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 Rousseau; Julie 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

doi:10.1097/MD.0000000000001479

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

Faculty of Medicine, Health and Human Sciences

Research output: Contribution to journal › Article › peer-review

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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 language	English
Article number	e1479
Pages (from-to)	1-8
Number of pages	8
Journal	Medicine (United States)
Volume	94
Issue number	36
DOIs	https://doi.org/10.1097/MD.0000000000001479
Publication status	Published - 1 Sept 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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10.1097/MD.0000000000001479Licence: CC BY-NC

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Li, G., Cook, D. J., Levine, M. A. H., Guyatt, G., Crowther, M., Heels-Ansdell, D., Holbrook, A., Lamontagne, F., Walter, S. D., Ferguson, N. D., Finfer, S., Arabi, Y. M., Bellomo, R., Cooper, D. J., Thabane, L., Lesur, O., Proulx, S., Cloutier, S., Bolduc, B., ... Harer, N. (2015). Competing risk analysis for evaluation of dalteparin versus unfractionated heparin for venous thromboembolism in medical-surgical critically ill patients. Medicine (United States), 94(36), 1-8. [e1479]. https://doi.org/10.1097/MD.0000000000001479

@article{4ec7fb75cc59414c9def164284882d62,

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 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.",

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

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.",

year = "2015",

month = sep,

day = "1",

doi = "10.1097/MD.0000000000001479",

language = "English",

volume = "94",

pages = "1--8",

journal = "Medicine (United States)",

issn = "0025-7974",

publisher = "Lippincott Williams and Wilkins",

number = "36",

}

Li, G, Cook, DJ, Levine, MAH, Guyatt, G, Crowther, M, Heels-Ansdell, D, Holbrook, A, Lamontagne, F, Walter, SD, Ferguson, ND, Finfer, S, Arabi, YM, Bellomo, R, Cooper, DJ, Thabane, L, Lesur, O, Proulx, S, Cloutier, S, Bolduc, B, Rousseau, MP, Leblond, J, Schmutz, G, McIntyre, L, Hebert, P, Watpool, I, McArdle, T, Gaudert, C, Marchand, P, Davidson, C, Dugal, AM, Fetzer, S, Shabana, W, Castonguay, M, Anwar, S, Kozarenko, V, Mohammad, S, Sikalska, S, Gauthier, S, Mustafa, A, Dodek, P, Ashley, BJ, Mans, S, Pavan, M, Leipsic, J, Meiersdorf, S, Yoong, A, Flores, FA, Mumtaz, H, Ng, P, Fix, C, Meade, M, Hand, L, Biljan, M, Patlas, M, Broughton, L, Degrow, L, Connor, D, Tuhy, M, Whyte, D, Jefferson, M, Aarts, K, Vooys, L, Anzovino, M, Skrobik, Y, Harvey, J, Chitu, S, Quach, M, Pinet, L, Muscedere, J, Fleury, S, Godfrey, N, Hammond, S, Mann, E, Myers, M, Robinson, A, Grey, C, Saurbrei, E, Cox, J, Nugent, A, Kolesar, J, Fisher, A, Northrup-St-Onge, A, Paterson-Skeete, M, Schlottke, W, Bertrim, W, Marshall, C, Cook, D, McDonald, E, Tkaczyk, A, Clarke, F, Wallace, C, Schiff, D, McDonald, J, Todd, S, Harkness, P, Medic, A, Andrews, J, Sands, M, Hall, I, Boniakowski, T, Lichty, K, Seppelt, I, Weisbrodt, L, Bond, R, Suen, S, Trinh, J, Hall, R, Huang, R, Chow, H, Reece, G, Sara, T, Nand, K, Ibrahim, R, Jarrett, J, Seehra, J, Stringer, G, Alhashemi, J, Shalabi, S, Ainosah, R, Sonbul, JA, Gloriani, R, Huertazuela, R, Abbas, I, Chavez, J, Toum, NE, Alsultan, M, Arabi, Y, Brits, R, Da Rocha, MG, Kramer, A, Hadrich, M, Berwanger, O, Romano, E, Buehler, AM, Ostermann, M, Treacher, D, Sherry, T, Smith, J, Sanderson, B, Ng, J, Brooks, J, Lim, L, Lei, K, Tunstell, P, McKenzie, C, Cicirello, F, Padayachee, TS, Thomas, N, Arnold, AJ, Vlahakis, NE, Meade, L, Bauer, D, Lewis, B & Harer, N 2015, 'Competing risk analysis for evaluation of dalteparin versus unfractionated heparin for venous thromboembolism in medical-surgical critically ill patients', Medicine (United States), vol. 94, no. 36, e1479, pp. 1-8. https://doi.org/10.1097/MD.0000000000001479

TY - JOUR

T1 - Competing risk analysis for evaluation of dalteparin versus unfractionated heparin for venous thromboembolism in medical-surgical critically ill patients

AU - Li, Guowei

AU - Cook, Deborah J.

AU - Levine, Mitchell A H

AU - Guyatt, Gordon

AU - Crowther, Mark

AU - Heels-Ansdell, Diane

AU - Holbrook, Anne

AU - Lamontagne, Francois

AU - Walter, Stephen D.

AU - Ferguson, Niall D.

AU - Finfer, Simon

AU - Arabi, Yaseen M.

