Risk stratification in UA and NSTEMI: Why and How?

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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 rupture 1 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 plaque 1 This current understanding of how atherosclerosis progresses emphasizes the key role that acute and chronic antithrombotic therapy plays in all patients with unstable coronary syndromes 1 Reference 1. Cannon CP. J Thromb Thrombolysis 1995; 2: 205  218.
  • Efficacy and Safety of Subcutaneous Enoxaparin in Non–Q-wave Coronary Events (ESSENCE)
  • Platelet Receptor inhibition for Ischemic Syndrome Management in Patients Limited to very Unstable Signs and Symptoms (PRISM-PLUS
  • Treat angina with Aggrastat and determine Cost of Therapy with an Invasive or Conservative Strategy-Thrombolysis In Myocardial Infarction
  • This slide represents a diagnostic paradigm for patients presenting with ACS. Patients complaining of chest pain are first evaluated for the presence of ECG changes in the emergency department to determine if the pain is caused by coronary disease. The final diagnosis of a specific ACS incorporates both the ECG findings and results of assays for cardiac markers, such as CK-MB and troponins. By evaluating ECG results and identifying cardiac markers, a patient’s overall risk may be assessed and the level of aggressiveness for therapy can be determined. Patients with persistent ST-segment elevation demonstrated on an ECG are diagnosed as having STEMI, regardless of whether their cardiac markers are elevated. In the larger group of patients who have ischemic ECG changes other than persistent ST-segment elevation (eg, ST-segment depression, transient ST-segment elevation, T-wave inversions), measurement of cardiac markers is essential for distinguishing those who have UA (no elevation of cardiac markers) and those with NSTEMI (elevated cardiac markers).
  • The baseline characteristics of the population were well matched between the three treatment groups. Mean age was 60, 25% were female, 56% of patients had an MI at presentation and 9% presented with signs of congestive heart failure defined by Killip class. One quarter had the onset of ACS within 24 hours
  • The baseline characteristics of the population were well matched between the three treatment groups. Mean age was 60, 25% were female, 56% of patients had an MI at presentation and 9% presented with signs of congestive heart failure defined by Killip class. One quarter had the onset of ACS within 24 hours
  • Each year, there are 2 million patients admitted to hospitals in the US with ACS who present in 2 broad categories: ST-segment elevation MI (STEMI) and non-ST-segment elevation (NSTE) ACS. Approximately 600,000 patients per year exhibit ECG changes consistent with STEMI and another 1.4 million patients show ECG changes reflecting NSTEMI or unstable angina (UA).
  • Chest pain is the second most common reason for emergency department presentation (abdominal pain is #1) This is the breakdown of patient categories by discharge diagnosis Of the 2,000,000 discharged rapidly, about 24,000 are missed ACS, and many of these people go on to die. It is the number 1 reason for medical malpractice dollars lost by ED physicians in the USA. Of the 4,000,000 who are admitted, about 1.4M are non-cardiac chest pain 910,000 are non-ischemic cardiac causes (eg: congestive heart failure, arrhythmias) 900,000 are cardiac ischemia (stable and unstable angina) And 830,000 are AMI.
  • Risk stratification in UA and NSTEMI: Why and How?

    1. 1. RISK STRATIFICATION IN UAAND NSTEMI :WHY AND HOW? -Dr.DEV PAHLAJANI MD,FACC,FSCAI HOD INTERVENTIONAL CARDIOLOGY BREACH CANDY HOSPITAL, CONS.CARDIOLOGIST B.NANAVATI HOPSITAL MUMBAI
    2. 2. ACS is an Important Manifestation of Atherothrombosis1 Plaque rupture Stable UA Non- Q-waveOld term angina Q-wave MI MINew term Atherothrombosis UA/NSTEMI STEMI Days– Minutes– weeks hours Antithrombotic Thrombolysis therapy primary PCI UA=unstable angina; NSTEMI=non-ST-segment elevation myocardial infarction; PCI=percutaneous coronary intervention 1. Cannon CP. J Thromb Thrombolysis 1995; 2: 205–218.
    3. 3. 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: 205−218.
    4. 4. 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 MICoronaryocclusion & shortterm death Least Greatest
    5. 5. 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?
    6. 6. 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 factors Intermediate risk = 4-3 risk factors Antman EM et al: JAMA High risk = 5-7 risk factors 2000;284:835-42
    7. 7. 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 2Signs of heart failure 2ST-depression on presenting ECG 1 Eur Heart J (May 2005) 26 (9):865-872.
