This study compared the efficacy and safety of tranexamic acid (TXA) and epsilon-aminocaproic acid (EACA) in 112 patients undergoing major cardiac or orthopedic surgery who received at least one dose of an antifibrinolytic. There were no clinically significant differences found between the drugs in terms of efficacy endpoints like change in hemoglobin levels and estimated blood loss or safety endpoints like renal dysfunction and thromboembolic events. While estimated blood loss was significantly higher in cardiac patients receiving TXA, the overall costs per patient were significantly greater for TXA. The study reinforces the hospital's current policy of preferring EACA over TXA due to no advantages of switching and its consistency with previous literature

1. Pharmacologic blood conservation: Comparative
efficacy and safety of tranexamic acid and ε-
aminocaproic acid in major surgery
Jimmy Gonzalez, Pharm.D. Englewood Hospital and Medical Center
PGY-1 Pharmacy Practice Resident 350 Engle Street
Englewood, NJ 07631

2. Objectives
• Describe the role of antifibrinolytics in major surgery
• Evaluate the safety and efficacy profiles of ε-
aminocaproic acid (EACA) and tranexamic acid (TXA)
2

3. Background
• Multiple pharmacologic agents used in reducing
perioperative blood loss
− Aprotinin
− EACA & TXA
• Similar outcomes with both EACA & TXA:
− Perioperative bleeding
− Renal dysfunction
− Thromboembolic events
− Seizure
− 30-day all-cause mortality
3
N Engl J Med 2008;358(22):2319-31
Ann Pharmacother 2014;48(12):1563-9

4. Study Rationale
• EACA and TXA are both lysine analogues
− Antifibrinolytics used off-label for CTS
• EHMC preferentially uses EACA in surgery
− Orthopedic surgeons interested in TXA switch
• Recent drug shortages necessitated use of TXA
4ASHP Drug Shortages Bulletin

5. Study Objective
• Determine if any differences exist between EACA and
TXA therapies in major surgery with regard to
hemostatic parameters and side effect profiles
5

6. Methods
• Study Design
− Retrospective chart review
− Data from January 1, 2013 to September 24, 2014
− Identified by medication administration records (MARs)
• Statistical Tests
− Continuous data
• T test, Mann Whitney U test
− Nominal data
• Fisher’s exact test
− α=0.05 (two-tailed)
6

7. Subject Selection Criteria
Inclusion Criteria
• Patient age 18-100 years
• Underwent major cardiac or
orthopedic surgery
• Received ≥1 dose of EACA or
TXA
Exclusion Criteria
• Age <18 or >100 years
• Thrombocytopenia
(plts<100,000 cells/mm3)
• Coagulopathy (INR>1.5)
• tPA use immediately prior to
operation
• Active intravascular clotting
(e.g. DIC)
• Pre-existing thromboembolic
disease
• Pregnancy
7

8. Study Endpoints
Primary Efficacy Endpoints
• Change in pre- and post-Hgb
• Units of allogeneic blood
transfused
• Estimated blood loss (EBL)
• 30-day all-cause mortality
Primary Safety Endpoints
• Renal dysfunction†
• Thromboembolic events
• Seizure
• Anaphylaxis
8
†Renal dysfunction defined as: (1) Doubling SCr baseline or (2) SCr > 1.7 mg/dL
N Engl J Med. 2008;358(22):2319-31
Ann Pharmacother. 2014;48(12):1563-9

9. Results: Baseline Demographics
9
N = 112
EACA
n = 65
(58%)
Cardiac
n = 45
(69.2%)
Orthopedic
n = 20
(30.8%)
TXA
n = 47
(42%)
Cardiac
n = 39
(83.0%)
Orthopedic
n = 8
(17.0%)

10. Results: Baseline Demographics
EACA
(n=65)
TXA
(n=47)
Age (yr) (median) 63 65
Weight (kg) 83.9 89.1
Height (cm) 169.4 170.9
Male 37 (56.9%) 32 (68.1%)
Bloodless 10 (15.4%) 5 (10.6%)
Pre-Hgb (g/dL) 13.2 13.3
10

11. Surgery Subtypes
11Cardiac Orthopedic
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
CABG CABG +
AVR
CABG +
MVR
AAA MVR AVR AVR +
MVR
THR TKR
PercentageofTotalSurgeries
EACA TXA

