1. Efficacy of Renally Adjusted Treatment Dose Enoxaparin in Obese Patients with Severe Renal Impairment
Alexas Polk, PharmD
PGY-1 Pharmacy Resident
St. Joseph’s/Candler Health System
Co-Investigators: Hal Richards, PharmD, BCNSP
Madeline Burke, PharmD Candidate

2. Disclosure Statement
Disclosure statement: these individuals have the following to disclose concerning possible personal or financial relationships with commercial entities (or their competitors) that may be referenced in this presentation
Alexas Polk, PharmD: nothing to disclose
Hal Richards, PharmD, BCNSP: nothing to disclose
Madeline Burke, PharmD Candidate: nothing to disclose

3. Background Enoxaparin
Approved for treatment of deep vein thrombosis with or without pulmonary embolism
Dosing strategies:
1 mg/kg Q12h
1.5 mg/kg Q24h
No dose adjustment recommendation for obese patients (BMI ≥ 30 kg/m2)
Dose adjustment for severe renal impairment (CrCl ≤ 30 mL/min)
Reduce to 1 mg/kg Q24h
Enoxaparin sodium injection [package insert]

4. Background Merli et al:
Pharmacodynamic studies with LMWHs
Included obese patients (BMI > 27 kg/m2), up to 196 kg
Once daily enoxaparin use results in 4 fold increase in VTE recurrence
Guidance statement: twice daily enoxaparin dosing is preferred in obese patients and dose capping should be avoided
Excluded those with renal insufficiency defined as Scr >2.03 mg/dL
Once daily= 1.5 mg/kg
Guidance statement released in the Journal of Thrombosis and Thrombolysis in 2016
Merli G et al. Ann Intern Med. 2001;134:
Smythe MA, et al. J Thromb Thrombolysis. 2016;41:

5. Background DeCarolis et al:
Retrospective study to compare major bleeding
Normal renal function (CrCl ≥ 80 mL/min) vs. moderate renal impairment (CrCl mL/min)
4.7 times greater incidence of major bleed in moderate renal impairment
Guidance statement: unfractionated heparin may be preferred in patient with CrCl < 30 mL/min and enoxaparin should be avoided in patients with CrCl < 20 mL/min and those receiving renal replacement therapy
Major bleeding defined as bleeding resulting in death, hospital admission, lengthened hospital stay, or an emergency department visit
105 with normal renal function vs. 59 with moderate renal impairment, received for 6 months
DeCarolis DD, et al. Arch Intern Med. 2012;172(22):
Smythe MA, et al. J Thromb Thrombolysis. 2016;41:

6. Background
Trials evaluating LMWHs did not use Anti-Xa levels to monitor and dose adjust
Levels have been utilized in pregnancy, the extremes of body weight and severe renal impairment
Undefined role and no current correlation between level adjusted dosing and safety or efficacy
Guidance statement: discourage the routine use of Anti-Xa monitoring, except in patients with severe renal failure with suspicion of accumulation
Smythe MA, et al. J Thromb Thrombolysis. 2016;41:

7. Background
No guidance statements are currently available for patients who are both obese and have severe renal impairment
Based on the available literature, we have recommendations for dosing in obese patients and those with severe renal impairment, but not patients with both comorbidities

8. Purpose
To evaluate the effect of renally adjusted treatment dose enoxaparin in obese patients with severe renal impairment on enoxaparin related adverse events and treatment failure

9. Study Objectives Primary Objective Primary Measures
Efficacy of renally adjusted treatment dose enoxaparin in obese patients with severe renal impairment
Primary Measures
Anti-Xa level
New confirmed thromboembolic events
Defined as new DVT/PE, MI or CVA

10. Study Objectives Secondary Objectives Secondary Measures
The effect of renally adjusted treatment dose enoxaparin on adverse events and treatment failure
Secondary Measures
New episodes of clinically significant bleeding
Defined as intracranial hemorrhage, gastrointestinal bleed or any other bleed requiring transfusion

11. Study Center St. Joseph’s/Candler Health System
Community health system with 714 inpatient beds divided between two anchor hospitals
Where enoxaparin is routinely utilized in severely obese patients and those with severe renal impairment including those on various forms of renal replacement therapy

