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Randomized Controlled Trial
. 2018 Jun 1;13(6):e0198285.
doi: 10.1371/journal.pone.0198285. eCollection 2018.

Low-molecular-weight heparin venous thromboprophylaxis in critically ill patients with renal dysfunction: A subgroup analysis of the PROTECT trial

Menaka Pai  1   2   3 , Neill K J Adhikari  4   5 , Marlies Ostermann  6 , Diane Heels-Ansdell  7 , James D Douketis  1   7 , Yoanna Skrobik  8 , Ismael Qushmaq  9 , Maureen Meade  1   7 , Gordon Guyatt  1   7 , William Geerts  10 , Michael W Walsh  1   7 , Mark A Crowther  1   2   3 , Jan O Friedrich  5   10 , Lisa Burry  11 , Rinaldo Bellomo  12 , Nilton Brandão da Silva  13 , Rubens Costa Filho  14 , Michael J Cox  15 , Suzana Alves Silva  14 , Deborah J Cook  1   7 ; PROTECT (Prophylaxis for Thromboembolism in Critical Care Trial) Investigators
Affiliations
Randomized Controlled Trial

Low-molecular-weight heparin venous thromboprophylaxis in critically ill patients with renal dysfunction: A subgroup analysis of the PROTECT trial

Menaka Pai et al. PLoS One. .

Abstract

Introduction: There is concern about excessive bleeding when low-molecular-weight heparins (LMWHs) are used for venous thromboembolism (VTE) prophylaxis in renal dysfunction. Our objective was to evaluate whether LMWH VTE prophylaxis was safe and effective in critically ill patients with renal dysfunction by conducting a subgroup analysis of PROTECT, a randomized blinded trial.

Methods: We studied intensive care unit (ICU) patients with pre-ICU dialysis-dependent end-stage renal disease (ESRD; pre-specified subgroup; n = 118), or severe renal dysfunction at ICU admission (defined as ESRD or non-dialysis dependent with creatinine clearance [CrCl] <30 ml/min; post hoc subgroup; n = 590). We compared dalteparin, 5000 IU daily, with unfractionated heparin (UFH), 5000 IU twice daily, and considered outcomes of proximal leg deep vein thrombosis (DVT); pulmonary embolism (PE); any VTE; and major bleeding. Adjusted hazard ratios [HR] were calculated using Cox regression.

Results: In patients with ESRD, there was no significant difference in DVT (8.3% vs. 5.2%, p = 0.76), any VTE (10.0% vs. 6.9%; p = 0.39) or major bleeding (5.0% vs. 8.6%; p = 0.32) between UFH and dalteparin. In patients with severe renal dysfunction, there was no significant difference in any VTE (10.0% vs. 6.4%; p = 0.07) or major bleeding (8.9% vs. 11.0%; p = 0.66) but an increase in DVT with dalteparin (7.6% vs. 3.7%; p = 0.04). Interaction p-values for comparisons of HRs (ESRD versus not) were non-significant.

Conclusions: In critically ill patients with ESRD, or severe renal dysfunction, there was no significant difference in any VTE or major bleeding between UFH and dalteparin. Patients with severe renal dysfunction who received dalteparin had more proximal DVTs than those on UFH; this finding did not hold in patients with ESRD alone.

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Conflict of interest statement

This study received support from Pfizer Canada, which provided dalteparin for Canadian centers, and Eisai, Inc, which provided dalteparin for centers in the United States. Neither group played a role in the design, conduct, analysis, interpretation or write-up of this trial. The authors have no other relevant declarations relating to employment, consultancy, patents, products in development, or marketed products. The competing interests declared here do not alter our adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1
Fig 1. CONSORT diagram: Patient flow through the study.
See this image and copyright information in PMC

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