For Patients on Dialysis With Venous Thromboembolism, Low-Molecular-Weight Heparin May Be a Better Option Than Vitamin K Antagonist

Low-molecular-weight heparins (LMWHs) are not traditionally used to treat venous thromboembolism (VTE) in patients on dialysis, but results from a study presented at the 2016 ASH Annual Meeting suggest that the agents do not increase major bleeding risk compared with vitamin K antagonist (VKA) monotherapy – the traditional treatment in this setting.

To compare the risk of major bleeding with LMWH or VKA, Adi J. Klil-Drori, MD, from McGill University in Montreal, Canada, and authors analyzed data from the Q-VTE Study, a population-based cohort of more than 40,000 patients diagnosed with deep-vein thrombosis and pulmonary embolism between 2000 and 2009 in Quebec, Canada.

The analysis included 647 patients on dialysis. Patients were included if they were given VKA or LMWH for the first time within 30 days of their VTE. Patients were followed until they switched or discontinued anticoagulation or until they experienced major bleeding (defined as an emergency room visit or hospital admission for gastrointestinal [GI] bleeding or bleeding into a critical organ).

In the dialysis cohort, 467 patients started VKA, 82 started LMWH, and 96 started both.

More than 90 percent of LMWH monotherapy was dispensed starting in 2004 and later, and 80 percent of LMWH-treated patients had cancer (TABLE). “This may reflect the evidence supporting improved effectiveness of LMWH, compared with VKA for cancer-associated VTE,” Dr. Klil-Drori and authors wrote.

Median daily doses of LMWH were:

  • dalteparin 12,500 IU (n=35)
  • tinzaparin 16,080 IU (n=26)
  • enoxaparin 100 mg (n=19)
  • nadroparin 15,910 IU (n=2)

Patients who received LMWH had a longer median duration of treatment (37 days; range = 22-87 days), compared with those who received VKA (132 days; range = 65-235 days).

There were 22 major bleeding events (86% GI): 20 in VKA-treated patients and two in LMWH-treated patients. No fatal bleeding events occurred. Overall, compared with VKA monotherapy, LMWH monotherapy was not significantly associated with excess major bleeding (adjusted hazard ratio = 1.21; 95% CI 0.20-7.37).

Patients on dialysis with VTE typically do not receive LMWH “because their renal clearance may lead to less predictability in the degree of anticoagulation for a given dose,” the authors explained. However, the results of this study suggest that LMWH monotherapy is as safe as VKA.

“If replicated, these findings indicate LMWH use is feasible in this clinical setting,” the authors concluded.


Reference

Klil-Drori A, Coulombe J, Nessim S, et al. The risk of major bleeding with low-molecular-weight heparins for venous thromboembolism in dialysis patients: the Q-VTE study. Abstract #89. Presented at the 2016 ASH Annual Meeting, December 3, 2016; San Diego, California.

TABLE. Baseline Characteristics of the Cohort, Stratified by Initial Anticoagulation Treatment
Characteristic LMWH and VKA

(n=96)

LMWH

(n=82)

VKA

(n=467)

Age in years (mean, SD) 68.1 (13.2) 68.5 (14) 71.5 (13.9)
   <40 years 4

(4.2%)

4

(4.9%)

22

(4.7%)

   40 to <65 years 20

(20.8%)

23

(28.1%)

72

(15.4%)

   65 to <85 years 67

(69.8%)

49

(59.8%)

315

(67.5%)

   ≥85 years 5

(5.2%)

6

(7.3%)

58

(12.4%)

Male 58

(60.4%)

45

(54.9%)

227

(48.6%)

Inpatient VTE 63

(65.6%)

62

(75.6%)

367

(78.6%)

Hemodialysis 94

(97.9%)

82

(100%)

461

(98.7%)

Years on dialysis (mean, SD) 0.7 (0.9) 0.7 (0.7) 0.8 (0.8)
Pulmonary embolism 39

(40.6%)

28

(34.2%)

182

(39%)

Year of Entry
   2000 2

(2.1%)

1

(1.2%)

39

(8.4%)

   2001 9

(9.4%)

0 57

(12.2%)

   2002 8

(8.3%)

0 40

(8.6%)

   2003 6

(6.3%)

5

(6.1%)

60

(12.9%)

   2004 8

(8.3%)

3

(3.7%)

50

(10.7%)

   2005 7

(7.3%)

7

(8.5%)

44

(9.4%)

   2006 14

(14.6%)

17

(20.7%)

59

(12.6%)

   2007 12

(12.5%)

16 (19.5%) 39

(8.4%)

   2008 16

(16.7%)

14

(17.1%)

40

(8.6%)

   2009 14

(14.6%)

19

(23.2%)

39

(8.4%)

LMWH = low-molecular-weight heparin; VKA = vitamin K antagonist; SD = standard deviation; VTE = venous thromboembolism

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