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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

BMJ 2016; 352 doi: (Published 29 March 2016) Cite this as: BMJ 2016;352:i1351
  1. Annemarie B Docherty, specialty registrar, research fellow1 2,
  2. Rob O’Donnell, specialty registrar2,
  3. Susan Brunskill, senior information scientist3,
  4. Marialena Trivella, lecturer3,
  5. Carolyn Doree, information specialist4,
  6. Lars B Holst, medical doctor, research fellow5,
  7. Martyn Parker, consultant orthopaedic surgeon6,
  8. Merete Gregersen, clinical specialist7,
  9. Juliano Pinheiro de Almeida, medical doctor, research fellow8,
  10. Timothy S Walsh, professor of critical care1 2,
  11. Simon J Stanworth, consultant haematologist3 9
  1. 1Centre for Inflammation Research, University of Edinburgh, Edinburgh, UK
  2. 2Critical Care Department, Royal Infirmary Edinburgh, Edinburgh, UK
  3. 3Systematic Review Initiative, NHS Blood and Transplant, John Radcliffe Hospital, Oxford, UK
  4. 4Centre for Statistics in Medicine, University of Oxford, Oxford, UK
  5. 5Department of Intensive Care, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
  6. 6Department of Orthopaedics, Peterborough and Stamford Hospitals NHS Trust, Peterborough, UK
  7. 7Department of Geriatrics, Aarhus University, Aarhus, Denmark
  8. 8Surgical Intensive Care Unit and Department of Anesthesiology, Cancer Institute, Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, Brazil
  9. 9Department of Haematology, NHS Blood and Transplant/Oxford University Hospitals NHS Trust, Oxford, UK
  1. Correspondence to: A B Docherty annemarie.docherty{at}


Objective To compare patient outcomes of restrictive versus liberal blood transfusion strategies in patients with cardiovascular disease not undergoing cardiac surgery.

Design Systematic review and meta-analysis.

Data sources 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,, WHO International Clinical Trials Registry Platform, ISRCTN Register, and EU Clinical Trials Register. Authors were contacted for data whenever possible.

Trial selection Published and unpublished randomised controlled trials comparing a restrictive with liberal transfusion threshold and that included patients with cardiovascular disease.

Data extraction and synthesis 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.

Main outcome measures 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 (I2=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, I2=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.

Registration PROSPERO CRD42014014251.


  • Contributors: ABD, RO’D, SB, MT, TSW, and SJS conceived and designed the study. Acquisition, analysis, or interpretation of the data: ABD, RO’D, SB, CD, TSW, SJS, LH, MP, and MG acquired, analyses, and interpreted the data. ABD, R’OD, SB, TSW, and SJS drafted the manuscript. ABD and MT carried out the statistical analysis. TSW and SJS supervised the study. ABD had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

  • Funding: None.

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

  • Ethical approval: Not required.

  • Data sharing: No additional data available.

  • Transparency: ABD affirms that this manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 3.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:

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