12. Methodology Study design Population
Retrospective, observational investigation
Population
Adult patients, who are obese and have severe renal impairment, admitted to St. Joseph’s/Candler hospital and initiated on renally adjusted treatment-dose enoxaparin from January 1, 2016 to March 3, 2017

13. Methodology Inclusion Criteria Exclusion Criteria
Adults ≥ 18 years of age
Initiation of treatment dose enoxaparin prior to admission
BMI ≥ 30 kg/m2
Enoxaparin discontinuation prior to administration of the third dose
CrCl ≤ 30 mL/min and/or require renal replacement therapy
Receiving any other anticoagulants
Initiated on treatment dose enoxaparin
Calculated using cockcroft-gault equation with adjusted body weight
Dosed utilizing actual body weight rounded to the nearest 10 mg

14. Methodology Treatment groups: CDC Defined Obesity Classes
Class 1- BMI of 30 to < 35
Class 2- BMI of 35 to < 40
Class 3- BMI of > 40
Defining Adult Overweight and Obesity. (2016, June 16).

15. Statistical Analysis One-way ANOVA analysis for continuous variables
Chi-squared analysis for binary variables
Nominal data are reported as counts
P < 0.05 are considered statistically significant

16. Demographics Class I Obesity (N=9) Class II Obesity (N=7)
Class III Obesity
(N=5)
P-value
Age- yr
69.44 ± 9.03
74.86 ± 8.82
69 ± 11.42
0.465
Female sex- no. (%)
3 (33)
5 (71)
2 (40)
0.295
Weight- kg
93.98 ± 8.9
100.3 ± 13.11
± 32.52
0.0002
SCr- mg/dL
4 ± 2.13
3.73 ± 1.59
4.18 ± 0.73
0.905
CrCl- mL/min
20.52 ± 7.12
18.31 ± 6.2
22.43 ± 6.59
0.581
Dialysis- no. (%)
1 (11)
2 (29)
4 (80)
0.031
Dose- mg/24hr
± 22.05
105.7 ± 27
146 ± 28
0.0129
Indication- no. (%)
Afib
4 (57)
3 (60) --
DVT
1 (20) PE
1 (14)
DVT/PE MI
Valve PPX
Class I= kg/m2 Class II= kg/m2 Class III= >40 kg/m2

17. Demographics Class I Obesity (N=9) Class II Obesity (N=7)
Class III Obesity
(N=5)
P-value
Age- yr
69.44 ± 9.03
74.86 ± 8.82
69 ± 11.42
0.465
Female sex- no. (%)
3 (33)
5 (71)
2 (40)
0.295
Weight- kg
93.98 ± 8.9
100.3 ± 13.11
± 32.52
0.0002
SCr- mg/dL
4 ± 2.13
3.73 ± 1.59
4.18 ± 0.73
0.905
CrCl- mL/min
20.52 ± 7.12
18.31 ± 6.2
22.43 ± 6.59
0.581
Dialysis- no. (%)
1 (11)
2 (29)
4 (80)
0.031
Dose- mg/24hr
± 22.05
105.7 ± 27
146 ± 28
0.0129
Indication- no. (%)
Afib
4 (57)
3 (60) --
DVT
1 (20) PE
1 (14)
DVT/PE MI
Valve PPX

18. Demographics Class I Obesity (N=9) Class II Obesity (N=7)
Class III Obesity
(N=5)
P-value
Age- yr
69.44 ± 9.03
74.86 ± 8.82
69 ± 11.42
0.465
Female sex- no. (%)
3 (33)
5 (71)
2 (40)
0.295
Weight- kg
93.98 ± 8.9
100.3 ± 13.11
± 32.52
0.0002
SCr- mg/dL
4 ± 2.13
3.73 ± 1.59
4.18 ± 0.73
0.905
CrCl- mL/min
20.52 ± 7.12
18.31 ± 6.2
22.43 ± 6.59
0.581
Dialysis- no. (%)
1 (11)
2 (29)
4 (80)
0.031
Dose- mg/24hr
± 22.05
105.7 ± 27
146 ± 28
0.0129
Indication- no. (%)
Afib
4 (57)
3 (60) --
DVT
1 (20) PE
1 (14)
DVT/PE MI
Valve PPX
HD=4
CVVHD=2
Peritoneal=1

