The Trans Radial Intervention and Patient Subsets (I)

The Very Old and The Very Sick Octogenerians, Acute Coronary Syndromes

M.Heigert Landeskrankenhaus Salzburg

Bad Gastein 10.02.2007

2004 2050

Europes Old Age Epidemia

City and country of Salzburg

2004∆ when compared

to 1999

population 524.404 + 2,4%

60 years

(m/f)104.251

(43/57)

+ 15,8 %

75 years 35.495

Current life

expectancy for 60

year males

21,8 + 9,3 %

Current life

expectancy for

60 year females

24,8 + 2,9 %

20 % of Europes population will be over 80 in the year of 2050

Current life expectancy: 82 - 85 years

CHD in Salzburg 2004 - 2006 (without valves): diagnostic

procedures in different age groups

715

3456

2055

640

0

500

1000

1500

2000

2500

3000

3500

<50 50-70 70-80 >80

CAG

39,2 % aller Koronarpatienten >70

Salzburg 2004-2006 valve-diseases pre-op diagnostic

coronary angiogram n=216

9

8286

39

0

10

20

3040

50

60

70

80

90

<50 50-70 >70 >80

pre-op CAG forvalves

57,9% aller Klappenpatienten über 70, 18% über 80

Euro Heart Service on PCI 2006 n=13151

60

78

40

22

0

10

20

30

40

50

60

70

80

male female

>75<75

< 75

> 75

Implications of old age

• Reduced life expectancy

• Reduced physiologic reserves

• Higher comorbidities:– peripheral artery disease– renal insufficiency– diabetes– lung diseases / COAD

• complex CHD

• Higher risks

EHS 2006: risk-profile in the elderly

>75n=2427

<75

n=10725

Med. age 79 61

Hypertension 75% 64%

Hyperlipid. 56% 64%

Smoking 8% 33%

Diabetes 28% 25%

PCI in Elderly: cardiovascular history

EHS 2006

PCI in Elderly: urgency

38%

44%49%

46%

0%

5%

10%

15%

20%

25%

30%

35%

40%

45%

50%

elect. PCI ACS

>75<75

STEMI: 18/18%, NSTEMIEHS 2006 16/12%, UAP 8/6%

Number of diseased vessels

Dsignificantly more 3-VD in the elderly EHS 2006. häufiger

Mean age female LM 3G 2G 1G ns

80,05 ±3,4 69 (50,4%) 11 (8%) 53 (38,6%) 28 (20,4%)

37 (27%) 8 (5,8%)

ACS patients 75 years : n = 137Salzburg 1-9/06:

Salzburg: January - June 2006

Trial of Invasive vs. Medical Therapy in Elderly Patients With Chronic Symptomatic Coronary-Artery Disease (TIME):

A Randomized Trial

Vs. BaselineVs. Baseline InvasivInvasivee

MedicMedicalal

p-p-VValuealue

General healthGeneral health 11.411.4 3.83.8 .008.008Bodily painBodily pain 31.331.3 23.623.6 .12.12VitalityVitality 10.610.6 6.16.1 .16.16Number of angina Number of angina medicationsmedications -1.0-1.0 -0.2-0.2 <.0001<.0001

Duke activity score indexDuke activity score index 7.27.2 5.35.3 .17.17Rose pain scoreRose pain score -1.9-1.9 -1.1-1.1 .008.008Angina pectoris classAngina pectoris class -2.0-2.0 -1.6-1.6 .01.01MACEMACE 19%19% 49%49% <.0001<.0001

148 pts aged 75 years or older with chronic angina of Canadian Cardiac Society class II or more despite treatment with 2 antianginal drugs were assigned to medical therapy and 153 to invasive therapy. Primary end points were quality of life and a composite of death, nonfatal MI, or hospital admission for ACS at 6 months.

148 pts aged 75 years or older with chronic angina of Canadian Cardiac Society class II or more despite treatment with 2 antianginal drugs were assigned to medical therapy and 153 to invasive therapy. Primary end points were quality of life and a composite of death, nonfatal MI, or hospital admission for ACS at 6 months.

