risk stratification in ua and nstemi: why and how?
TRANSCRIPT
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RISK STRATIFICATION IN UA RISK STRATIFICATION IN UA AND NSTEMI :WHY AND HOW?AND NSTEMI :WHY AND HOW?
-Dr.DEV PAHLAJANI MD,FACC,FSCAI
HOD INTERVENTIONAL CARDIOLOGY BREACH CANDY HOSPITAL, CONS.CARDIOLOGIST B.NANAVATI HOPSITAL MUMBAI
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ACS is an Important Manifestation of Atherothrombosis1
1. Cannon CP. J Thromb Thrombolysis 1995; 2: 205–218.
Antithrombotictherapy
Stable angina
UA Non-Q-wave MI
Thrombolysisprimary PCI
Q-wave MI
Minutes– hours
Days–weeks
STEMIUA/NSTEMIAtherothrombosisNew term
Old term
Plaquerupture
UA=unstable angina; NSTEMI=non-ST-segment elevation myocardial infarction; PCI=percutaneous coronary intervention
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Our current understanding of unstable coronary syndromes is that they include a spectrum of disease and begin with a coronary plaque rupture1
The degree of thrombus occlusion determines the severity of the clinical syndrome, with total occlusion in ST-segment elevation MI (STEMI) or severe (90%) stenosis in patients with non-ST-segment elevation MI (NSTEMI) or unstable angina (UA)1
In addition, it is worthwhile to note that 99% of all plaque ruptures are clinically silent. A small degree of rupture leads to a small thrombus, which heals over, leading to the progression of a plaque1
This current understanding of how atherosclerosis progresses emphasizes the key role that acute and chronic antithrombotic therapy plays in all patients with unstable coronary syndromes1
• Reference• 1. Cannon CP. J Thromb Thrombolysis 1995; 2: 205218.
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Acute coronary syndromes: Prognostic spectrum
Unstable angina• New onset exertional angina• Progressive angina• Rest pain without EKG changes• Rest pain with EKG changes• Rest pain troponin+ Non ST elevation MI (NSTEMI) Acute ST segment elevation MI
Coronary occlusion & short term death Least Greatest
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Objectives of stratification
Can We Identify Patients At Low, Intermediate And High Risk Of Short
Term And Long Term Macce?
Will It Help To Guide Treatment For Better Outcome?
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The TIMI unstable angina risk score
7 possible risk factors:• Age >= 65 years• Prior known CAD• >= 3 coronary risk factors ( HTN, Hchol, FH, DM, current smoker)• Aspirin use within 7 days• ST segment deviation• >= 2 episodes of angina within 24 hours• Abnormal cardiac markers (MB or T)
Low risk = 0-2 risk factorsIntermediate risk = 4-3 risk factors
High risk = 5-7 risk factorsAntman EM et al: JAMA 2000;284:835-42
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PURSUIT SCORE(0–18)Age, separate points for enrolment diagnosisDecade [UA (MI)]
50 18 (11) 60 19 (12) 70 11 (13) 80 12 (14)
Sex Male 1
Female 0Worst CCS-class in previous 6 weeks
No angina or CCS I/II 0 CCS III/IV 2
Signs of heart failure 2ST-depression on presenting ECG 1
Eur Heart J (May 2005) 26 (9):865-872.
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GRACE(0–258)Age (years)
<40 0 40–49 18 50–59 36 60–69 55 70–79 73
≥80 91
Heart rate (bpm)
<70 0 170–89 7
190–109 13 110–149 23 150–199 36
>200 46
Systolic BP (mmHg)
<80 63 180–99 58
100–119 47 120–139 37 140–159 26 160–199 11
>200 0Creatinine (mg/dL)
0.0- 0.39 2 0.4–0.79 5 0.8–1.19 8 1.2–1.59 11 1.6–1.99 14 0.2–3.99 23
>4 31
Killip class
Class I 0Class II 21Class III 43Class IV 64
Cardiac arrest at admission 43
Elevated cardiac markers 15
ST-segment deviation 30
Eur Heart J (May 2005) 26 (9):865-872.
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TIMI, PURSUIT, and GRACE risk scores: sustained prognostic value
and interaction with revascularization in NSTE ACS‐
Pedro de Araújo Gonçalves, Jorge Ferreira,
Carlos Aguiar andRicardo Seabra-Gomes
Eur Heart J (May 2005) 26 (9):865-872.
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Objective
• Compare the prognostic value • Ability to predict benefit from myocardial
revascularization performed during initial hospitalization
Eur Heart J (May 2005) 26 (9):865-872.