19. Observed Outcomes Primary Outcome: Anti-Xa Level
Anti-Xa Level- no. (%)
Class I Obesity
(N=9)
Class II Obesity
(N=7)
Class III Obesity
(N=5)
Total
(N=21)
Therapeutic*
5 (56)
3 (43)
2 (40)
10 (47.5)
Sub-therapeutic
1 (11)
1 (20)
2 (9.5)
Supra-therapeutic
2 (28.5)
4 (19)
Unobtainable
2 (22)
5 (24)
Drawn 4 hours after at least the third dose of enoxaparin
RRT- therapeutic= 4, supra= 2, unobtainable= 1
*Therapeutic level= anti-Xa units/mL

20. Observed Outcomes Primary Outcome
Anti-Xa level
No statistically significant difference in class of obesity versus whether or not Anti-Xa level was therapeutic; p = 0.772

21. Observed Outcomes Primary Outcome
New confirmed thromboembolic events
No new DVT, PE, MI or CVA diagnosed after the initiation of enoxaparin

22. Observed Outcomes Secondary Outcome
New episodes of clinically significant bleeding
No new ICH or GI bleeds diagnosed after the initiation of enoxaparin
Class I Obesity
(N=9)
Class II Obesity
(N=7)
Class III Obesity
(N=5)
P-Value
Transfusion Required- no. (%)
5 (56)
2 (29)
4 (80)
Need for transfusion could not easily be correlated to the use of enoxaparin as most transfusions were 2/2 surgery or anemia

23. Discussion
Of the patients initiated on enoxaparin for atrial fibrillation, 9/10 (90%) had a CHADS2 score ≥ 2 and all 10 patients had a HAS-BLED score ≥ 3
Of the patients initiated on enoxaparin for DVT and/or PE, 3/8 (37.5%) were on appropriate VTE prophylaxis prior to discovery

24. Limitations Small, retrospective study limits the external validity
Practice variability in creatinine clearance calculation and enoxaparin dosing weight between institutions
Reliance on nursing to obtain Anti-Xa levels resulted in missed patient inclusion opportunities

25. Conclusions
Renally adjusted treatment dose enoxaparin in obese patients with severe renal impairment appears to be safe and efficacious up to a dose of 180 mg daily in our patients
Further studies are warranted in this population
Evidenced by the lack of any new thromboembolic events or attributable major bleeds

26. Acknowledgements Hal Richards, PharmD, BCNSP
Madeline Burke, PharmD Candidate

27. Self-Assessment Question
Purpose
To evaluate the effect of renally adjusted treatment dose enoxaparin in obese patients with severe renal impairment on enoxaparin related adverse events and treatment failure
Self-Assessment Question
Based on the Merli et al. study once daily enoxaparin dosing in obese patients results in what?

28. Self-Assessment Question
Purpose
To evaluate the effect of renally adjusted treatment dose enoxaparin in obese patients with severe renal impairment on enoxaparin related adverse events and treatment failure
Self-Assessment Question
Based on the Merli et al. study once daily enoxaparin dosing in obese patients results in what?
4-fold increase in VTE recurrence

29. References
Enoxaparin sodium injection [package insert]. Bridgewater, NJ: Sanofi-aventis U.S. LLC; 2013.
Merli G, Spiro TE, Olsson CG, et al. Subcutaneous enoxaparin once or twice daily compared with intravenous unfractionated heparin for treatment of venous thromboembolic disease. Ann Intern Med. 2001;134:
Smythe MA, Prizola J, Dobesh PP, et al. Guidance for the practical management of the heparin anticoagulants in the treatment of venous thromboembolism. J Thromb Thrombolysis. 2016;41:
DeCarolis DD, Thorson JG, Clairmont MA, et al. Enoxaparin outcomes in patients with moderate renal impairment. Arch Intern Med. 2012;172(22):
Defining Adult Overweight and Obesity. (2016, June 16). Retrieved April 14, 2017, from

30. Efficacy of Renally Adjusted Treatment Dose Enoxaparin in Obese Patients with Severe Renal Impairment
Alexas Polk, PharmD
PGY-1 Pharmacy Resident
St. Joseph’s/Candler Health System
Co-Investigators: Hal Richards, PharmD, BCNSP
Madeline Burke, PharmD Candidate