    8. 8. GRACE(0–258) Age (years) Heart rate (bpm) Systolic BP (mmHg) <40 0 <70 0 <80 63  40–49 18  170–89 7  180–99 58  50–59 36  190–109 13  100–119 47  60–69 55  110–149 23  120–139 37  70–79 73  150–199 36  140–159 26  ≥80 91  >200 46  160–199 11 Creatinine (mg/dL)  >200 0 Killip class 0.0- 0.39 2 Cardiac arrest atClass I 0  0.4–0.79 5 admission 43Class II 21  0.8–1.19 8 Elevated cardiacClass III 43  1.2–1.59 11 markers 15Class IV 64  1.6–1.99 14 ST-segment  0.2–3.99 23 deviation 30  >4 31 Eur Heart J (May 2005) 26 (9):865-872.
    9. 9. TIMI, PURSUIT, and GRACE riskscores: sustained prognostic value and interaction with revascularization in NSTE‐ACS Pedro de Araújo Gonçalves, Jorge Ferreira, Carlos Aguiar and Ricardo Seabra-Gomes Eur Heart J (May 2005) 26 (9):865-872.
    10. 10. 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 .
    11. 11. 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.
    12. 12. 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.
    13. 13. Comparison of the predictive accuracy of the risk scores 30 days 1 year Δ 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 0.04GRACE vs. TIMI 0.121 0.054 0.130 0.004 Eur Heart J (May 2005) 26 (9):865-872.
    14. 14. ConclusionsRSs 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.
    15. 15. The TIMI unstable angina risk score7 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 factors Intermediate risk= 3-4 risk factors High risk = 5-7 risk factors Antman EM et al. JAMA 2000:284:835-42
    16. 16. Prognostic value of recurrent ischemia in ACS Armstrong PW et al. Circulation 1998:98:1860-1868
    17. 17. Troponin T and ST segment depression are independent predictors of adverse cardiac events at FU in ACS Univariate OR( 95% Cl) Multivariate OR (95% Cl)ST segment depression1 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 T0.01-0.047 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
    18. 18. TIMI Risk Score: 1oEP at 6 mos OR=0.55 CONS INV CI (0.33, 0.91) 35 OR=0.75 30.6Death/MI/ACS Rehosp (%) 30 CI (0.57, 1.00) 25 20.3 19.5 20 16.1 15 11.8 12.8 10 5 0 Low 0-2 Intermed. 3-4 High 5-7 TIMI Risk Score % of Pts: 25% 60% 15%
    19. 19. TACTICS TIMI 18 Troponin T : Primary endpoint Death / MI / rehospitalization for ACS at 6 months OR = 0.53 p<0.001 30 Conservative Invasive Interaction p<0.001 24.5Incidence (%) 25 P=NS 20 16.9 TnT cut point = 0.001 14.5 14.2 ng/ml (54 % of patients 15 were Troponin T 10 positive) 5 0 TnT negative TnT positive
    20. 20. TACTICS-TIMI 18: Invasive vs. Cons. Troponin T >0.01 ng/dl Primary Endpoint: Death/MI/Rehosp ACS TnT +, CONS 24.2% TnT -, INV 14.8% TnT +, INV TnT -, CONS Morrow DA, et al. JAMA 2001;286:2405-2412.
    21. 21. Through 14 days in the un fractionated heparin (UFH) andenoxaparin (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.
    22. 22. High TIMI score is associated with coronary thrombus in ACS Subanalysis of PRISM-PLUS (n=1491) D.A Morrow et al, AHA 2001
    23. 23. Evaluation of B-Type Natriuretic Peptide forRisk Assessment in Unstable Angina/Non-ST- Elevation Myocardial 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.
    24. 24. Mortality Risk Stratified by B-Type Natriuretic Peptide Levels Over Range of 40 to 160 pg/ml: UA/NSTEMI 14 12 6 Month Mortality (%) 10.9 11.1 10 8 7.1 6 3.6 4 1.7 1.9 2 0 BNP (pg/ml) >80- ≤ 40 >40- ≤80 >100- ≤120 >120- ≤160 >160 ≤100 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.
    25. 25. Combination of cTnI, CRP, BNP in ACS OPUS-TIMI 16 TACTICS-TIMI 18 6 14 N=163530-Day Mortality Relative Risk 30-Day Mortality Relative Risk N=450 Validation 5 12 P = 0.014 P < 0.0001 10 4 8 3 6 2 4 1 2 0 0 0 1 2 3 0 1 2 3 N= 67 150 155 78 N = 504 717 324 90 # of Elevated Cardiac Biomarkers # of Elevated Cardiac Biomarkers Sabatine MS et al. Circulation. 2002;105:1760-3.
    26. 26. 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
    27. 27. Multimarker Data N= 3461 80 72.0 70 60 Percent of Cases 50 40 30 20 16.0 10 6.8 5.9 0 0 1 2 3 Number or Markers PositiveKontos 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.
