PMID- 26356708 OWN - NLM STAT- MEDLINE DCOM- 20151216 LR - 20221005 IS - 1536-5964 (Electronic) IS - 0025-7974 (Print) IS - 0025-7974 (Linking) VI - 94 IP - 36 DP - 2015 Sep TI - Competing Risk Analysis for Evaluation of Dalteparin Versus Unfractionated Heparin for Venous Thromboembolism in Medical-Surgical Critically Ill Patients. PG - e1479 LID - 10.1097/MD.0000000000001479 [doi] LID - e1479 AB - 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. FAU - Li, Guowei AU - Li G AD - 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 Universite 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). FAU - Cook, Deborah J AU - Cook DJ FAU - Levine, Mitchell A H AU - Levine MAH FAU - Guyatt, Gordon AU - Guyatt G FAU - Crowther, Mark AU - Crowther M FAU - Heels-Ansdell, Diane AU - Heels-Ansdell D FAU - Holbrook, Anne AU - Holbrook A FAU - Lamontagne, Francois AU - Lamontagne F FAU - Walter, Stephen D AU - Walter SD FAU - Ferguson, Niall D AU - Ferguson ND FAU - Finfer, Simon AU - Finfer S FAU - Arabi, Yaseen M AU - Arabi YM FAU - Bellomo, Rinaldo AU - Bellomo R FAU - Cooper, D Jamie AU - Cooper DJ FAU - Thabane, Lehana AU - Thabane L CN - PROTECT Investigators for the Canadian Critical Care Trials Group, and the Australian and New Zealand Intensive Care Society Clinical Trials Group LA - eng SI - ClinicalTrials.gov/NCT00182143 GR - MCT78568/Canadian Institutes of Health Research/Canada PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't PL - United States TA - Medicine (Baltimore) JT - Medicine JID - 2985248R RN - 0 (Anticoagulants) RN - 9005-49-6 (Heparin) RN - S79O08V79F (Dalteparin) SB - IM MH - APACHE MH - Aged MH - Anticoagulants/administration & dosage/adverse effects MH - *Critical Illness/mortality/therapy MH - *Dalteparin/administration & dosage/adverse effects MH - Female MH - *Heparin/administration & dosage/adverse effects MH - Humans MH - Intensive Care Units MH - Male MH - Middle Aged MH - Postoperative Complications/diagnosis/prevention & control MH - *Pulmonary Embolism/diagnosis/etiology/prevention & control MH - Risk Assessment/*methods MH - Risk Factors MH - *Surgical Procedures, Operative/adverse effects/mortality MH - Treatment Outcome MH - *Venous Thromboembolism/diagnosis/etiology/prevention & control PMC - PMC4616653 COIS- The authors have no conflicts of interest to disclose. EDAT- 2015/09/12 06:00 MHDA- 2015/12/19 06:00 PMCR- 2015/09/11 CRDT- 2015/09/11 06:00 PHST- 2015/09/11 06:00 [entrez] PHST- 2015/09/12 06:00 [pubmed] PHST- 2015/12/19 06:00 [medline] PHST- 2015/09/11 00:00 [pmc-release] AID - 00005792-201509020-00023 [pii] AID - 10.1097/MD.0000000000001479 [doi] PST - ppublish SO - Medicine (Baltimore). 2015 Sep;94(36):e1479. doi: 10.1097/MD.0000000000001479.