title: Liberal versus restrictive blood transfusion strategy: 3-year survival and cause of death results from the FOCUS randomised controlled trial.
abstract: BACKGROUND
  Blood transfusion might affect long-term mortality by changing immune function and thus potentially increasing the risk of subsequent infections and cancer recurrence. Compared with a restrictive transfusion strategy, a more liberal strategy could reduce cardiac complications by lowering myocardial damage, thereby reducing future deaths from cardiovascular disease. We aimed to establish the effect of a liberal transfusion strategy on long-term survival compared with a restrictive transfusion strategy.
  
  
  METHODS
  In the randomised controlled FOCUS trial, adult patients aged 50 years and older, with a history of or risk factors for cardiovascular disease, and with postoperative haemoglobin concentrations lower than 100 g/L within 3 days of surgery to repair a hip fracture, were eligible for enrolment. Patients were recruited from 47 participating hospitals in the USA and Canada, and eligible participants were randomly allocated in a 1:1 ratio by a central telephone system to either liberal transfusion in which they received blood transfusion to maintain haemoglobin level at 100 g/L or higher, or restrictive transfusion in which they received blood transfusion when haemoglobin level was lower than 80 g/L or if they had symptoms of anaemia. In this study, we analysed the long-term mortality of patients assigned to the two transfusion strategies, which was a secondary outcome of the FOCUS trial. Long-term mortality was established by linking the study participants to national death registries in the USA and Canada. Treatment assignment was not masked, but investigators who ascertained mortality and cause of death were masked to group assignment. Analyses were by intention to treat. The FOCUS trial is registered with ClinicalTrials.gov, number NCT00071032.
  
  
  RESULTS
  Between July 19, 2004, and Feb 28, 2009, 2016 patients were enrolled and randomly assigned to the two treatment groups: 1007 to the liberal transfusion strategy and 1009 to the restrictive transfusion strategy. The median duration of follow-up was 3·1 years (IQR 2·4-4·1 years), during which 841 (42%) patients died. Long-term mortality did not differ significantly between the liberal transfusion strategy (432 deaths) and the restrictive transfusion strategy (409 deaths) (hazard ratio 1·09 [95% CI 0·95-1·25]; p=0·21).
  
  
  CONCLUSIONS
  Liberal blood transfusion did not affect mortality compared with a restrictive transfusion strategy in a high-risk group of elderly patients with underlying cardiovascular disease or risk factors. The underlying causes of death did not differ between the trial groups. These findings do not support hypotheses that blood transfusion leads to long-term immunosuppression that is severe enough to affect long-term mortality rate by more than 20-25% or cause of death.
  
  
  BACKGROUND
  National Heart, Lung, and Blood Institute.
authors.affiliation: Division of General Internal Medicine, Department of Medicine, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, USA. Electronic address: jeffrey.carson@rutgers.edu.
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Carson
authors.affiliation: Department of Anesthesiology and Critical Care, Johns Hopkins Bayview Medical Center, Baltimore, MD, USA.
authors.forename: Frederick
authors.initials: F
authors.lastname: Sieber
authors.affiliation: Division of General Internal Medicine, University of Calgary, Calgary, AB, Canada.
authors.forename: Donald Richard
authors.initials: DR
authors.lastname: Cook
authors.affiliation: Department of Statistics, Rutgers University, New Brunswick, NJ, USA.
authors.forename: Donald R
authors.initials: DR
authors.lastname: Hoover
authors.affiliation: Division of General Internal Medicine, Department of Medicine, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, USA.
authors.forename: Helaine
authors.initials: H
authors.lastname: Noveck
authors.affiliation: Department of Medicine, Saint Louis University, Saint Louis, MO, USA.
authors.forename: Bernard R
authors.initials: BR
authors.lastname: Chaitman
authors.affiliation: Department of Anesthesiology and Critical Care, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Lee
authors.initials: L
authors.lastname: Fleisher
authors.affiliation: Departments of Physical Therapy and Surgery, Division of Orthopaedic Surgery, University of Alberta, Edmonton, AB, Canada.
authors.forename: Lauren
authors.initials: L
authors.lastname: Beaupre
authors.affiliation: Department of Orthopedic Surgery, New York-Presbyterian Hospital at Columbia University, New York, NY, USA.
authors.forename: William
authors.initials: W
authors.lastname: Macaulay
authors.affiliation: Rutgers School of Public Health, Piscataway, NJ, USA.
authors.forename: George G
authors.initials: GG
authors.lastname: Rhoads
authors.affiliation: Division of Geriatrics, Maimonides Medical Center, Brooklyn, New York, NY, USA.
authors.forename: Barbara
authors.initials: B
authors.lastname: Paris
authors.affiliation: Division of Geriatrics, Maimonides Medical Center, Brooklyn, New York, NY, USA.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Zagorin
authors.affiliation: Department of Orthopaedic Surgery, University of Western Ontario, London, ON, Canada.
authors.forename: David W
authors.initials: DW
authors.lastname: Sanders
authors.affiliation: Department of Anesthesia, Surgeons Surgery Center, Cumberland, MD, USA.
authors.forename: Khwaja J
authors.initials: KJ
authors.lastname: Zakriya
authors.affiliation: Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: Jay
authors.initials: J
authors.lastname: Magaziner
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000097:blood / Q000453:epidemiology / Q000628:therapy; D001803:Blood Transfusion / Q000706:statistics & numerical data*; D002170:Canada / Q000453:epidemiology; D002318:Cardiovascular Diseases / Q000401:mortality / Q000517:prevention & control; D002423:Cause of Death; D005260:Female; D006454:Hemoglobins / Q000032:analysis; D006620:Hip Fractures / Q000601:surgery*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011182:Postoperative Care / Q000009:adverse effects / Q000379:methods*; D012307:Risk Factors; D016037:Single-Blind Method; D016019:Survival Analysis; D065227:Transfusion Reaction; D014481:United States / Q000453:epidemiology
chemical_list: D006454:Hemoglobins