12. Results: Baseline Subgroups
12
EACA TXA
Cardiac
(n=40)
Orthopedic
(n=15)
Bloodless
(n=10)
Cardiac
(n=36)
Orthopedic
(n=6)
Bloodless
(n=5)
Age (yr) 63 (39-89) 67 (43-83) 63.5 (20-81) 67 (43-91) 65 (55-76) 54 (48-73)
Weight (kg) 82.9 ± 14.9 83.8 ± 18.6 87.9 ± 19.7 83.5 ± 19.0 94.2 ± 12.8 123.1 ±
26.4
Height (cm) 171.7 ± 11.9 164.3 ± 9.5 167.9 ± 10.0 169.6 ± 12.2 176.3 ± 4.4 173.2 ±
4.2
Male 31 (78%) 4 (27%) 2 (20%) 22 (61%) 5 (83%) 5 (100%)
Pre-Hgb (g/dL) 13.0 ± 1.8 13.7 ± 0.6 13.6 ± 1.3 12.9 ± 1.7 14.3 ± 0.6 14.6 ± 0.7

13. Results: Efficacy Endpoints
EACA
(n=65)
TXA
(n=49)
P value
Pre-Hgb (g/dL) 13.4 ± 1.5 13.3 ± 1.6 0.9226*
Δ Hgb (g/dL) 2.47 ± 1.3 2.95 ± 1.3 0.1258†
pRBCs transfused (units) Mean: 0.323 ± 0.85
Median: 0
Mean: 0.638 ± 1.39
Median: 0
0.3420*
Transfusion needed (n) 9 (13.8%) 9 (18.4%) 0.6030‡
EBL (mL) 367 ± 276 413 ± 274 0.1259†
13
* Calculated by T test
† Calculated by Mann Whitney U test
‡ Calculated by Fisher’s exact test

14. Results: Distribution of EBL
14
0
1
2
3
4
5
6
7
8
9
Frequency
Estimated Blood Loss (mL)
EACA
TXA

15. Results: Subgroup Analysis
15
* Calculated by T test
† Calculated by Mann Whitney U test
‡ Calculated by Fisher’s exact test
EACA TXA P value
Cardiac Surgery (n=40) (n=36)
Δ Hgb (g/dL) 2.56 ± 1.4 2.99 ± 1.3 0.2954†
EBL (mL) 385 ± 247 508 ± 245 0.0326*
Transfusion needed 8 (20%) 9 (25%) 0.7835‡
Orthopedic Surgery (n=15) (n=6)
Δ Hgb (g/dL)* 2.22 ± 1.0 2.57 ± 0.9 0.4579*
EBL (mL)* 333 ± 349 250 ± 217 >0.9999†
Transfusion needed 1 (7%) 0 1.0000‡
Bloodless (n=10) (n=5)
Δ Hgb (g/dL) 2.47 ± 1.3 3.14 ± 2.1 0.5404*
EBL (mL) 347 ± 288 230 ± 268 0.4605*
Transfusion needed 0 0 N/A

16. Results: Safety Endpoints
16* Died of cardiac arrest 5 hr s/p surgery
EACA TXA P value
Renal dysfunction
General 8 (12.3%) 5 (10.6%) 1.0000
Cardiac 7 (17.5%) 3 (8.3%) 0.3168
Orthopedic 0 1 (16.7%) 0.2857
Bloodless 1 (10%) 1 (20%) 1.0000
Seizure 0 0 -
Anaphylaxis 0 0 -
Venous thromboembolism 0 0 -
30-day all-cause mortality 0 1 (2.1%)* -

17. Estimated Costs per Patient
17
$-
$5.00
$10.00
$15.00
$20.00
$25.00
$30.00
$35.00
$40.00
$45.00
$50.00
Overall Cardiac Orthopedic Bloodless
$12.66 $13.71 $10.40 $11.82
$37.46 $36.84 $32.61
$47.83
AverageCost($)
EACA Costs TXA Costs

18. Discussion
• No clinically significant difference between EACA and
TXA in examined efficacy and safety outcomes
− Statistically significant difference in EBL of cardiac patients
− Significantly higher cost per patient
− Validates drug shortage option
• Reinforcement of current EHMC hospital policy
− EACA preferred over TXA
− No advantage in switching over to TXA
• Consistent with previously published literature
18

19. Limitations
• Statistical power
− Small subgroup size
• Inaccuracies in EBL documentation
− Skewed distribution of data
• Lack of pre-operative comorbidity scores and CPB time
19

20. Acknowledgements
• Jacqueline Takere, Pharm.D., CCRP
• Joseph Cruz, Pharm.D., BCPS
• Jeffery Nemeth, BSPh, Pharm.D, MPA
• James Regan, RPh, MIS, MS
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21. Questions
• The floor is open to questions and comments
21