Michael A. Nelson, MD1

Michele D. Voeltz, MD1

Frederick Feit, MD 2

A. Michael Lincoff, MD 3

Steven V. Manoukian, MD1

1Emory University School of Medicine2 New York University School of Medicine

3 Cleveland Clinic Foundation

Elderly Patientswith Major Bleeding or Need for

Transfusion Complicating Percutaneous Coronary Intervention

Have an Increased Risk of30-Day and 1-Year Mortality

Presenter Disclosure Information

• Michael A. Nelson: NoneMichael A. Nelson: None

• Michele D. Voeltz: NoneMichele D. Voeltz: None

• Frederick Feit: The Medicines Co.-Frederick Feit: The Medicines Co.-Consultant (significant)

• A. Michael Lincoff: The Medicines Co.-Research Support A. Michael Lincoff: The Medicines Co.-Research Support (significant), Honoraria (modest)(significant), Honoraria (modest)

• Steven V. Manoukian: The Medicines Co.-Research Support, Steven V. Manoukian: The Medicines Co.-Research Support, Consultant, Speaker (modest), sanofi-aventis/BMS: Consultant Consultant, Speaker (modest), sanofi-aventis/BMS: Consultant (modest)(modest)

Elderly Patients with Major Bleeding or Transfusion:

Background

• Elderly patients have an increased risk of major bleeding and transfusion when undergoing percutaneous coronary intervention (PCI).

• Despite these risks, the effect of major bleeding and transfusion on mortality in the elderly is unknown.

• We evaluated outcomes in elderly patients undergoing PCI from the REPLACE-2 Trial.

6010

Urgent or

electivePCI

patients

6010

Urgent or

electivePCI

patients

AspirinClopidogrel

Stent

AspirinClopidogrel

Stent

29992999

30113011 HeparinHeparin65 U/kg65 U/kgHeparinHeparin65 U/kg65 U/kg

Endpoints

30-dayDeathMIRevascHemorrhage

Economics6, 12m follow up

Endpoints

30-dayDeathMIRevascHemorrhage

Economics6, 12m follow up

BivalirudinBivalirudin

Provisional GPIIb/IIIaProvisional GPIIb/IIIaBivalirudinBivalirudin

Provisional GPIIb/IIIaProvisional GPIIb/IIIa

AbciximabAbciximaboror

EptifibatideEptifibatide

AbciximabAbciximaboror

EptifibatideEptifibatide

Lincoff AM, et al. JAMA 2003; 289: 853-863.

Background: The REPLACE-2 Trial

Trial Design

Background: The REPLACE-2 Trial

Primary Endpoint at 30 Days

6.2%

1.4%

4.1%

7.0%

2.4%

10.0%

0.4%

9.2%

1.2%0.2%

Quadruplecomposite

Death MI UrgentRevasc

MajorBleeding

Heparin + GPIIb/IIIa (N=3008)

Bivalirudin (N=2994)

6.2%

1.4%

4.1%

7.0%

2.4%

10.0%

0.4%

9.2%

1.2%0.2%

Quadruplecomposite

Death MI UrgentRevasc

MajorBleeding

Heparin + GPIIb/IIIa (N=3008)

Bivalirudin (N=2994)

% of patients% of patients

p = 0.324p = 0.324 p = 0.255p = 0.255 p = 0.430p = 0.430 p = 0.435p = 0.435 p < 0.001p < 0.001

Lincoff AM, et al. JAMA 2003; 289: 853-863.

Major bleeding

• Intracranial, intraocular, or retroperitoneal• Observed bleed with fall in Hgb >3g/dL• No observed bleed with fall in Hgb >4g/dL• Transfusion 2 units PRBC or whole blood

0.2%

1.2% 0.9%

2.9%

1.7%

5.3%

0.0%

1.0%

2.0%

3.0%

4.0%

5.0%

6.0%

30 Days 6 Months 1 Year

Background: The REPLACE-2 Trial

Mortality by Age

= Elderly, >75 (N=805)

= Not Elderly, <75 (N=5196)

p<0.0001 p=0.0001p<0.0001

Mo

rtal

ity

Voeltz MD, et al. Circulation 2005;112(17):II-613.

2.7%

6.7%

1.7%

5.0%

0.0%

1.0%

2.0%

3.0%

4.0%

5.0%

6.0%

7.0%

Major Bleeding Transfusion

Background: The REPLACE-2 Trial

Bleeding and Transfusion by Age

p<0.0001 p<0.0001

Voeltz MD. et al. Circulation 2005;112(17):II-613.

= Elderly, >75 (N=805)

= Not Elderly, <75 (N=5196)

Elderly Patients with Major Bleeding or Transfusion:

Hypothesis

• Elderly patients with major bleeding or transfusion complicating PCI have an increased risk of mortality.