    28. 28. Risk of Death or MI at 30 Days Stratified by BNP and cTnI: UA/NSTEMI 10 Death Death/MI BNP >80 7.9 8 BNP <80 7.5 6.4 6 5.4 4.5 % 4 2 2 1.4 0.7 0 cTnI NEG cTnI POS cTnI NEG cTnI POS P=0.004 P<0.001 P=0.008 P=0.4 Morrow DA et al. J Am Coll Cardiol. 2003;41:1264-72.
    29. 29. 30-day and 1-year endpoint rates for PURSUIT score Eur Heart J (May 2005) 26 (9):865-872.
    30. 30. 30-day and 1-year endpoint rates for the TIMI score. Eur Heart J (May 2005) 26 (9):865-872.
    31. 31. 30-day and 1-year endpoint rates for the GRACE score. Eur Heart J (May 2005) 26 (9):865-872.
    32. 32. Through 30 days in the heparin alone and tirofibanplus heparin treatment groups in (PRISM-PLUS), with patients stratified by (TIMI) trial risk score J Am Coll Cardiol. 2003;41(4s1):S89-S95.
    33. 33. Through six months in the invasive (INV) andconservative (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.
    34. 34. Acute Evaluation of ACS Presentation Chest Pain or Short of Breath ST-Segment ST-Segment ECG Normal Depression ElevationBlood Marker Panel – + – + + Diagnosis Unstable Rule-Out Acute MI Angina Adapted from Braunwald E, et al. Available at: http://www.americanheart.org/downloadable/heart/1022188973899unstable_may8.pdf. Adapted from Antman EM, et al. Circulation.2004 Aug 31;110(9):e82-292.
    35. 35. Clinical Utilization of Cardiac Troponin and Natriuretic Peptides in ACS and CHFConsultant 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
    36. 36. Troponin i levels predict the risk of mortality Changes in Focus on Heart Failure in ua/nstemi 7.5 8 Mortality at 42 Days (% of patients) 6.0 6 3.7 4 3.4 1.7 2 1.0 831 174 148 134 50 67 0 0 to <0.4 0.4 to <1.0 1.0 to <2.0 2.0 to <5.0 5.0 to <9.0 >9.0 Cardiac Troponin I (ng/ml) Risk Ratio 1.0 1.8 3.5 3.9 6.2 7.8 Antman N Engl J Med. 335:1342, 1996
    37. 37. 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
    38. 38. Kaplan-Meier Estimates of theProbability of Death Through 6 Months: UA/NSTEMI BNP at baseline in 1,676 patients 10 BNP > 80 pg/ml with non-ST-elevation ACS BNP ≤ 80 pg/ml Probability of Death (%) 6 months 8.4% 5 vs. 1.8% p<0.001 0 0 50 100 150 180 Days since enrollment Morrow DA et al. J Am Coll Cardiol. 2003;41:1264-72.
    39. 39. Probability of Death or Congestive Heart Failure Through 6 Months: UA/NSTEMI 20 BNP > 80 pg/ml BNP ≤ 80 pg/mlProbability of Death or CHF (%) 15 10 6 months 16.3% vs. 3.6% p<0.0001 5 0 0 30 60 90 120 150 180 Days since enrollment Morrow DA et al. J Am Coll Cardiol. 2003;41:1264-72.
    40. 40. Risk of CHF at 30 Days Stratified by BNP and cTnI: UA/NSTEMI 12 CHF Death/CHF 10.4 10 BNP >80 9 BNP <80 8 6.2 6 % 4.5 4 2.9 2 1.5 0.8 0.2 0 cTnI NEG cTnI POS cTnI NEG cTnI POS P<0.0001 P<0.0001 P<0.0001 P<0.0001 Morrow DA et al. J Am Coll Cardiol. 2003;41:1264-72.
    41. 41. TACTICS-TIMI 18 Study Design PCI/ CABG Early Angio Invasive Medical RxUA/ ASA, Hep,NSTEMI Tirofiban Endpoints Baseline Early Medical Rx ETT Troponin Conservative +ischemia +ischemia +ischemia Chest Cath/ PCI/ CABG pain Randomize -24 Hour 4- 48 108 6 mos 0 hrs hrs hrs Cannon CP et al. Am J Cardiol 1998;82:731-6.
    42. 42. Primary Endpoint Death, MI, Rehosp for ACS at 6 Months 20 19.4% 16 15.9%% Patients 12 O.R 0.78 8 95% CI (0.62, 0.97) p=0.025 4 CONS 0 INV 0 1 2 3 4 5 6 Time (months) Cannon CP, et al. N Engl J Med. 2001;344:1879-87.