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Study Endpoint• Follow up
1 year OR Until major event
• Endpoint All-cause mortality OR Non-fatal MI
• Analysis 30 days 1 year.
Eur Heart J (May 2005) 26 (9):865-872.
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Interaction between the admission score and the prognostic impact of myocardial
revascularization performed during initial hospital stay.
Eur Heart J (May 2005) 26 (9):865-872.
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Comparison of the predictive accuracy of the risk scores
30 days 1 yearΔ P-value Δ P-value
PURSUIT vs. TIMI 0.064 0.288 0.044 0.319
GRACE vs. PURSUIT 0.057 0.332 0.086 0.04
GRACE vs. TIMI 0.121 0.054 0.130 0.004
Eur Heart J (May 2005) 26 (9):865-872.
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Conclusions RSs developed from
Databases of clinical trials (PURSUIT and TIMI) or Registries (GRACE)
• At 30 days the risk stratification by all 3 scores for patients with NSTE ACS‐
has fair to good discriminatory accuracy in predicting major adverse cardiac events at both 30 days and 1 year.
• The GRACE RS was the best for predicting the risk of death or MI at 1 year after admission.
Eur Heart J (May 2005) 26 (9):865-872.
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The TIMI unstable angina risk score
7 possible risk factors:• age >= 65 years• >= coronary risk factors (like HTN, Hchol, FH, DM, current
smoker)• Aspirin use within 7 days• ST segment deviation• >= 2 episodes of angina within 24 hours• Abnormal cardiac markers (MB or T)
Low risk= 0-2 risk factorsIntermediate risk= 3-4 risk factorsHigh risk = 5-7 risk factors
Antman EM et al. JAMA 2000:284:835-42
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Prognostic value of recurrent ischemia in ACS
Armstrong PW et al. Circulation 1998:98:1860-1868
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Troponin T and ST segment depression are independent predictors of adverse cardiac
events at FU in ACSUnivariate OR( 95% Cl) Multivariate OR (95% Cl)
ST segment depression
1 mm 1.56[1.02-2.40] 1.34[0.86-2.09]
2mm 2.64 [1.57-4.44] 1.91 [1.10-3.32]
Troponin T
0.01-0.047 ng/ml 2.45 [1.25-4.82] 2.43 [1.22-4.85]
0.048-0.277 ng/mg 3.23[1.89-5.16] 3.18 [1.83-5.53]
0.278- 8.37 ng/ml 3.91 [2.32-6.61] 3.86 [2.24-6.66]
Kaul et al.JACC 2002
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11.8
20.3
12.816.1
19.5
30.6
0
5
10
15
20
25
30
35
Low 0-2 Intermed. 3-4 High 5-7
Dea
th/M
I/A
CS
Reh
osp
(%
)
TIMI Risk Score
CONS
TIMI Risk Score: 1oEP at 6 mos
% of Pts: 25% 60% 15%
INV
OR=0.75OR=0.75CI (0.57, 1.00)CI (0.57, 1.00)
OR=0.55OR=0.55CI (0.33, 0.91)CI (0.33, 0.91)
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TACTICS TIMI 18Troponin T : Primary endpoint
Death / MI / rehospitalization for ACS at 6 months
30
25
20
15
10
5
0 TnT negative TnT positive
Conservative InvasiveOR = 0.53 p<0.001Interaction p<0.001
TnT cut point = 0.001ng/ml (54 % of patientswere Troponin T positive)
P=NS
Inci
denc
e (%
)
14.516.9
24.5
14.2
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TnT +, CONS
TnT +, INVTnT -, CONS
TnT -, INV
TACTICS-TIMI 18: Invasive vs. Cons. Troponin T >0.01 ng/dl
Primary Endpoint: Death/MI/Rehosp ACS
24.2%
14.8%
Morrow DA, et al. JAMA 2001;286:2405-2412.
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Through 14 days in the un fractionated heparin (UFH) and enoxaparin (ENOX) treatment groups in the pooled (TIMI) 11B
and (ESSENCE) trial populations, with patients stratified by TIMI risk score
J Am Coll Cardiol. 2003;41(4s1):S89-S95.
