title: Competing Risk Analysis for Evaluation of Dalteparin Versus Unfractionated Heparin for Venous Thromboembolism in Medical-Surgical Critically Ill Patients.
abstract: Failure to recognize the presence of competing risk or to account for it may result in misleading conclusions. We aimed to perform a competing risk analysis to assess the efficacy of the low molecular weight heparin dalteparin versus unfractionated heparin (UFH) in venous thromboembolism (VTE) in medical-surgical critically ill patients, taking death as a competing risk.This was a secondary analysis of a prospective randomized study of the Prophylaxis for Thromboembolism in Critical Care Trial (PROTECT) database. A total of 3746 medical-surgical critically ill patients from 67 intensive care units (ICUs) in 6 countries receiving either subcutaneous UFH 5000 IU twice daily (n = 1873) or dalteparin 5000 IU once daily plus once-daily placebo (n = 1873) were included for analysis.A total of 205 incident proximal leg deep vein thromboses (PLDVT) were reported during follow-up, among which 96 were in the dalteparin group and 109 were in the UFH group. No significant treatment effect of dalteparin on PLDVT compared with UFH was observed in either the competing risk analysis or standard survival analysis (also known as cause-specific analysis) using multivariable models adjusted for APACHE II score, history of VTE, need for vasopressors, and end-stage renal disease: sub-hazard ratio (SHR) = 0.92, 95% confidence interval (CI): 0.70-1.21, P-value = 0.56 for the competing risk analysis; hazard ratio (HR) = 0.92, 95% CI: 0.68-1.23, P-value = 0.57 for cause-specific analysis. Dalteparin was associated with a significant reduction in risk of pulmonary embolism (PE): SHR = 0.54, 95% CI: 0.31-0.94, P-value = 0.02 for the competing risk analysis; HR = 0.51, 95% CI: 0.30-0.88, P-value = 0.01 for the cause-specific analysis. Two additional sensitivity analyses using the treatment variable as a time-dependent covariate and using as-treated and per-protocol approaches demonstrated similar findings.This competing risk analysis yields no significant treatment effect on PLDVT but a superior effect of dalteparin on PE compared with UFH in medical-surgical critically ill patients. The findings from the competing risk method are in accordance with results from the cause-specific analysis.clinicaltrials.gov Identifier: NCT00182143.
authors.affiliation: From the Department of Clinical Epidemiology and Biostatistics (GL, DC, MAHL, GG, MC, DHA, AH, SDW, LT); Department of Medicine (DC, MAHL, GG, AH); St. Joseph's Healthcare Hamilton, McMaster University, Hamilton, ON (DC, MAHL, MC, AH, LT); Centre de recherche du CHU de Sherbrooke et Université de Sherbrooke, Sherbrooke, QC (FL); Interdepartmental Division of Critical Care Medicine, Departments of Medicine and Physiology, and Institute for Health Policy, Management and Evaluation, University of Toronto (NDF); Department of Medicine, Division of Respirology, University Health Network and Mount Sinai Hospital (NDF); Toronto General Research Institute, Toronto, ON, Canada (NDF); Critical Care and Trauma Division, The George Institute, Sydney, Australia (SF); King Saud bin Abdulaziz University for Health Sciences and King Abdullah International Medical Research Center, Riyadh, Saudi Arabia (YMA); Australian and New Zealand Intensive Care Research Centre (RB, DC); School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia (DC).
authors.forename: Guowei
authors.initials: G
authors.lastname: Li
authors.forename: Deborah J
authors.initials: DJ
authors.lastname: Cook
authors.forename: Mitchell A H
authors.initials: MAH
authors.lastname: Levine
authors.forename: Gordon
authors.initials: G
authors.lastname: Guyatt
authors.forename: Mark
authors.initials: M
authors.lastname: Crowther
authors.forename: Diane
authors.initials: D
authors.lastname: Heels-Ansdell
authors.forename: Anne
authors.initials: A
authors.lastname: Holbrook
authors.forename: Francois
authors.initials: F
authors.lastname: Lamontagne
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Walter
authors.forename: Niall D
authors.initials: ND
authors.lastname: Ferguson
authors.forename: Simon
authors.initials: S
authors.lastname: Finfer
authors.forename: Yaseen M
authors.initials: YM
authors.lastname: Arabi
authors.forename: Rinaldo
authors.initials: R
authors.lastname: Bellomo
authors.forename: D Jamie
authors.initials: DJ
authors.lastname: Cooper
authors.forename: Lehana
authors.initials: L
authors.lastname: Thabane
mesh_terms: D018806:APACHE; D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects; D016638:Critical Illness / Q000401:mortality / Q000628:therapy; D017985:Dalteparin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006493:Heparin / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D007362:Intensive Care Units; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000175:diagnosis / Q000517:prevention & control; D011655:Pulmonary Embolism / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control; D018570:Risk Assessment / Q000379:methods*; D012307:Risk Factors; D013514:Surgical Procedures, Operative / Q000009:adverse effects / Q000401:mortality; D016896:Treatment Outcome; D054556:Venous Thromboembolism / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control
chemical_list: D000925:Anticoagulants; D006493:Heparin; D017985:Dalteparin