Transfusion is Associated With Increased One-Year

Mortality and Ischemic Events in Patients With ACS: Results

from the ACUITY TrialSteven V. Manoukian, Michele D. Voeltz, Frederick Feit, Sunil V. Rao, Steven

R. Steinhubl, George D. Dangas, Roxana Mehran, and Gregg W. Stone

Emory University School of Medicine, Atlanta, GA; New York University School of Medicine, New York, NY; Duke Clinical Research Institute, Durham, NC;

University of Kentucky, Lexington, KY; Columbia University Medical Center and The Cardiovascular Research Foundation, New York, NY

● The ACUITY Trial randomized 13,819 patients with moderate and high-risk NSTE-ACS.

Moderate-high risk

ACS

An

gio

gra

ph

y w

ith

in 7

2h

Aspirin in allClopidogrel

dosing and timingper local practice

UFH orUFH orEnoxaparinEnoxaparin+ GP IIb/IIIa+ GP IIb/IIIa

BivalirudinBivalirudin+ GP IIb/IIIa+ GP IIb/IIIa

BivalirudinBivalirudinAlone Alone

R*

Medicalmanagement

PCI

CABG

STUDY DESIGN

ACUITY Primary Results – 30 Days

7.3%

5.7%

11.7%

7.7%

11.8%

5.3%

3.0%

10.1%

7.8%

Net clinicaloutcome

Compositeischemia

Major bleeding(non-CABG)

30

da

y e

ve

nts

(%

)

UFH/Enox+ GP IIb/IIIa (N=4603)

Bivalirudin+GP IIb/IIIa (N=4604)Bivalirudin alone (N=4612)

PNI = 0.011 PSup = 0.32

PNI <0.001PSup <0.001

PNI <0.001PSup = 0.015

ACUITY Primary Results – 1 Year

0 1 2

0.96 (0.77-1.18)

HR (95% CI)Hazard ratio

±95% CIHazard ratio

±95% CI

Bivalirudin alone betterBivalirudin alone better Heparin + GPI betterHeparin + GPI better

CompositeIschemia

Mortality

1.06 (0.95-1.17)

P-value

0.67

0.29

● Blood product transfusion is an important

complication in ACS patients treated with potent

antithrombotic and antiplatelet agents.● Transfusion is associated with an increase in

adverse outcomes in ACS, including mortality.● In ACUITY, transfusion was defined as the

administration of any non-CABG related blood

product, including whole blood, packed red blood

cells, platelets, or fresh frozen plasma within 30

days. ● We assessed the relationship between transfusion

and rates of 30-day and 1-year ischemic events

and mortality in patients with ACS in the ACUITY

trial.

BACKGROUND & OBJECTIVES

Baseline Characteristics

Transfusion(N=319)

No Transfusion(N=13,500)

P-value

Age (median [range], yrs) 72 (38, 95) 63 (20, 93) <0.0001

Female 56.1 29.5 <0.0001

Weight (median [IQR], kg) 76 (66, 90) 84 (73, 95) <0.0001

Diabetes 43.8 27.7 <0.0001

Hypertension 80.9 66.7 <0.0001

Hyperlipidemia 61.0 57.1 0.18

Current smoker 21.5 29.3 0.003

Prior MI 33.1 31.3 0.49

Prior PCI 35.6 39.0 0.23

Prior CABG 22.0 17.8 0.05

Baseline CrCl <60 mL/min 49.0 18.4 <0.0001

CKMB/Troponin 65.2 59.3 0.04

Transfusion and 30-Day Event Rates

9.4%

2.3%

18.8%

11.3%

29.5%

4.8%7.1%

1.3%

CompositeIschemia

Death MI (all) UnplannedRevasc

30-d

ay e

ven

t ra

tes

Transfusion (N=319) No Transfusion (N=13,500)