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High TIMI score is associated with coronary thrombus in ACS
Subanalysis of PRISM-PLUS (n=1491)
D.A Morrow et al, AHA
2001
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Evaluation of B-Type Natriuretic Peptide for Risk Assessment in Unstable Angina/Non-ST-
ElevationMyocardial Infarction
B-Type Natriuretic Peptide and Prognosis in Tactics-TIMI 18
David A. Morrow, MD, MPH, James A. de Lemos, MD, Marc S. Sabatine, MD, MPH, Sabina A. Murphy, MPH, Laura A. Demopoulos, MD, Peter M. Dibattiste, MD,
Carolyn H. McCabe, BS, C. Michael Gibson, MD, MS, Christopher P. Cannon, MD, Eugene Braunwald, MD
Morrow DA et al. J Am Coll Cardiol. 2003;41:1264-72.
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Mortality Risk Stratified by B-Type Natriuretic Peptide Levels Over Range of 40 to 160 pg/ml: UA/NSTEMI
1.7 1.9
3.6
7.1
10.9 11.1
0
2
4
6
8
10
12
14
6 M
onth
Mor
talit
y (%
)
BNP (pg/ml) 40 >40- 80>80- 100
>100- 120 >120- 160 >160
BNP Threshold >40 >80 >100 >120 >160
% Positive - 38% 19% 14% 11% 7%
OR - 1.9 3.7 4.0 3.7 2.4
X2 - 3.8 13.8 16.2 14.1 5.9 Morrow DA et al. J Am Coll Cardiol. 2003;41:1264-72.
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Combination of cTnI, CRP, BNP in ACS
Sabatine MS et al. Circulation. 2002;105:1760-3.
OPUS-TIMI 16
# of Elevated Cardiac Biomarkers
30-D
ay M
orta
lity
Rela
tive
Risk N=450
P = 0.014
N = 67 150 155 78
0
1
2
3
4
5
6
0 1 2 3
TACTICS-TIMI 18
# of Elevated Cardiac Biomarkers
30-D
ay M
orta
lity
Rela
tive
Risk
N=1635 Validation
P < 0.0001
N = 504 717 324 90
0
2
4
6
8
10
12
14
0 1 2 3
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Conclusions
• UA and NSTEMI Patients have varied anatomy and pathology
• Need to be stratified to determine urgency and modality of treatment either invasive or conservative
• Simple bed side score like TIMI score can stratify patients in low, intermediate and high risk patients
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Multimarker Data
72.0
16.0
6.8 5.90
10
20
30
40
50
60
70
80P
erce
nt o
f C
ases
0 1 2 3
Number or Markers Positive
Kontos MC, Garg R, Anderson FP, Roberts CS, Tatum JL, Ornato JP, Jesse RL. A multimarker strategy predicts short- and long-term mortality n patients admitted for the exclusion of myocardial infarction. J Am Coll Cardiol 2005;45(3):217A.
N= 34613461
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Risk of Death or MI at 30 Days Stratified by BNP and cTnI: UA/NSTEMI
0.71.4
2
6.4
4.5
5.4
7.57.9
0
2
4
6
8
10
cTnI NEGP=0.004
cTnI POSP<0.001
cTnI NEGP=0.008
cTnI POSP=0.4
%
BNP >80 BNP <80
Death Death/MI
Morrow DA et al. J Am Coll Cardiol. 2003;41:1264-72.
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30-day and 1-year endpoint rates for PURSUIT score
Eur Heart J (May 2005) 26 (9):865-872.
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30-day and 1-year endpoint rates for the TIMI score.
Eur Heart J (May 2005) 26 (9):865-872.
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30-day and 1-year endpoint rates for the GRACE score.
Eur Heart J (May 2005) 26 (9):865-872.
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Through 30 days in the heparin alone and tirofiban plus heparin treatment groups in (PRISM-PLUS), with
patients stratified by (TIMI) trial risk score
J Am Coll Cardiol. 2003;41(4s1):S89-S95.
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Through six months in the invasive (INV) and conservative (CONS) treatment strategy arms in (TACTICS TIMI)-18 trial, with patients stratified
by TIMI risk score
J Am Coll Cardiol. 2003;41(4s1):S89-S95.
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ST-Segment Elevation
Acute Evaluation of ACS
Chest Pain or Short of Breath
Unstable Angina
ST-Segment Depression
– + +
Presentation
ECG
Diagnosis
Adapted from Braunwald E, et al. Available at: Adapted from Braunwald E, et al. Available at: http://www.americanheart.org/downloadable/heart/1022188973899unstable_may8.pdf.http://www.americanheart.org/downloadable/heart/1022188973899unstable_may8.pdf.
Adapted from Antman EM, et al.Adapted from Antman EM, et al. Circulation Circulation.2004 Aug 31;110(9):e82-292..2004 Aug 31;110(9):e82-292.