AU - Bellomo, Rinaldo

AU - Cooper, D. Jamie

AU - Thabane, Lehana

AU - Lesur, Olivier

AU - Proulx, Sandra

AU - Cloutier, Sylvie

AU - Bolduc, Brigitte

AU - Rousseau, Marie Pierre

AU - Leblond, Julie

AU - Schmutz, Gerard

AU - McIntyre, Lauralyn

AU - Hebert, Paul

AU - Watpool, Irene

AU - McArdle, Tracy

AU - Gaudert, Claude

AU - Marchand, Paule

AU - Davidson, Carson

AU - Dugal, Anne Marie

AU - Fetzer, Susan

AU - Shabana, Wael

AU - Castonguay, Marc

AU - Anwar, Sohail

AU - Kozarenko, Valentina

AU - Mohammad, Shahina

AU - Sikalska, Svitlana

AU - Gauthier, Suzanne

AU - Mustafa, Arif

AU - Dodek, Peter

AU - Ashley, Betty Jean

AU - Mans, Sheilagh

AU - Pavan, Mara

AU - Leipsic, Jonathon

AU - Meiersdorf, Sam

AU - Yoong, Adrian

AU - Flores, Francisco Avila

AU - Mumtaz, Hina

AU - Ng, Patrick

AU - Fix, Cathy

AU - Meade, Maureen

AU - Hand, Lori

AU - Biljan, Maya

AU - Patlas, Michael

AU - Broughton, Lianne

AU - Degrow, Lucy

AU - Connor, Dianna

AU - Tuhy, Maggie

AU - Whyte, Dawn

AU - Jefferson, Meaghan

AU - Aarts, Kaitlyn

AU - Vooys, Lindsay

AU - Anzovino, Michael

AU - Skrobik, Yoanna

AU - Harvey, Johanne

AU - Chitu, Stefania

AU - Quach, Marceline

AU - Pinet, Linda

AU - Muscedere, John

AU - Fleury, Susan

AU - Godfrey, Nicole

AU - Hammond, Sharlene

AU - Mann, Elizabeth

AU - Myers, Monica

AU - Robinson, Amber

AU - Grey, Chris

AU - Saurbrei, Eric

AU - Cox, Jennifer

AU - Nugent, Angela

AU - Kolesar, Julie

AU - Fisher, Amy

AU - Northrup-St-Onge, Amy

AU - Paterson-Skeete, Marshaw

AU - Schlottke, Wendy

AU - Bertrim, Wendy

AU - Marshall, Cathy

AU - Cook, Debrah

AU - McDonald, Ellen

AU - Tkaczyk, Andrea

AU - Clarke, France

AU - Wallace, Christine

AU - Schiff, David

AU - McDonald, Jennifer

AU - Todd, Sarah

AU - Harkness, Patty

AU - Medic, Angela

AU - Andrews, Joanna

AU - Sands, Moira

AU - Hall, Iwona

AU - Boniakowski, Tanya

AU - Lichty, Kim

AU - Seppelt, Ian

AU - Weisbrodt, Leonie

AU - Bond, Robyn

AU - Suen, Stella

AU - Trinh, Jason

AU - Hall, Roger

AU - Huang, Richard

AU - Chow, Helen

AU - Reece, Graham

AU - Sara, Treena

AU - Nand, Kiran

AU - Ibrahim, Rabsima

AU - Jarrett, James

AU - Seehra, Jagdish

AU - Stringer, Gill

AU - Alhashemi, Jamal

AU - Shalabi, Sanaa

AU - Ainosah, Randa

AU - Sonbul, Julie Ann

AU - Gloriani, Rustico

AU - Huertazuela, Rosalinda

AU - Abbas, Ibrahim

AU - Chavez, Judy

AU - Toum, Nahid El

AU - Alsultan, Mohammed

AU - Arabi, Yasen

AU - Brits, Riette

AU - Da Rocha, Marcelo Garcia

AU - Kramer, Andrea

AU - Hadrich, Martha

AU - Berwanger, Otavio

AU - Romano, Edson

AU - Buehler, Anna Maria

AU - Ostermann, Marlies

AU - Treacher, David

AU - Sherry, Tony

AU - Smith, John

AU - Sanderson, Barnaby

AU - Ng, Josephine

AU - Brooks, John

AU - Lim, Ling

AU - Lei, Katie

AU - Tunstell, Paul

AU - McKenzie, Cathy

AU - Cicirello, Francesco

AU - Padayachee, T. S.

AU - Thomas, Nicholas

AU - Arnold, Andrew J.

AU - Vlahakis, Nicholas E.

AU - Meade, Laurie

AU - Bauer, Debbie

AU - Lewis, Bradley

AU - Harer, Nora

N1 - 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.

PY - 2015/9/1

Y1 - 2015/9/1

N2 - 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.

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 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.

UR - http://www.scopus.com/inward/record.url?scp=84941644538&partnerID=8YFLogxK

U2 - 10.1097/MD.0000000000001479

DO - 10.1097/MD.0000000000001479

M3 - Article

C2 - 26356708

AN - SCOPUS:84941644538

SN - 0025-7974

VL - 94

SP - 1

EP - 8

JO - Medicine (United States)

JF - Medicine (United States)

IS - 36

M1 - e1479

ER -

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

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