1. Transfusion is Associated with Increased 30-Day Mortality and Ischemic Complications in Non-ST Elevation Acute Coronary Syndromes: The ACUITY Trial Steven V. Manoukian1, Michele D. Voeltz1, Frederick Feit2, Roxana Mehran3, George D. Dangas3, Eugenia Nikolsky3, A. Michael Lincoff4, Spencer B. King5, III, E. Magnus Ohman6, Gregg W. Stone3 1Emory University School of Medicine, Atlanta, GA 2New York University School of Medicine, New York, NY 3Columbia University Medical Center, New York, NY 4The Cleveland Clinic, Cleveland, OH 5Fuqua Heart Center, Atlanta, GA 6Duke University Medical Center, Durham, NC

2. Relevant Conflict of Interest Statement
Within the past 12 months, I or my spouse/partner have had a financial interest/arrangement or affiliation with the organization(s) listed below.
Steven V. Manoukian, MD, FACC The Medicines Co.
Research Support
Consultant
Speaker
sanofi aventis/BMS

3. Background: Transfusion in ACS and PCI
Blood product transfusion is an important complication in acute coronary syndromes (ACS) and percutaneous coronary intervention (PCI) patients treated with potent antithrombotic and antiplatelet agents.
Recent data suggest that transfusion is associated with an increase in adverse outcomes in ACS and PCI, including mortality.
We assessed the impact of transfusion on mortality and ischemic events in patients with ACS from the ACUITY Trial.
Manoukian SV, Voeltz MD, Feit F et al. TCT 2006.

4. 806 patients (13.4%) classified as elderly, >75 years of age.
Background: The REPLACE-2 Trial Transfusion and Major Bleeding are More Frequent in Elderly Patients Undergoing PCI
806 patients (13.4%) classified as elderly, >75 years of age.
p<0.0001
p=0.0001
= Not Elderly, <75
= Elderly, >75
Voeltz MD, Lincoff AM, Feit F, Manoukian SV. Circulation 2005;112(17):II-613.

5. Background: The REPLACE-2 Trial Transfusion and Mortality in PCI
Non-transfused
Transfused
*p<0.0001
Manoukian SV, Voeltz MD, Attubato MJ, Bittl JA, Feit F, Lincoff AM. CRT 2005.

6. 806 patients (13.4%) classified as elderly, >75 years of age.
Background: The REPLACE-2 Trial Transfusion is Associated with Increased Mortality in Elderly Patients Undergoing PCI
806 patients (13.4%) classified as elderly, >75 years of age.
p<0.0001
p=0.0001
= Yes
= No
30-Day Mortality
Voeltz MD, Lincoff AM, Feit F, Manoukian SV. Circulation 2005;112(17):II-613.

7. Background: GUSTO IIb, PURSUIT, PARAGON B Transfusion and 30-Day Mortality in ACS
Rao SV et al. JAMA 2004;292:

8. Adjusted for transfusion propensity
Background: GUSTO IIb, PURSUIT, PARAGON B Transfusion and 30-Day Mortality in ACS
1.0 10
-4.0
Adjusted for transfusion
propensity
Adjusted for baseline
characteristics
Characteristics, bleeding
propensity, transfusion
Propensity, & nadir HCT
3.77 (3.14, 4.52)
3.54 (2.96, 4.23)
3.94 (3.26, 4.75)
(N=24111)
*Transfusion as a time-dependent covariate
Rao SV et al. JAMA 2004;292:

9. Methods: The ACUITY Trial Study Design and Definitions
The ACUITY Trial compared: heparin or enoxaparin + glycoprotein inhibition (H+GPI), bivalirudin + glycoprotein inhibition (BIV+GPI), and bivalirudin monotherapy (BIV) in patients with moderate and high-risk NSTE-ACS.
We evaluated outcomes in patients who received transfusion (non-CABG-related) within 30 days of randomization.
Manoukian SV, Voeltz MD, Feit F et al. TCT 2006.

10. Methods: The ACUITY Trial (N=13819) First Randomization
Moderate and high-risk unstable angina or NSTEMI undergoing an invasive strategy
UFH or
Enoxaparin
+ GP IIb/IIIa
Bivalirudin
Alone R*
Angiography within 72h
Medical
management
PCI
CABG
Moderate-
high risk
ACS
Aspirin in all
Clopidogrel
dosing and timing
per local practice
*Stratified by pre-angiography thienopyridine use or administration
ACUITY Design. Stone GW et al. AHJ 2004;148:764–75.

11. Days from Randomization
Methods: The ACUITY Trial (N=13819) Overall Net Clinical Outcome Composite Endpoint 15
UFH/Enoxaparin + GPI vs. Bivalirudin + GPI vs. Bivalirudin Alone 10
Cumulative Events (%)
Estimate P
(log rank)
11.7%
UFH/Enoxaparin + IIb/IIIa (N=4603)
Bivalirudin + IIb/IIIa (N=4604)
0.89
11.8%
Bivalirudin alone (N=4612)
0.014
10.1% 5 5 10 15 20 25 30 35
Days from Randomization
ACUITY Trial. Stone GW. ACC 2006.

12. Methods: The ACUITY Trial (N=13819) Overall Ischemic Endpoints
PSup = 0.32
PSup = 0.34
PSup = 0.35
PSup = 0.78
ACUITY Trial. Stone GW. ACC 2006.

13. Methods: The ACUITY Trial (N=13819) Overall Bleeding Endpoints
PSup=0.31
PSup<.001
PSup=0.38
PSup<0.0001
ACUITY Trial. Stone GW. ACC 2006.

