title: Dalteparin versus unfractionated heparin in critically ill patients.
abstract: BACKGROUND
  The effects of thromboprophylaxis with low-molecular-weight heparin, as compared with unfractionated heparin, on venous thromboembolism, bleeding, and other outcomes are uncertain in critically ill patients.
  
  
  METHODS
  In this multicenter trial, we tested the superiority of dalteparin over unfractionated heparin by randomly assigning 3764 patients to receive either subcutaneous dalteparin (at a dose of 5000 IU once daily) plus placebo once daily (for parallel-group twice-daily injections) or unfractionated heparin (at a dose of 5000 IU twice daily) while they were in the intensive care unit. The primary outcome, proximal leg deep-vein thrombosis, was diagnosed on compression ultrasonography performed within 2 days after admission, twice weekly, and as clinically indicated. Additional testing for venous thromboembolism was performed as clinically indicated. Data were analyzed according to the intention-to-treat principle.
  
  
  RESULTS
  There was no significant between-group difference in the rate of proximal leg deep-vein thrombosis, which occurred in 96 of 1873 patients (5.1%) receiving dalteparin versus 109 of 1873 patients (5.8%) receiving unfractionated heparin (hazard ratio in the dalteparin group, 0.92; 95% confidence interval [CI], 0.68 to 1.23; P=0.57). The proportion of patients with pulmonary emboli was significantly lower with dalteparin (24 patients, 1.3%) than with unfractionated heparin (43 patients, 2.3%) (hazard ratio, 0.51; 95% CI, 0.30 to 0.88; P=0.01). There was no significant between-group difference in the rates of major bleeding (hazard ratio, 1.00; 95% CI, 0.75 to 1.34; P=0.98) or death in the hospital (hazard ratio, 0.92; 95% CI, 0.80 to 1.05; P=0.21). In prespecified per-protocol analyses, the results were similar to those of the main analyses, but fewer patients receiving dalteparin had heparin-induced thrombocytopenia (hazard ratio, 0.27; 95% CI, 0.08 to 0.98; P=0.046).
  
  
  CONCLUSIONS
  Among critically ill patients, dalteparin was not superior to unfractionated heparin in decreasing the incidence of proximal deep-vein thrombosis. (Funded by the Canadian Institutes of Health Research and others; PROTECT ClinicalTrials.gov number, NCT00182143.).
authors.forename: Deborah
authors.initials: D
authors.lastname: Cook
authors.forename: Maureen
authors.initials: M
authors.lastname: Meade
authors.forename: Gordon
authors.initials: G
authors.lastname: Guyatt
authors.forename: Stephen
authors.initials: S
authors.lastname: Walter
authors.forename: Diane
authors.initials: D
authors.lastname: Heels-Ansdell
authors.forename: Theodore E
authors.initials: TE
authors.lastname: Warkentin
authors.forename: Nicole
authors.initials: N
authors.lastname: Zytaruk
authors.forename: Mark
authors.initials: M
authors.lastname: Crowther
authors.forename: William
authors.initials: W
authors.lastname: Geerts
authors.forename: D Jamie
authors.initials: DJ
authors.lastname: Cooper
authors.forename: Shirley
authors.initials: S
authors.lastname: Vallance
authors.forename: Ismael
authors.initials: I
authors.lastname: Qushmaq
authors.forename: Marcelo
authors.initials: M
authors.lastname: Rocha
authors.forename: Otavio
authors.initials: O
authors.lastname: Berwanger
authors.forename: Nicholas E
authors.initials: NE
authors.lastname: Vlahakis
mesh_terms: D000925:Anticoagulants / Q000009:adverse effects / Q000627:therapeutic use*; D016638:Critical Illness / Q000401:mortality / Q000628:therapy*; D017985:Dalteparin / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced; D006493:Heparin / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D015994:Incidence; D007279:Injections, Subcutaneous; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011655:Pulmonary Embolism / Q000453:epidemiology / Q000517:prevention & control; D013921:Thrombocytopenia / Q000139:chemically induced; D013923:Thromboembolism / Q000517:prevention & control; D020246:Venous Thrombosis / Q000453:epidemiology / Q000517:prevention & control*
chemical_list: D000925:Anticoagulants; D006493:Heparin; D017985:Dalteparin