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: Guowei Li, Deborah J Cook, Mitchell A H Levine, Gordon Guyatt, Mark Crowther, Diane Heels-Ansdell, Anne Holbrook, Francois Lamontagne, Stephen D Walter, Niall D Ferguson, Simon Finfer, Yaseen M Arabi, Rinaldo Bellomo, D Jamie Cooper, Lehana Thabane, PROTECT Investigators for the Canadian Critical Care Trials Group, and the Australian and New Zealand Intensive Care Society Clinical Trials Group
• Journal: Medicine (Medicine (Baltimore)) Vol. 94 Issue 36 Pg. e1479 (Sep 2015) ISSN: 1536-5964 [Electronic] United States
• PMID: 26356708 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Anticoagulants
• Heparin
• Dalteparin

Topics

• APACHE
• Aged
• Anticoagulants (administration & dosage, adverse effects)
• Critical Illness (mortality, therapy)
• Dalteparin (administration & dosage, adverse effects)
• Female
• Heparin (administration & dosage, adverse effects)
• Humans
• Intensive Care Units
• Male
• Middle Aged
• Postoperative Complications (diagnosis, prevention & control)
• Pulmonary Embolism (diagnosis, etiology, prevention & control)
• Risk Assessment (methods)
• Risk Factors
• Surgical Procedures, Operative (adverse effects, mortality)
• Treatment Outcome
• Venous Thromboembolism (diagnosis, etiology, prevention & control)