P<0.0001 all

Transfusion and 1-Year Event Rates

21.9%

40.1%

15.1%

3.4%

Composite Ischemia Death

1-ye

ar e

ven

t ra

tes

Transfusion (N=319) No Transfusion (N=13,500)

P<0.0001 both

30-Day Transfusion Rates by Treatment

2.7% 2.6%

1.6%

Transfusion

30-D

ay e

ven

t ra

tes

UFH/Enox+GPI (N=4603) Bivalirudin+GPI (N=4604) Bivalirudin alone (N=4612)

P=0.0003

P=0.70

P=0.0003

P=0.70

Baseline Independent Predictors of 30-Day Transfusion

0 1 2 3 4 5

P -valueRR (95% CI)

Heparin(s) + GPI (vs. Bivalirudin)

Hypertension

High -risk (ST / biomarkers)

Female gender

Diabetes

CrCl <60mL/min

Anemia

Age >75 (vs. 55 -75)

Heparin(s) + GPI (vs. Bivalirudin)

Hypertension

High -risk (ST / biomarkers)

Female gender

Diabetes

CrCl <60mL/min

Anemia

Age >75 (vs. 55 -75)

0.0007

0.0241

0.0003

<0.0001

0.0060

<0.0001

<0.0001

0.0006

1.73 (1.26 -2.38)

1.46 (1.05 -2.02)

1.75 (1.30 -2.37)

2.23 (1.74 -2.87)

1.56 (1.21 -2.01)

2.10 (1.57 -2.80)

3.76 (2.92 -4.86)

1.42 (1.06 -1.91)

0.0007

0.0241

0.0003

<0.0001

0.0060

<0.0001

<0.0001

0.0006

1.73 (1.26 -2.38)

1.46 (1.05 -2.02)

1.75 (1.30 -2.37)

2.23 (1.74 -2.87)

1.56 (1.21 -2.01)

2.10 (1.57 -2.80)

3.76 (2.92 -4.86)

1.42 (1.06 -1.91)

Risk ratio ± 95% CIRisk ratio ± 95% CI

Independent Predictors of 1-Year Mortality

Pre-randomization UFH 1.23 (1.00-1.50)

Diabetes 1.60 (1.34-1.91)

30-day major bleed w/out transfusion 1.80 (1.16-2.80)

30-day transfusion 3.95 (2.92-5.33)

30-day MI 2.55 (1.96-3.32)

ECG changes at baseline 1.68 (1.39-2.02)

CKMB/Troponin+ at baseline 1.56 (1.27-1.92)

History of CAD 1.31 (1.07-1.60)

Male 1.62 (1.31-2.00)

Current Smoker 1.33 (1.11-1.59)

Prior CVA 1.35 (1.10-1.65)

Anemia 1.31 (1.06-1.62)

Age (each 10 years) 1.82 (1.63-2.03)

Pre-randomization UFH 1.23 (1.00-1.50)

Diabetes 1.60 (1.34-1.91)

30-day major bleed w/out transfusion 1.80 (1.16-2.80)

30-day transfusion 3.95 (2.92-5.33)

30-day MI 2.55 (1.96-3.32)

ECG changes at baseline 1.68 (1.39-2.02)

CKMB/Troponin+ at baseline 1.56 (1.27-1.92)

History of CAD 1.31 (1.07-1.60)

Male 1.62 (1.31-2.00)

Current Smoker 1.33 (1.11-1.59)

Prior CVA 1.35 (1.10-1.65)

Anemia 1.31 (1.06-1.62)

Age (each 10 years) 1.82 (1.63-2.03)

0.1 1 10

HR ±95% CI HR (95% CI)

CONCLUSIONS

● Blood product transfusion is

associated with increased rates of

30-day and 1-year composite

ischemic events and mortality in

patients with ACS.

● Transfusion rates are significantly

lower in patients treated with

bivalirudin alone compared to those

treated with heparin plus a GPI.

● Transfusion is a significant

independent predictor of 1-year

mortality in patients with ACS.