Adapted from Braunwald E, et al. Available at: Adapted from Braunwald E, et al. Available at: http://www.americanheart.org/downloadable/heart/1022188973899unstable_may8.pdf.http://www.americanheart.org/downloadable/heart/1022188973899unstable_may8.pdf.
Adapted from Antman EM, et al.Adapted from Antman EM, et al. Circulation Circulation.2004 Aug 31;110(9):e82-292..2004 Aug 31;110(9):e82-292.
Normal
Blood Marker Panel
Acute MI
–+
Rule-Out
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Clinical Utilization of Cardiac Troponin and Natriuretic Peptides in ACS and CHF
Consultant Cardiologist and Chief, Division of Nutrition and Preventive Medicine Clinical Professor, Oakland University School of Allied
Health Sciences, William Beaumont Hospital, Royal Oak, Michigan, USA
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Changes in Focus on Heart FailureTroponin i levels predict the risk of mortality in ua/nstemi
Troponin i levels predict the risk of mortality in ua/nstemi
1.01.0
1.71.7
3.43.4
3.73.7
6.06.0
7.57.5
00
22
44
66
88
0 to <0.40 to <0.4 0.4 to <1.00.4 to <1.0 1.0 to <2.01.0 to <2.0 2.0 to <5.02.0 to <5.0 5.0 to <9.05.0 to <9.0 >9.0>9.0
831 174 148 134 6750
Cardiac Troponin I (ng/ml)Risk Ratio 1.0 1.8 3.5 3.9 6.2 7.8AntmanN Engl J Med. 335:1342, 1996
Cardiac Troponin I (ng/ml)Risk Ratio 1.0 1.8 3.5 3.9 6.2 7.8AntmanN Engl J Med. 335:1342, 1996
Mor
talit
y at
42
Day
s (%
of p
atien
ts)
Mor
talit
y at
42
Day
s (%
of p
atien
ts)
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BNP Elevation in ACS
• Pre-existing or concurrent HF• Large zone of myocardial ischemia
– Left main disease– Multivessel disease
• Large zone of infarction• Delayed presentation• Renal dysfunction
McCullough, PA, ACC 2007
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Kaplan-Meier Estimates of the Probability of Death Through 6 Months: UA/NSTEMI
Morrow DA et al. J Am Coll Cardiol. 2003;41:1264-72.
Prob
abili
ty o
f Dea
th (%
)
Days since enrollment
BNP > 80 pg/mlBNP 80 pg/ml
6 months 8.4% vs. 1.8% p<0.001
0
5
10
0 50 100 150 180
BNP at baseline in 1,676 patients with non-ST-elevation ACS
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Probability of Death or Congestive Heart Failure Through 6 Months: UA/NSTEMI
0
5
10
15
20
0 30 60 90 120 150 180
Prob
abili
ty o
f Dea
th o
r CH
F (%
)
Days since enrollment
6 months 16.3% vs. 3.6% p<0.0001
Morrow DA et al. J Am Coll Cardiol. 2003;41:1264-72.
BNP > 80 pg/mlBNP 80 pg/ml
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Risk of CHF at 30 Days Stratified by BNP and cTnI: UA/NSTEMI
0.2
1.50.8
2.9
4.5
6.2
9
10.4
0
2
4
6
8
10
12
cTnI NEGP<0.0001
cTnI POSP<0.0001
cTnI NEGP<0.0001
cTnI POSP<0.0001
%
CHF Death/CHF
BNP >80 BNP <80
Morrow DA et al. J Am Coll Cardiol. 2003;41:1264-72.
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TACTICS-TIMI 18 Study Design
UA/NSTEMI
EarlyInvasive
EarlyConservative
PCI/ CABG
Cath/ PCI/ CABG
Medical Rx
Medical Rx
Endpoints
6 mos
Randomize-24 hrs
Chest pain
4- 48 108 hrs hrs
ASA, Hep,Tirofiban
Angio
Hour 0
ETT
+ischemia
BaselineBaselineTroponinTroponin
Cannon CP et al. Cannon CP et al. Am J CardiolAm J Cardiol 1998;82:731-6. 1998;82:731-6.
+ischemia+ischemia
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0 1 2 3 4 5 6Time (months)
0
4
8
12
16
20
% P
atien
ts
CONSINV
O.R 0.7895% CI (0.62, 0.97)p=0.025
19.4%
15.9%
Primary EndpointDeath, MI, Rehosp for ACS at 6 Months
Cannon CP, et al. N Engl J Med. 2001;344:1879-87.
