“Acute Coronary Syndromes: Trials & Tribulations"

Will Southern, M.D., M.S.Director of Hospitalist Services

Associate Medical DirectorWeiler Division Hospital of Montefiore Medical Center

DIVISION OF GENERAL INTERNAL MEDICINE

In 25 Minutes…

● Update the most recent studies…how should they change my practice?

● How long to continue antiplatelet therapy for drug-eluting stents?

● Can I trust the Troponin? When is it safe to discharge?

● Inpatient stress test or not? Which one?

In 25 Minutes…

● Update the most recent studies…how should they change my practice?

● How long to continue antiplatelet therapy for drug-eluting stents?

● Can I trust the Troponin? When is it safe to discharge?

● Inpatient stress test or not? Which one?

N-acetylcysteine for prevention of contrast-induced nephropathy in

primary angioplasty

Standard dose NAC(600mg IV before + 600mg PO bid x 48hrs)

vs.

High dose NAC(1200mg IV before + 1200mg PO bid x 48hrs)

vs.

Control

Marenzi N Engl J Med 2006;354:2773-82

N-acetylcysteine for prevention of contrast-induced nephropathy in

primary angioplasty

● Not blinded

● Outcomes:

1. Contrast Nephropathy: 25% increase in creatinine within 72hrs

2. Mortality, ARF (dialysis), Intubation

Marenzi N Engl J Med 2006;354:2773-82

Marenzi G et al. N Engl J Med 2006;354:2773-2782

Contrast-Induced Nephropathy Stratified According to Creatinine Clearance and Ejection Fraction

Incidence of contrast-nephropathy

33

15

8

0

5

10

15

20

25

30

35

% with outcome

Contrast Nephropathy

Placebo

Standard Dose

High Dose

Marenzi N Engl J Med 2006;354:2773-82

P < 0.001

Clinical Outcomes

18

7

5

0

2

4

6

8

10

12

14

16

18

% with outcome

Composite*

Control

Standard Dose

High Dose

Marenzi N Engl J Med 2006;354:2773-82

*Mortality, Dialysis, Mech Ventilation

P = 0.001

Clinical Outcomes

5

21

8

2 2

11

43

0

2

4

6

8

10

12

% with outcome

ARF requiringHD

Intubation In-hosp Mort

Control

Standard Dose

High Dose

Marenzi N Engl J Med 2006;354:2773-82

P = 0.04 P = 0.007

P = 0.02

Early Invasive vs. Selectively invasive strategy in NSTEMI

● 1200 patients with elevated Troponin T and either ECG changes or known history of CAD

● Early invasive strategy: Catheterization and PCI within 24-48 hours

● Selectively invasive strategy: Catheterization if failed optimal medical therapy or clinically significant ischemia on non-invasive testing

De Winter et al NEJM 2005 353:1095-104

22.721.2

15.0

10.0

2.5 2.5

7.4

10.9

0

5

10

15

20

25

Composite* MI Death Rehosp

Early Invasive

Selectively Invasive

Early Invasive vs. Selectively invasive strategy in NSTEMI

De Winter et al NEJM 2005 353:1095-104*Death, MI or Rehospitalization

Meta-analysis of early-invasive vs. selectively invasive strategy for NSTEMI

12.2

14.4

5.5 6.07.3

9.4

0

2

4

6

8

10

12

14

16

Composite* Death MI

Early Invasive

Selectively Invasive

Mehta et al JAMA 2005;293:2908-17*Death or MI

Study showing non-inferiority of selective approach had:

● Included slightly lower risk population

● Optimal Medical therapy included: – ASA (all)– LMWH (all) – Intensive Statin (>90%) – Clopidogrel (61 & 49%) – IIb-IIIa inhibitors during PCI

Selective Catheterization is a defensible option:

● Lower risk patients

● Optimal Medical Therapy: ASA, LMWH, Clopidogrel, Intensive Statin Therapy

● Early non-invasive study

In 25 Minutes…

● Update the most recent studies…how should they change my practice?

● How long to continue antiplatelet therapy for drug-eluting stents?

● Can I trust the Troponin? When is it safe to discharge?

● Inpatient stress test or not? Which one?

In-Stent Restenosis• Scar tissue under

endothelial lining

• 22-32% at 6 months with Bare Metal Stents (BMS)

• About half of angiographic restenosis results in a clinical event:

• 7% Non-fatal MI• 1% Death

Steinberg et al Am J Cardiol 100(7) 1109-1113

Thrombotic Stent Closure

• 75% non-fatal MI

• 25% death

• Dual antiplatelet therapy: ASA plus Clopidogrel or Ticlopidine

Drug-eluting stents (DES) vs. bare metal stents (BMS)

31.7

10.5

16.6

6.2

19.9

10.1

0

5

10

15

20

25

30

35

Restenosis Revascularization Events

BMS

DES

Copyright ©2006 BMJ Publishing Group Ltd.

Roiron, C et al. Heart 2006;92:641-649

Mortality for DES vs. BMS

Copyright ©2006 BMJ Publishing Group Ltd.