Elderly Patients with Major Bleeding or Transfusion:

Methods• We reviewed the REPLACE-2 Trial in order to evaluate the

impact of major bleeding and transfusion on the risk of 30-day, 6-month and 1-year mortality in elderly patients undergoing PCI.

• Elderly patients were defined as > 75 years of age.

• Major Bleeding (30-Days) was defined as: – Intracranial, intraocular, or retroperitoneal hemorrhage – Overt blood loss with drop in Hgb >3g/dL– Any decrease in Hgb >4g/dL– Transfusion of >2 pRBC’s or whole blood

• Transfusion (30-Days) was defined as any transfusion of pRBC’s or whole blood.

Results:

Baseline Characteristics by Age

 

Elderly>75 years (N=805)

Not Elderly75 years (N=5196)

p-value

Age (Mean, Years) 79.3 60.0

Women 39.3% 23.5% <0.01

Caucasian 94.3% 92.2% 0.04

Prior CABG 23.9% 17.5% <0.01

CVA 3.9% 2.1% 0.01

Hypertension 75.4% 65.7% <0.01

CHF 13.3% 6.0% <0.01

Weight (kg) 77.5 89.0 <0.01

Body Mass Index (kg/m2) 27.3 30.0 <0.01

Prior MI 32.6% 37.7% 0.01

Tobacco Use (last 1y) 6.1% 29.7% <0.01

Baseline Hemoglobin (g/dL) 12.9 13.8 <0.01

Creatinine Clearance (cc/min) 57.4 100.2 <0.01

2.2%

13.0%

3.6%

14.8%

5.8%

16.7%

0.0%

2.0%

4.0%

6.0%

8.0%

10.0%

12.0%

14.0%

16.0%

18.0%

20.0%

30 Days 6 Months 1 Year

Results:

Mortality with Major Bleeding by Age

= Elderly, >75 (N=54)

= Not Elderly, <75 (N=139)

p<0.01 p<0.02p<0.01

Mo

rtal

ity

Nelson MA, et al. AHA 2006.

2.3%

15.0%

6.0%

20.0%

8.5%

25.0%

0.0%

5.0%

10.0%

15.0%

20.0%

25.0%

30.0%

30 Days 6 Months 1 Year

Results:

Mortality with Transfusion by Age

= Elderly, >75 (N=40)

= Not Elderly, <75 (N=86)

p<0.02 p<0.02p<0.02

Mo

rtal

ity

Nelson MA, et al. AHA 2006.

0.4%

13.0%

2.0%

14.8%

4.5%

16.7%

0.0%

5.0%

10.0%

15.0%

20.0%

30 Day 6 Month 1 Year

Results:

Mortality Among Elderly by Bleeding Status

= Elderly, Major Bleed (N=54)

= Elderly, No Major Bleed (N=751)

p<0.01 p<0.01

Mo

rtal

ity

p<0.01

Nelson MA, et al. AHA 2006.

0.5%

15.0%

2.0%

20.0%

4.2%

25.0%

0.0%

5.0%

10.0%

15.0%

20.0%

25.0%

30 Day 6 Month 1 Year

Results:

Mortality Among Elderly by Transfusion Status

= Elderly, Transfusion (N=40)

= Elderly, No Transfusion (N=765)

p<0.0001 p<0.0001

Mo

rtal

ity

p<0.0001

Nelson MA, et al. AHA 2006.

Results:

Baseline Characteristics Among Elderly by Bleeding Status

Elderly with Major Bleeding (N=54)

Elderly without Major Bleeding (N=751)

p-value

Women 53.7% 38.3% 0.03

Prior MI 46.2% 31.7% 0.03

CHF 22.2% 12.6% 0.04

Baseline Anemia 56% 41% 0.03

Baseline Hemoglobin (g/dL) 12.1 12.9 <0.01

Creatinine Clearance (cc/min) 53 58 0.03

Weight (kg) 76.2 77.6 ns

Body Mass Index (kg/m2) 27.8 27.3 ns

Prior Diabetes Mellitus 31.5 28.8 ns

Prior CABG 31.5% 23.4% ns

CVA 5.7% 3.7% ns

Hypertension 77.8% 75.3% ns

Caucasian 88.9% 94.7% ns

Tobacco Use (last 1y) 3.8% 6.3% ns

Elderly Patients with Major Bleeding or Transfusion:

Conclusions

• Elderly patients undergoing PCI have an increased risk of major bleeding, transfusion, and mortality, compared to younger patients.

• Among patients with major bleeding or transfusion, the elderly have an increased risk of mortality.

• Among the elderly, major bleeding or transfusion is associated with an increased risk of mortality.

• Knowledge of these findings is important in the care of elderly patients undergoing PCI.

Nelson MA, et al. AHA 2006.