14. Methods: The ACUITY Trial (N=13819) Second Randomization
Moderate and high-risk unstable angina or NSTEMI undergoing an invasive strategy
Bivalirudin
Alone
UFH or Enoxaparin
Routine upstream GPI in all pts
GPI started in CCL for PCI only R
Medical
management
PCI
CABG
Moderate-
high risk
ACS
Angiography within 72h
Aspirin in all
Clopidogrel
dosing and timing
per local practice
Stone GW et al. AHJ 2004;148:764–75.

15. Methods: The ACUITY Trial (N=13819) Overall Primary Endpoint Measures for Upstream vs. Deferred IIb/IIIa
PNI <0.0001
PSup = 0.93
PNI = 0.044
PSup = 0.13
PNI <
PSup = 0.009
ACUITY Trial. Stone GW. ACC 2006.

16. 319 (2.3%) of 13819 patients had transfusion by 30 days.
Results: The ACUITY Trial (N=13819) Transfusion (non-CABG-related) in ACS
319 (2.3%) of patients had transfusion by 30 days.
Patients with transfusion were (p<0.05):
older, female, non-smokers, and had lower body weight, diabetes, hypertension, impaired creatinine clearance, elevated biomarkers, and high-risk (ST-changes or elevated biomarkers).
more likely to receive pre-treatment with a thienopyridine.
more likely to have a >4h randomization to angiography time.
Transfusion was less frequent for:
Bivalirudin vs. Heparin(s) + GPI (1.6% vs. 2.7%, p<0.0001),
Bivalirudin vs. Bivalirudin + GPI (1.6% vs. 2.6%, p<0.0001).
Transfusion was associated with higher 30-day mortality and ischemic event rates.
Manoukian SV, Voeltz MD, Feit F et al. TCT 2006.

17. Age (median [range], yrs) 72 [38-95] 63 [20-93] <0.0001 Female
Results: The ACUITY Trial (N=13819) Transfusion and Baseline Characteristics
Transfusion
(N=319, 2.3%)
No Transfusion
(N=13500, 97.7%)
P-value
Age (median [range], yrs)
72 [38-95]
63 [20-93]
<0.0001
Female
56.1%
29.5%
Weight (median [IQR], kg)
76 [66-90]
84 [73-95]
Diabetes
43.8%
27.7%
Hypertension
80.9%
66.7%
Current smoker
21.5%
29.3%
0.0027
Prior CABG
22%
17.8%
0.0527
CrCl ≥ 60 ml/min
51%
81.6%
Prior thienopyridine
69.3%
63.8%
0.0478
High-risk (ST / biomarkers)
79.5%
72.1%
0.0041
CK-MB / Troponin+
65.2%
59.3%
0.0382
Random Angiogram >4h
60.8%
53.7%
0.0117
Manoukian SV, Voeltz MD, Feit F et al. TCT 2006.

18. Results: The ACUITY Trial (N=13819) Transfusion by Treatment Strategy
P<0.001
P=ns
ACUITY Trial. Stone GW. ACC 2006.

19. Results: The ACUITY Trial (N=13819) Transfusion, Ischemic Endpoints, and Mortality
P< for all
Manoukian SV, Voeltz MD, Feit F et al. TCT 2006.

20. Results: The ACUITY Trial (N=13819) Transfusion and Myocardial Infarction
P< for all
Manoukian SV, Voeltz MD, Feit F et al. TCT 2006.

21. (D/MI/unplanned revasc) 29.2% 7.1%
Results: The ACUITY Trial (N=13819) Transfusion, Ischemic Endpoints, and Mortality
Transfusion
(N=319, 2.3%)
No Transfusion
(N=13500, 97.7%)
P-value
Death
11.0%
1.3%
<0.0001
Composite ischemia
(D/MI/unplanned revasc)
29.2%
7.1%
Death/MI
26.0%
5.8% MI
18.8%
4.8%
Non-Q wave
13.8%
3.8%
Q wave
5.3%
0.9%
Unplanned revascularization
9.4%
2.3%
Manoukian SV, Voeltz MD, Feit F et al. TCT 2006.

22. Results: The ACUITY Trial Predictors of Transfusion
Risk ratio ± 95% CI
RR (95% CI)
P-value
Age >75 (vs )
Anemia
CrCl <60mL/min
Diabetes
Female gender
High-risk (ST / biomarkers)
Hypertension
Heparin(s) + GPI (vs. Bivalirudin)
1.420 ( )
0.0060
3.764 ( )
<0.0001
2.097 ( )
1.560 ( )
2.233 ( )
1.754 ( )
0.0003
1.457 ( )
0.0241
1.728 ( )
0.0007
Manoukian SV, Voeltz MD, Feit F et al. TCT 2006.

23. Factors associated with an increase in the risk of transfusion:
Conclusion: The ACUITY Trial (N=13819) Transfusion in Patients with ACS
Transfusion is associated with increased 30-day mortality and ischemic event rates in patients with ACS undergoing an invasive strategy.
Bivalirudin results in lower transfusion rates compared to GPI-based strategies.
Factors associated with an increase in the risk of transfusion:
age, female gender, diabetes, hypertension, chronic kidney disease, anemia;
high-risk presentation;
treatment with heparin(s) + GPI.
Knowledge of these factors is important in the assessment of the transfusion risk of, and decision-making for an individual patient.
Minimizing transfusion risk is paramount in order to optimize outcomes in this setting.
Manoukian SV, Voeltz MD, Feit F et al. TCT 2006.