Risk stratification in UA and NSTEMI: Why and How?

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

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

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.

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

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?

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

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.

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.

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.

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.

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.

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.

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.

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.

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

Prognostic value of recurrent ischemia in ACS

Armstrong PW et al. Circulation 1998:98:1860-1868

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

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)

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

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.

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.

High TIMI score is associated with coronary thrombus in ACS

Subanalysis of PRISM-PLUS (n=1491)

D.A Morrow et al, AHA

2001

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.

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.

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

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

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

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


30-day and 1-year endpoint rates for PURSUIT score

Eur Heart J (May 2005) 26 (9):865-872.

30-day and 1-year endpoint rates for the TIMI score.

Eur Heart J (May 2005) 26 (9):865-872.

30-day and 1-year endpoint rates for the GRACE score.

Eur Heart J (May 2005) 26 (9):865-872.

Through 30 days in the heparin alone and tirofiban plus heparin treatment groups in (PRISM-PLUS), with

patients stratified by (TIMI) trial risk score


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


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

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

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)

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

Kaplan-Meier Estimates of the Probability of Death Through 6 Months: UA/NSTEMI


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

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


BNP > 80 pg/mlBNP 80 pg/ml

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


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

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.

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

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

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

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,

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

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

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

)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

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

PRISM: Death/MI at 30 days

FRISC II: 1 year death or MI

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

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

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

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

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

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

%

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

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




Prognostic value of recurrent ischemia in ACS

Armstrong PW et al. Circulation 1998:98:1860-1868

High TIMI score is associated with coronary thrombus in ACS

Sub analysis of PRISM-PLUS (n=1491)

D.A Morrow et al, AHA 2001

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

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

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

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

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

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)

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

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

TROPONIN T LEVELS IN ACS & CARDIAC DEATH

1506 Patients

FRISC – Circ. 1996, 93 : 1651FRISC – Circ. 1996, 93 : 1651

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

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.

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

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

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

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

Prognostic value of baseline Troponins in ACSGUSTO-IIA: 30 Day mortality

Ohman EM et al. NEJM 1996;335:1331-4

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)

Risk stratification in UA and NSTEMI: Why and How?

Health & Medicine

Transcript of Risk stratification in UA and NSTEMI: Why and How?