel random effects models were used to pool risk ratios.
  
  
  METHODS
  30 day mortality, and cardiovascular events.
  
  
  RESULTS
  41 trials were identified; of these, seven included data on patients with cardiovascular disease. Data from a further four trials enrolling patients with cardiovascular disease were obtained from the authors. In total, 11 trials enrolling patients with cardiovascular disease (n=3033) were included for meta-analysis (restrictive transfusion, n=1514 patients; liberal transfusion, n=1519). The pooled risk ratio for the association between transfusion thresholds and 30 day mortality was 1.15 (95% confidence interval 0.88 to 1.50, P=0.50), with little heterogeneity (I(2)=14%). The risk of acute coronary syndrome in patients managed with restrictive compared with liberal transfusion was increased (nine trials; risk ratio 1.78, 95% confidence interval 1.18 to 2.70, P=0.01, I(2)=0%).
  
  
  CONCLUSIONS
  The results show that it may not be safe to use a restrictive transfusion threshold of less than 80 g/L in patients with ongoing acute coronary syndrome or chronic cardiovascular disease. Effects on mortality and other outcomes are uncertain. These data support the use of a more liberal transfusion threshold (>80 g/L) for patients with both acute and chronic cardiovascular disease until adequately powered high quality randomised trials have been undertaken in patients with cardiovascular disease.
  
  
  BACKGROUND
  PROSPERO CRD42014014251.
authors.affiliation: Centre for Inflammation Research, University of Edinburgh, Edinburgh, UK Critical Care Department, Royal Infirmary Edinburgh, Edinburgh, UK annemarie.docherty@ed.ac.uk.
authors.forename: Annemarie B
authors.initials: AB
authors.lastname: Docherty
authors.affiliation: Critical Care Department, Royal Infirmary Edinburgh, Edinburgh, UK.
authors.forename: Rob
authors.initials: R
authors.lastname: O'Donnell
authors.affiliation: Systematic Review Initiative, NHS Blood and Transplant, John Radcliffe Hospital, Oxford, UK.
authors.forename: Susan
authors.initials: S
authors.lastname: Brunskill
authors.affiliation: Systematic Review Initiative, NHS Blood and Transplant, John Radcliffe Hospital, Oxford, UK.
authors.forename: Marialena
authors.initials: M
authors.lastname: Trivella
authors.affiliation: Centre for Statistics in Medicine, University of Oxford, Oxford, UK.
authors.forename: Carolyn
authors.initials: C
authors.lastname: Doree
authors.affiliation: Department of Intensive Care, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Lars
authors.initials: L
authors.lastname: Holst
authors.affiliation: Department of Orthopaedics, Peterborough and Stamford Hospitals NHS Trust, Peterborough, UK.
authors.forename: Martyn
authors.initials: M
authors.lastname: Parker
authors.affiliation: Department of Geriatrics, Aarhus University, Aarhus, Denmark.
authors.forename: Merete
authors.initials: M
authors.lastname: Gregersen
authors.affiliation: Surgical Intensive Care Unit and Department of Anesthesiology, Cancer Institute, Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, Brazil.
authors.forename: Juliano
authors.initials: J
authors.lastname: Pinheiro de Almeida
authors.affiliation: Centre for Inflammation Research, University of Edinburgh, Edinburgh, UK Critical Care Department, Royal Infirmary Edinburgh, Edinburgh, UK.
authors.forename: Timothy S
authors.initials: TS
authors.lastname: Walsh
authors.affiliation: Systematic Review Initiative, NHS Blood and Transplant, John Radcliffe Hospital, Oxford, UK Department of Haematology, NHS Blood and Transplant/Oxford University Hospitals NHS Trust, Oxford, UK.
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Stanworth
mesh_terms: D054058:Acute Coronary Syndrome / Q000209:etiology / Q000401:mortality; D000328:Adult; D001803:Blood Transfusion / Q000379:methods* / Q000401:mortality; D002318:Cardiovascular Diseases / Q000150:complications* / Q000401:mortality; D006801:Humans; D011183:Postoperative Complications / Q000209:etiology / Q000401:mortality; D016032:Randomized Controlled Trials as Topic; D013514:Surgical Procedures, Operative / Q000379:methods* / Q000401:mortality; D016896:Treatment Outcome