Major Bleeding Is Associated With Increased One-Year

Mortality and Ischemic Events in Patients With ACS: Results

From the ACUITY Trial Steven V. Manoukian, Frederick Feit, Steven R. Steinhubl, Michele D. Voeltz,

George D. Dangas, Ramin Ebrahimi, Roxana Mehran, and Gregg W. Stone

Emory University School of Medicine, Atlanta, GA; New York University School of Medicine, New York, NY; University of Kentucky, Lexington, KY; Columbia

University Medical Center and The Cardiovascular Research Foundation, New York, NY; University of California Los Angeles and the Greater Los Angeles VA

Medical Center, Los Angeles, CA

● 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

● Major bleeding is a significant complication of

acute coronary syndromes (ACS).

● Major bleeding is associated with increased 30-

day mortality and ischemic event rates.

● Bivalirudin alone results in lower rates of major

bleeding vs. heparin + GPI strategies.

● We evaluated the impact of major bleeding on 1-

year outcomes in patients with ACS from the

ACUITY Trial.

BACKGROUND & OBJECTIVES

Baseline Characteristics

Major Bleeding(N=645)

No Major Bleeding

(N=13,174)P-value

Age (median [range], yrs) 69 (37, 95) 62 (20, 93) <0.0001

Female 49.3 29.1 <0.0001

Weight (median [IQR], kg) 79 (68, 92) 84 (73, 95) <0.0001

Diabetes 34.5 27.8 0.0002

Hypertension 73.2 66.7 0.0006

Hyperlipidemia 53.3 57.4 0.04

Current smoker 24.8 29.3 0.02

Prior MI 29.1 31.4 0.23

Prior PCI 29.8 39.3 <0.0001

Prior CABG 17.7 17.9 0.90

Baseline CrCl <60 mL/min 37.2 18.2 <0.0001

CKMB/Troponin 68.0 59.0 <0.0001

Major Bleeding and 30-Day Event Rates

7.6%6.9%

1.2%

4.6%

2.2%

7.4%

23.3%

14.6%

Compositeischemia

Death MI (all) UnplannedRevasc

30

da

y e

ve

nts

(%

)Major Bleeding (N=645) No Major Bleeding (N=13,174)

P<0.0001 for all

30-Day Major Bleeding by Treatment

5.7%5.3%

3.0%

Non-CABG Major Bleeding (primary endpoint)

30

da

y e

ve

nts

(%

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

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

P<0.001

Major Bleeding and 1-Year Event Rates

14.9%

3.3%

14.4%

32.7%

Composite ischemia Death

30

da

y e

ve

nts

(%

)Major Bleeding (N=645) No Major Bleeding (N=13,174)

P<0.0001 for all

0

1

2

3

4

5

6

7

8

0 5 10 15 20 25 30 35

Days from Randomization

30-D

ay

Mo

rtal

ity

(%)

Log Rank P–Value <0.0001Log Rank P–Value <0.0001

Patients with major bleedingPatients without major bleeding

7.4%

1.2%

Major Bleeding and 30-Day Mortality

Predictors of 30-Day Major Bleeding

0 1 2 3

P-valueOR (95% CI)Odds ratio ± 95% CIOdds ratio ± 95% CI

Treatment (H+GPI vs. BIV)

PCI

Hypertension

Gender (Female vs Male)

Elevated CKMB/Troponin

ST-segment deviation

CrCl <60mL/min

Anemia

Age >75

Treatment (H+GPI vs. BIV)

PCI

Hypertension

Gender (Female vs Male)

Elevated CKMB/Troponin

ST-segment deviation

CrCl <60mL/min

Anemia

Age >75

<0.0001

0.006

0.04

<0.0001

0.0002

0.0008

<0.0001

<0.0001

<0.0001

1.95 (1.56-2.44)

0.76 (0.62-0.92)

1.24 (1.01-1.52)

1.92 (1.61-2.29)

1.43 (1.19-1.74)

1.35 (1.13-1.61)

1.53 (1.24-1.90)

1.87 (1.54-2.28)

1.64 (1.32-2.02)

<0.0001

0.006

0.04

<0.0001

0.0002

0.0008

<0.0001

<0.0001

<0.0001

1.95 (1.56-2.44)

0.76 (0.62-0.92)

1.24 (1.01-1.52)

1.92 (1.61-2.29)

1.43 (1.19-1.74)

1.35 (1.13-1.61)

1.53 (1.24-1.90)

1.87 (1.54-2.28)

1.64 (1.32-2.02)

Predictors of 1-Year Mortality

Pre-randomization UFH 1.22 (1.00-1.49)

Diabetes 1.62 (1.36-1.93)

30-day revascularization 1.40 (0.92-2.12)

30-day major bleed 2.89 (2.24-3.72)

30-day MI 2.47 (1.87-3.27)

ECG changes at baseline 1.67 (1.39-2.01)

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

History of CAD 1.32 (1.09-1.62)

Male 1.57 (1.28-1.94)

Current Smoker 1.32 (1.10-1.57)

Prior CVA 1.35 (1.10-1.65)

Anemia 1.41 (1.15-1.73)

Age (each 10 years) 1.81 (1.63-2.02)

Pre-randomization UFH 1.22 (1.00-1.49)

Diabetes 1.62 (1.36-1.93)

30-day revascularization 1.40 (0.92-2.12)

30-day major bleed 2.89 (2.24-3.72)

30-day MI 2.47 (1.87-3.27)

ECG changes at baseline 1.67 (1.39-2.01)

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

History of CAD 1.32 (1.09-1.62)

Male 1.57 (1.28-1.94)

Current Smoker 1.32 (1.10-1.57)

Prior CVA 1.35 (1.10-1.65)

Anemia 1.41 (1.15-1.73)

Age (each 10 years) 1.81 (1.63-2.02)

0.1 1 10

HR ±95% CI HR (95% CI)

CONCLUSIONS

● 645 patients (4.7%) had major

bleeding by 30 days.

● Major bleeding is an independent

predictor of one-year mortality and is

associated with increased rates of

ischemic events at one year in

patients with ACS.

● Treatment with bivalirudin

monotherapy significantly lowers

rates of bleeding compared to

treatment with heparin + GPI.