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Troponin Substudy: 6 Month Results
00 0.5 0.5 1 1 1.5 1.5 2.0 2.0Invasive Better Conserv. Better
INV INV CONSCONS(%)(%) (%) (%)
16.916.9 14.514.510.110.1 23.023.015.715.7 24.624.6
4.34.3 5.35.35.95.9 13.313.39.09.0 12.012.0
11OO Composite Composite
< 0.01< 0.010.01 – 0.10.01 – 0.1> 0.1> 0.1
Death/MIDeath/MI
< 0.01< 0.010.01 – 0.10.01 – 0.1> 0.1> 0.1
P=0.01P=0.01
P<0.001P<0.001
P=0.06P=0.06
TnTTnT
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CONS CONS INVINV(%)(%) (%) (%) 19.419.4 15.315.319.619.6 17.017.0
17.817.8 14.914.921.721.7 17.117.1
27.727.7 20.120.116.416.4 14.214.2
26.326.3 16.416.415.315.3 15.615.6
19.419.4 15.915.9
11OO Endpoint Endpoint %Pts%Pts
MenMen (66%)(66%)WomenWomen (34%)(34%)
Age < 65 yrsAge < 65 yrs (57%)(57%)Age Age >> 65 yrs 65 yrs (43%)(43%)
DiabetesDiabetes (28%)(28%)No diabetesNo diabetes (72%)(72%)
ST ST * * (38%)(38%)No ST No ST (62%)(62%)
Total PopulationTotal Population
Death, MI, Rehosp ACS at 6 MonthsDeath, MI, Rehosp ACS at 6 Months
**Interaction P=0.006Interaction P=0.006 others P=NSothers P=NS
Subgroups: Primary Endpoint
INV Better CONS Better00 0.5 0.5 1 1 1.5 1.5
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Benefit of INV in TnT+ WomenEv
ent F
ree
Surv
ival
Even
t Fre
e Su
rviv
al
Time (days)Time (days)
1.00
0.70
0 50 !00 150 200
0.80
0.90Invasive
Conservative
OR=0.56
Log rank p=0.03
Glaser et alGlaser et alACC 2002ACC 2002
Death, MI, Rehosp for ACS
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ESC Guidelines for UA/NSTEMI
AspirinNitratesB-blockersHeparinClopidogrel
High-risk TroponinRec. Ischemia, DMHemodyn. InstabilityEarly Post MI angina
GP IIb/IIIa inhibitor
Coronary Angio
Low-RiskNormal Troponin on admissionand 12 h later
Stress TestBefore or After Discharge
Clinical suspicion ACSPE, ECG, Bloods
No ST elevation
Eur Heart J Sept 2000Bertrand, presented ESC 2002,
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UNSTABLE ANGINATIMI - 3B
CIRC. 1994, 89 : 1545-1556
1473 PATIENTS WITH REST ANGINA, ECG CHANGES OR NON Q INF.
1473 PATIENTS RANDOMISED TO TpaOR PLACEBO
SECOND RANDOMISATION TO EARLY CATH VS CONSERVATIVE CARE
NO DIFFERENCE IN DEATH OR MI
EARLIER DISCHARGE, FEWER ADMISSIONS AND NEED FOR ANTIANGINAL DRUGS IN INVASIVE STRATEGY
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TIMI- IIIB42 days (1 degree EP*) Invasive Conservative P value
N 740 733
Death(%) 2.4 2.5 NS
MI (%) 5.1 5.7 NS
D/MI/ +ETT (%) * 16.2 18.1 NS
LOS(days) 10.2 10.9 <0.001
Rehosp angina (%) 7.8 14.1 <0.001
>= 2 anginal meds (%) 44 52 0.02
D/MI/Rehosp (%) 15 22 0.007
# days rehosp 365 930 < 0.001
D/MI at 1 year (%) 10.8 12.2 NSAnderson HV et al.JACC 1995;26:1643-50
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The detrimental role of platelet derived soluble CD40L * in cardiovascular disease
InflammationInduces production/ release of pro inflammatory cytokines from vascular and atheroma cells
ThrombosisStabilizes platelet rich thrombi
RestenosisPrevents re-endothelialization of the injured vesselContributes to activation and proliferation of smooth muscle cells
*sCD40L= Soluble CD40L
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)Death or nonfatal myocardial infarction during six months of follow up
According to base line level of soluble CD40 ligand in placebo group (544 patients) and the Abcximab group (544 patients
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GP II b/IIIa in ACS: Intention to treat analysisDeath or MI at 30 days
The PRISM-Plus investigators. Nejm 1998; 338:1488-87
The PURSUIT Investigators. NEJM 1998; 339:436-43
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PRISM: Death/MI at 30 days
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FRISC II: 1 year death or MI
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One year outcomes TAXUS in ACS
TAXUS(n= 237) Control (n=213)
P value
