Competing risk analysis for evaluation of dalteparin versus unfractionated heparin for venous thromboembolism in medical-surgical critically ill patients

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*, Olivier Lesur, Sandra Proulx, Sylvie Cloutier, Brigitte Bolduc, Marie Pierre RousseauJulie Leblond, Gerard Schmutz, Lauralyn McIntyre, Paul Hebert, Irene Watpool, Tracy McArdle, Claude Gaudert, Paule Marchand, Carson Davidson, Anne Marie Dugal, Susan Fetzer, Wael Shabana, Marc Castonguay, Sohail Anwar, Valentina Kozarenko, Shahina Mohammad, Svitlana Sikalska, Suzanne Gauthier, Arif Mustafa, Peter Dodek, Betty Jean Ashley, Sheilagh Mans, Mara Pavan, Jonathon Leipsic, Sam Meiersdorf, Adrian Yoong, Francisco Avila Flores, Hina Mumtaz, Patrick Ng, Cathy Fix, Maureen Meade, Lori Hand, Maya Biljan, Michael Patlas, Lianne Broughton, Lucy Degrow, Dianna Connor, Maggie Tuhy, Dawn Whyte, Meaghan Jefferson, Kaitlyn Aarts, Lindsay Vooys, Michael Anzovino, Yoanna Skrobik, Johanne Harvey, Stefania Chitu, Marceline Quach, Linda Pinet, John Muscedere, Susan Fleury, Nicole Godfrey, Sharlene Hammond, Elizabeth Mann, Monica Myers, Amber Robinson, Chris Grey, Eric Saurbrei, Jennifer Cox, Angela Nugent, Julie Kolesar, Amy Fisher, Amy Northrup-St-Onge, Marshaw Paterson-Skeete, Wendy Schlottke, Wendy Bertrim, Cathy Marshall, Debrah Cook, Ellen McDonald, Andrea Tkaczyk, France Clarke, Christine Wallace, David Schiff, Jennifer McDonald, Sarah Todd, Patty Harkness, Angela Medic, Joanna Andrews, Moira Sands, Iwona Hall, Tanya Boniakowski, Kim Lichty, Ian Seppelt, Leonie Weisbrodt, Robyn Bond, Stella Suen, Jason Trinh, Roger Hall, Richard Huang, Helen Chow, Graham Reece, Treena Sara, Kiran Nand, Rabsima Ibrahim, James Jarrett, Jagdish Seehra, Gill Stringer, Jamal Alhashemi, Sanaa Shalabi, Randa Ainosah, Julie Ann Sonbul, Rustico Gloriani, Rosalinda Huertazuela, Ibrahim Abbas, Judy Chavez, Nahid El Toum, Mohammed Alsultan, Yasen Arabi, Riette Brits, Marcelo Garcia Da Rocha, Andrea Kramer, Martha Hadrich, Otavio Berwanger, Edson Romano, Anna Maria Buehler, Marlies Ostermann, David Treacher, Tony Sherry, John Smith, Barnaby Sanderson, Josephine Ng, John Brooks, Ling Lim, Katie Lei, Paul Tunstell, Cathy McKenzie, Francesco Cicirello, T. S. Padayachee, Nicholas Thomas, Andrew J. Arnold, Nicholas E. Vlahakis, Laurie Meade, Debbie Bauer, Bradley Lewis, Nora Harer

*Corresponding author for this work

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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 endstage 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 causespecific 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 timedependent 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 riskmethod are in accordancewith results fromthe cause-specific analysis.

Original languageEnglish
Article numbere1479
Pages (from-to)1-8
Number of pages8
JournalMedicine (United States)
Volume94
Issue number36
DOIs
Publication statusPublished - 1 Sep 2015

Bibliographical note

Copyright the Author(s) 2015. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

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