Conclusion: Pts aged 75 or older with angina despite standard drug therapy benefit more from revascularization than from medical therapy.Conclusion: Pts aged 75 or older with angina despite standard drug therapy benefit more from revascularization than from medical therapy.

The TIME Investigators, Lancet2001;358:951-957.The TIME Investigators, Lancet2001;358:951-957.

PCI Inhosp. Outcome in old aged patients

EHS 2006

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.

The REPLACE-2 Trial (N=6010):

Trial Design

The REPLACE-2 Trial (N=6010):

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

The REPLACE-2 Trial (N=6010):

Major Bleeding and Mortality in PCI

Feit F, Voeltz MD, Attubato MA, et al. Unpublished.

5,10%

0,20%

6,70%

1,00%

8,70%

1,90%

0,00%

2,00%

4,00%

6,00%

8,00%

10,00%

30-Day Mortality 6-Month Mortality 1-Year Mortality

Major Bleeding

No Major Bleeding

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

The REPLACE-2 Trial (N=6010):

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)

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

The REPLACE-2 Trial (N=6010):

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.

The REPLACE-2 Trial (N=6010):

Mortality with Transfusion in PCI

Non-transfused Transfused

1,9%1,0%0,2%

10,6%

6,3%

13,9%

0,0%

4,0%

8,0%

12,0%

16,0%

30 DayMortality*

6 MonthMortality*

1 YearMortality*

*p<0.0001

Manoukian SV, Voeltz MD, Attubato MJ, Bittl JA, Feit F, Lincoff AM. CRT 2005.

The REPLACE-2 Trial (N=6010):

Predictors of Major Bleeding in PCI

Feit F, Voeltz MD, Attubato MA, et al. Unpublished.

Variable OR 95% CI p-value

Baseline risk factors

Age ≥ 75 1.482 1.01, 2.18 0.045

Gender (Female) 1.535 1.12, 1.10 0.007

Creatinine Clearance 1.008 1.00, 1.01 0.006

Anemia 1.403 1.02, 1.94 0.040

Prior Angina 1.589 1.08, 2.35 0.02

Prior PCI 0.629 0.45, 0.88 0.007

Prior Thienopyridine 0.601 0.39, 0.93 0.023

Peri-procedural risk factors

Treatment Group (Heparin + GPI vs. bivalirudin) 1.969 1.37, 2.84 0.0003

Provisional GPI received 2.679 1.59, 4.51 0.0002

Procedure Duration >1h 2.049 1.22, 3.45 0.007

Time to Sheath Removal >6h 1.614 1.06, 2.45 0.024

Intensive Care Unit stay (days) 1.25 1.18, 1.32 <0.0001

Intra-aortic Balloon Pump 8.7053.43, 22.07 <0.0001

The REPLACE-2 Trial (N=6010):

Predictors of One-Year Mortality in PCI

Voeltz MD, Patel AD, press. Feit F, et al. Am J Cardiol, in

Variable OR (95%CI) p-value

Age ≥ 75 2.28 (1.51, 3.46) 0.0001

Pre-procedural Anemia 2.12 (1.49, 3.13) 0.0002

BMI > 25 (vs. 20-25) 0.61 (0.40, 0.99) 0.007

Pre-procedure LVEF ≤ 50% 2.15 (1.44, 3.21) 0.0002

CHF 3.58 (2.27, 5.65) <.0001

Prior Angina 2.16 (1.25, 3.75) 0.006

Major Bleeding 2.66 (1.44, 4.92) 0.002

MI 2.46 (1.44, 4.20) 0.001

Revascularization 3.30 (1.36, 8.00) 0.008Major

BleedingREPLACE-2

• Intracranial, 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

Concl.

•3/4 of the old age patients >75 years >= 2VD

•2/3 of these patients are only intervened at one vessel (incomplete)

•Even more than in younger patients the PCI-interventions is good for

palliation

•Higher mortality in this high risk group

•Mortality and reinfarctions mainly correlate with the high bleeding risk and

other vascular complications caused at the entry site