Cardiac death 2.5 2.0 0.63
MI 3.8 6.2 0.27
CABG 1.7 6.1 0.05
PCI 5.2 13.0 0.0049
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In-Hospital Death or Recurrent Myocardial In-Hospital Death or Recurrent Myocardial Infarction Infarction
(GRACE + EUR. HEART SURVEY)(GRACE + EUR. HEART SURVEY)
Eur. H.J. 2002, 23, 1179Eur. H.J. 2002, 23, 1179Eur. H.J. 2002, 23, 1190Eur. H.J. 2002, 23, 1190
1.71.7--11.811.8- - Undetermined Undetermined ECGECG
------33UAUA
1.41.4222.42.466NSTEMINSTEMI
2.72.7337777STEMISTEMI
EHS-ACSEHS-ACS(%)(%)
GRACEGRACE(%)(%)
EHS-ACSEHS-ACS(%)(%)
GRACE GRACE (%)(%)
Type of DiseaseType of Disease
In-Hospital DeathIn-Hospital Death ReinfarctionReinfarction
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Outcomes of Percutaneous Intervention in Five TrialsOutcomes of Percutaneous Intervention in Five Trials
18/1418/1422/1222/1235/3035/3022/1622/1638/2338/23CABG at FUCABG at FU
61/4061/4036/1636/1652/1352/1342/2942/2944/2144/21PCI at FUPCI at FU
79/5479/5457/2857/2873/3973/3961/4461/4478/4378/43At end FUAt end FU
Invasive / selective Invasive / selective revascularizationrevascularization
1212242466662424Mean follow up (mo)Mean follow up (mo)
23233939262639392222Previous MI (%)Previous MI (%)
14141313252528281212Diabetes (%)Diabetes (%)
62626262616166667070Men (%)Men (%)
62626363666662626565Mean age (year)Mean age (year)
ICTUS ICTUS (N = 1200)(N = 1200)(604/596)(604/596)
RITA – 3RITA – 3(N = 1810)(N = 1810)(895/915)(895/915)
VINOVINO(N = 1131)(N = 1131)(64 / 67)(64 / 67)
TACTICSTACTICS(N = 2220)(N = 2220)
(1114/1106)(1114/1106)
FRISC IIFRISC II(N = 2457)(N = 2457)
(1222/1235)(1222/1235)
CharacteristicCharacteristic
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TACTICS – TIMI - 18
Treat Angina with Aggrastat and Determine Cost of Therapy with an Invasive or Conservative Strategy
New Engl. J. Med, June 2001, 344, 25 1879ACS patients : Randomised1114 Invasive Strategy1106 Conservative Strategy Similar demographic featuresStandard treatment with ASP, Hep, BB & Tirofiban 48 to 108 hours
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Results of the ISAR-REACT 2 Trial, Comparing Abciximab with Placebo
8.9
13.1
4.6
11.9
18.3
4.6
0
10
20
Abciximab Placebo
All Patients
(N = 2022)
High-riskTroponin +(N = 1049)
Low-riskTroponin -(N = 1049)
P = .03
P = .98
P = .02
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ACS Incidence of Early (in-hospital)
Revascularization in Several TrialsRevascularization in Several Trials71
60
73
44
76
9
36 39
10
40
0
10
20
30
40
50
60
70
80
FRISC-II TACTICS VINO RITA-3 ICTUS
Early Invasive Conservative
%
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ACS Incidence of Mortality or Nonfatal MI at the end
follow-up in several trials
10.4
7.36.3
7.6
1514.1
9.5
22.4
8.310
0
5
10
15
20
25
FRISC-II TACTICS VINO RITA-3 ICTUS
Early Invasive Conservative
%
FU (months) 12 6 6 12 12
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FRISC – IICONCLUSIONS
After one year in 100 patients invasive strategy :1) Saves 1.7 lives 2) Prevents 2 non fatal MI 3) Prevents 20 readmissions 4) Better symptoms relief 5) Lower cost 6) Preferred strategy for ischaemia with ECG
changes and raised serum enzymes
FRISC – IICONCLUSIONS
After one year in 100 patients invasive strategy :1) Saves 1.7 lives 2) Prevents 2 non fatal MI 3) Prevents 20 readmissions 4) Better symptoms relief 5) Lower cost 6) Preferred strategy for ischaemia with ECG
changes and raised serum enzymes
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Prognostic value of recurrent ischemia in ACS
Armstrong PW et al. Circulation 1998:98:1860-1868
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High TIMI score is associated with coronary thrombus in ACS
Sub analysis of PRISM-PLUS (n=1491)
D.A Morrow et al, AHA 2001
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Timing of Intervention in Patients with NSTEMI Acute Coronary Syndrome in
