“acute coronary syndromes: trials & tribulations" will southern, m.d., m.s. director of...
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“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)