Roiron, C et al. Heart 2006;92:641-649

Mortality for DES vs. BMS

Spaulding C et al. N Engl J Med 2007;356:989-997

Survival Curves for Patients with and without Diabetes

Stent Thrombosis in the Pooled

Population According to Stent Type and the

Duration of Dual Antiplatelet Therapy

Kastrati A et al. N Engl J Med 2007;356:1030-1039

Early and late events

7.2

12.0

0.0

2.0

4.0

6.0

8.0

10.0

12.0

Cardiac Events

Months 0-6

DES

BMS

9.3

7.9

4.9

1.3

0123456789

10

CardiacEvents

CV Deathor MI

Months 7-18

DES

BMS

Pfisterer et al JACC 2006;48:2584-91Kaiser et al Lancet 2005;366:921-9

Recommendations:

● Consider BMS in patients who may not be able to comply with long term Clopidogrel

● Consider BMS in patients with Diabetes

Recommendations:

● JACC editorial (2007): Dual therapy (Clopidogrel & ASA) until issue of duration is resolved

● ACC advisory (2007) Dual therapy for 1 year

● Probably should continue Clopidogrel beyond 1 year in patients who have a low risk of bleeding (Up To Date)

In 25 Minutes…

● Update the most recent studies…how should they change my practice?

● How long to continue antiplatelet therapy for drug-eluting stents?

● Can I trust the Troponin? When is it safe to discharge?

● Inpatient stress test or not? Which one?

Prognostic value of TroponinsIs the problem solved ?

● Very sensitive for Acute MI (100 %)

● Not so sensitive for Unstable Angina (36 %)

● NPV for events @ 30 days impressive (99.6%)

Hamm et al NEJOM 1997;337:1648-53

Event rates in Negative Troponins

0.5 0.3

3.2

5.2 4.8

11.7

0

2

4

6

8

10

12

Percent with

Event

Polanczyk 72-hour

Hamm 30-day

Newby 30-day

Sayre 60-day

Sanchis 6-Month

Hillis 31-Mo

Event rates in Negative Troponins

0.5 0.3

3.2

5.2 4.8

11.7

0

2

4

6

8

10

12

Percent with

Event

Polanczyk 72-hour

Hamm 30-day

Newby 30-day

Sayre 60-day

Sanchis 6-Month

Hillis 31-Mo

Polanczyk predictors: Male,CP worse, known CAD, EKG changes

Event rates in Negative Troponins

0.5

3.7

0.3

3.2

5.2 4.8

11.7

0

2

4

6

8

10

12

Percent with

Event

Polanczyk 72-hour

Hamm 30-day

Newby 30-day

Sayre 60-day

Sanchis 6-Month

Hillis 31-Mo

Polanczyk predictors: Male,CP worse, known CAD, EKG changes

TIMI Risk Score

● Age > 65● 3 cardiac risk factors● Known CAD● ST deviation on ECG● 2 anginal episodes in last 24 hours● Elevated Cardiac markers● Recent use of ASA

30-day Event rates by TIMI risk score

2.1 510.1

19.5 22.1

39.245

100

0

10

20

30

40

50

60

70

80

90

100

% with

Event

0 1 2 3 4 5 6 7

Pollack et al Acad Emerg Med 2006 13:13-18

30-day Event rates by TIMI risk score

2.1 510.1

19.5 22.1

39.245

100

0

10

20

30

40

50

60

70

80

90

100

% with

Event

0 1 2 3 4 5 6 7

Pollack et al Acad Emerg Med 2006 13:13-18

Clinical Assessment after ROMI

● Quality of Symptoms● 2 or more episodes in last 24 hours● Age > 65● Insulin Dependent DM● Prior intervention● Alternative diagnosis

Sanchis JACC 2005 46(3):443-9

Clinical combinations that may have a good prognosis

● Prolonged Chest Pain and normal Troponin

● Normal ECG and normal Troponin in a young, non-diabetic patient without prior CAD.

● Normal Troponin and atypical symptoms in young, non-diabetic patient without prior CAD.

In 25 Minutes…

● Update the most recent studies…how should they change my practice?

● How long to continue antiplatelet therapy for drug-eluting stents?

● Can I trust the Troponin? When is it safe to discharge?

● Inpatient stress test or not? Which one?

Diagnostic Characteristics of Non-invasive testing modalities

68

7779

73

88

77 76

8891

82

50

55

60

65

70

75

80

85

90

95

100

StressECG

Thallium SPECT StressEcho

PET

Sens

Spec

Outcomes after negative test

0.16 0.512.0 0 0 2.00

10

20

30

40

50

60

70

80

90

100

Amsterdam(2002)

Polanczyk (1998)

Lewis (1999)

Bholasingh(2003)

30 day

6 Month

Outcomes after negative test

0.16 0.512.0 0 0 2.00

10

20

30

40

50

60

70

80

90

100

Amsterdam(2002)

Polanczyk (1998)

Lewis (1999)

Bholasingh(2003)

30 day

6 Month

Non-diagnostic Studies

64

23

71

20

38 39

93

00

10

20

30

40

50

60

70

80

90

100

Amsterdam(2002)

Polanczyk (1998)

Lewis (1999)

Bholasingh(2003)

% Negative

% Non-diagnostic

Contraindications to Stress ECG testing

● LBBB (Vasodilator pharmachologic)● LVH● Digoxin● ST abnormalities● Paced rhythm● Pre-excitation● Can’t exercise: (ie won’t make 85% predicted

MHR)

Stress ECG, unless…

Baseline ECG Abnormalities (except LBBB):

• Exercise perfusion imaging

• Exercise Echocardiography

Unable to exercise:• Pharmacologic perfusion

imaging or echocardiography

LBBB:• Adenosine or

Dipyridamole perfusion imaging