the CRUSADE Registry
.86.866.66.66.66.6Death / MI (%)Death / MI (%)
.36.363.03.02.92.9Recurrent MI (%)Recurrent MI (%)
.23.234.14.14.44.4Death (%)Death (%)P ValueP Value
23.4 Hours23.4 Hours(n = 45,548)(n = 45,548)
46.3 Hours 46.3 Hours (n = 10,804)(n = 10,804)
In-Hospital EventsIn-Hospital EventsTiming of Catheterization Timing of Catheterization
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Outcomes of the CRUSADE Trial : In-Hospital Death or Myocardial Infarction
4.74.78.98.9Death or MI (%)Death or MI (%)
3.13.13.73.7Post-admission MI (%)Post-admission MI (%)
2.02.06.26.2Mortality (%)Mortality (%)
Early Invasive Management Early Invasive Management (n = 9889)(n = 9889)
No Early Invasive No Early Invasive Management (n = 9889)Management (n = 9889)
OutcomeOutcome
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Troponin I Levels Predict the Riskof Mortality in ACS
Mor
talit
y at
42
Day
s
Antman EM et al. N Engl J Med. 1996;335:1342-9.
0 - <0.4 0.4 - <1.0 1.0 - <2.0 2.0 - <5.0 5.0 - < 9.0 9.0
831 174 148 134 50 67
Cardiac Troponin I (ng/ml)
1.0%
1.7%
3.4%3.7%
6.0%
7.5%
0
0.01
0.02
0.03
0.04
0.05
0.06
0.07
0.08
9.0
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Minor Troponin Elevations and Mortality• 34,227 patients admitted from ED
over a 3 yr. period who had at least 1 TnI sampled (48% of all pts admitted)
• Pts classified based on degree of elevation
– 0 not detected
– Negative 0–0.08 (99%)
– Indeterminant 0.09-0.2 (10% CV)
– Positive > 0.21
• Significant increase in mortality with increasing TnI
• Results same if analyzed
– Patients with ACS
– Patient who had serial sampling
Waxman DA. JACC. 2006;48:1755-62.
In-hospital Mortality, %
1.8
3.3
5
9.4
0
2.5
5
7.5
10
0 Neg Indeterm Pos
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Cardiac Troponin
Not an early marker
Currently there is no standardization across
Troponin I assays from different manufacturers
Diagnostic accuracy at the low end is variable
Sporadic elevations from non-atherothrombotic myocardial
damage may confuse interpretation
A low level troponin is not benign!
Limitations
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FRISC – IIFRAGMIN AND FAST REVASCULARISATION DURING INSTABILITY
IN CORONARY ARTERY DISEASE TRIAL (FRISC-II)LANCET 2000 : 356:9-16
Object :Compare Invasive And Non Invasive Strategy For Coronary Intervention In Patients With Unstable Coronary Artery Disease
Design :Prospective Randomised Multicentre Trial WithParallel Groups (58 Scandinavian Centres)
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FRISC – IIFRISC – IIInclusion criteria
Symptoms of ischaemiaSymptoms of ischaemia ECG changes > 0.1 mV DEP OR T WAVE ECG changes > 0.1 mV DEP OR T WAVE Inversion Or Inversion Or CPKMB > 6 CPKMB > 6 g/lg/l Troponin T > 0.1 Troponin T > 0.1 g/lg/l More than 3000 patients randomisedMore than 3000 patients randomised 1 year data available in 1222 invasive1 year data available in 1222 invasive And 1234 non invasive groupAnd 1234 non invasive group
FRISC – IIFRISC – IIInclusion criteria
Symptoms of ischaemiaSymptoms of ischaemia ECG changes > 0.1 mV DEP OR T WAVE ECG changes > 0.1 mV DEP OR T WAVE Inversion Or Inversion Or CPKMB > 6 CPKMB > 6 g/lg/l Troponin T > 0.1 Troponin T > 0.1 g/lg/l More than 3000 patients randomisedMore than 3000 patients randomised 1 year data available in 1222 invasive1 year data available in 1222 invasive And 1234 non invasive groupAnd 1234 non invasive group
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Multimarker Data and All-Cause Mortality
1.0
6.6
3.7
13.7
6.8
20.0
12.7
25.0
0
5
10
15
20
25M
orta
lity
0 1 2 3
Number or Markers Positive
30 Day1-Year
Kontos MC, Garg R, Anderson FP, Roberts CS, Tatum JL, Ornato JP, Jesse RL. A multimarker strategy predicts short- and long-term mortality n patients admitted for the exclusion of myocardial infarction. J Am Coll Cardiol 2005;45(3):217A.
P < 0.05 for all pairwise comparisonsN= 34613461
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FRISC – IICONCLUSIONS
After one year in 100 patients invasive strategy :1) Saves 1.7 lives 2) Prevents 2 non fatal MI 3) Prevents 20 readmissions 4) Better symptoms relief 5) Lower cost 6) Preferred strategy for ischaemia with ECG
changes and raised serum enzymes
FRISC – IICONCLUSIONS
After one year in 100 patients invasive strategy :1) Saves 1.7 lives 2) Prevents 2 non fatal MI 3) Prevents 20 readmissions 4) Better symptoms relief 5) Lower cost 6) Preferred strategy for ischaemia with ECG
changes and raised serum enzymes
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TROPONIN T LEVELS IN ACS & CARDIAC DEATH
1506 Patients
FRISC – Circ. 1996, 93 : 1651FRISC – Circ. 1996, 93 : 1651
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Antman RM et al JAMA 2000, 284, 835Antman RM et al JAMA 2000, 284, 835
% Population 4.3 17.3 32.0 29.3 13.0 3.4
6-7
SABATINE AND ANTMAN TIMI RISK SCORE FOR UA/NSTEMISABATINE AND ANTMAN TIMI RISK SCORE FOR UA/NSTEMI
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Annual Admissions for Acute Coronary Syndrome (ACS)
1.4 MillionNon-ST-Segment
Elevation ACS
600,000ST-Segment Elevation MI
~ 2.0 MM Patients Admittedto CCU or Telemetry Annually
Antman EM, et al. Circulation. 2004;110:588-636.Braunwald E, et al. Circulation. 2000;102:1193-1209.Antman EM, et al. Circulation. 2004;110:588-636.Braunwald E, et al. Circulation. 2000;102:1193-1209.
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Conclusion
In NSTE-ACS population,• TIMI risk score can be widely applied • At 30-day PURSUIT are better than others in
the high-risk group• GRACE is superior at long term follow-up in
high risk group
Heart 2012;98(S 2): E1–E319
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UNSTABLE ANGINA
• Ischemic discomfort • At rest or with minimal
exertion• Occurs in a crescendo
pattern or is severe • New onset with or no
ECG changes
NSTEMI• Ischemic discomfort • Rest or with minimal exertion• Occurs in a crescendo pattern
or is severe • New onset• With cardiac biomarkers of
necrosis creatine kinase-MB iso
enzyme [CK-MB] cardiac troponin)ECG changes
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830,000Myocardial Infarct (20%)
900,000Unstable Angina (23%)
910,000Non-Ischemic Cardiac (23%)
2,000,000 Non Cardiac
1,360,000 Non Cardiac (34%)
4,000,000 Suspected or Actual Cardiac
Chest Pain in theEmergency Department (ED)
100 million visits annually (US)~6 million chest pain visits
24,000 Missed ACS (1.2%)
Discharged Admitted
NCHS, Hospital Discharge Data, 2002 Pope et al, NEJM, 2000
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Acute ischaemic coronary syndromes Global Practice Pattern (OASIS) (1)
Source : Organisation to Assess Strategies For Ischaemic Syndromes Registry
(OASIS)8000 PatientsAcute Myocardial InfarctionNo ST ElevationPredischarge Coronary Angio :
Performed in Brazil 70 %, USA 60 %, Hungary 20 % Holland 7 %, Canada, Aust. Intermediate
PTCA, CABG : More Widespread Differences Between Countries
Circ. 1997, 96 (Suppl.) 1-40
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Prognostic value of baseline Troponins in ACSGUSTO-IIA: 30 Day mortality
Ohman EM et al. NEJM 1996;335:1331-4
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TIMI Risk Score Thrombolysis In Myocardial Infarction
Eur Heart J (May 2005) 26 (9):865-872.
Characteristics PointsHistorical
Age ≥65 yrs 1≥3 Risk factors for CAD 1
Known CAD (stenosis ≥50%) 1Aspirin use in past 7 days 1
PresentationRecent (≤24 h) severe angina 1
ST-segment deviation ≥0.5 mm 1↑Cardiac markers 1
Risk Score = Total Points (0–7)