    43. 43. Troponin Substudy: 6 Month Results INV CONS1O Composite (%) (%)< 0.01 16.9 14.50.01 – 0.1 P=0.01 10.1 23.0> 0.1 P<0.001 15.7 24.6Death/MI< 0.01 4.3 5.30.01 – 0.1 P=0.06 5.9 13.3> 0.1 9.0 12.0 TnT 0 0.5 1 1.5 2.0 Invasive Better Conserv. Better
    44. 44. Subgroups: Primary Endpoint Death, MI, Rehosp ACS at 6 Months CONS INV1 Endpoint O %Pts (%) (%)Men (66%) 19.4 15.3Women (34%) 19.6 17.0Age < 65 yrs (57%) 17.8 14.9Age > 65 yrs (43%) 21.7 17.1Diabetes (28%) 27.7 20.1No diabetes (72%) 16.4 14.2ST ∆ * (38%) 26.3 16.4No ST ∆ (62%) 15.3 15.6 19.4 15.9Total Population*Interaction P=0.006 0 0.5 1 1.5others P=NS INV Better CONS Better
    45. 45. Benefit of INV in TnT+ Women Death, MI, Rehosp for ACS 1.00 OR=0.56 Invasive Log rank p=0.03 0.90Event Free Survival 0.80 Conservative 0.70 Glaser et al ACC 2002 0 50 !00 150 200 Time (days)
    46. 46. ESC Guidelines for UA/NSTEMIClinical suspicion ACSPE, ECG, Bloods No ST elevation High-risk ↑ Troponin GP IIb/IIIa inhibitor Rec. Ischemia, DM Aspirin Coronary Angio Hemodyn. Instability Nitrates Early Post MI angina B-blockers Heparin Low-Risk Stress Test Normal Troponin Before or Clopidogrel After on admission Discharge and 12 h later Bertrand, presented ESC 2002, Eur Heart J Sept 2000
    47. 47. UNSTABLE ANGINA TIMI - 3BCIRC. 1994, 89 : 1545-15561473 PATIENTS WITH REST ANGINA,ECG CHANGES OR NON Q INF.1473 PATIENTS RANDOMISED TO TpaOR PLACEBOSECOND RANDOMISATION TO EARLYCATH VS CONSERVATIVE CARENO DIFFERENCE IN DEATH OR MIEARLIER DISCHARGE, FEWER ADMISSIONSAND ↓ NEED FOR ANTIANGINAL DRUGSIN INVASIVE STRATEGY
    48. 48. TIMI- IIIB42 days (1 degree EP*) Invasive Conservative P valueN 740 733Death(%) 2.4 2.5 NSMI (%) 5.1 5.7 NSD/MI/ +ETT (%) * 16.2 18.1 NSLOS(days) 10.2 10.9 <0.001Rehosp angina (%) 7.8 14.1 <0.001>= 2 anginal meds (%) 44 52 0.02D/MI/Rehosp (%) 15 22 0.007# days rehosp 365 930 < 0.001D/MI at 1 year (%) 10.8 12.2 NS Anderson HV et al.JACC 1995;26:1643-50
    49. 49. The detrimental role of platelet derivedsoluble CD40L * in cardiovascular disease Inflammation Induces production/ release of pro inflammatory cytokines from vascular and atheroma cells Thrombosis Stabilizes platelet rich thrombi Restenosis Prevents re-endothelialization of the injured vessel*sCD40L= Soluble CD40L Contributes to activation and proliferation of smooth muscle cells
    50. 50. )Death or nonfatal myocardial infarction during six months of follow upAccording to base line level of soluble CD40 ligand in placebo group (544 patients) and the Abcximab group (544 patients
    51. 51. GP II b/IIIa in ACS: Intention to treat analysis Death or MI at 30 days The PRISM-Plus investigators. Nejm 1998; The PURSUIT Investigators. NEJM 338:1488-87 1998; 339:436-43
    52. 52. PRISM: Death/MI at 30 days
    53. 53. FRISC II: 1 year death or MI
    54. 54. One year outcomes TAXUS in ACS TAXUS(n= 237) Control P value (n=213)Cardiac death 2.5 2.0 0.63MI 3.8 6.2 0.27CABG 1.7 6.1 0.05PCI 5.2 13.0 0.0049
    55. 55. In-Hospital Death or Recurrent Myocardial Infarction (GRACE + EUR. HEART SURVEY) In-Hospital Death ReinfarctionType of Disease GRACE EHS-ACS GRACE EHS-ACS (%) (%) (%) (%)STEMI 7 7 3 2.7NSTEMI 6 2.4 2 1.4UA 3 - - -Undetermined - 11.8 - 1.7ECG Eur. H.J. 2002, 23, 1179 Eur. H.J. 2002, 23, 1190
    56. 56. Outcomes of Percutaneous Intervention in Five TrialsCharacteristic FRISC II TACTICS VINO RITA – 3 ICTUS (N = 2457) (N = 2220) (N = 1131) (N = 1810) (N = 1200) (1222/1235) (1114/1106) (64 / 67) (895/915) (604/596)Mean age (year) 65 62 66 63 62Men (%) 70 66 61 62 62Diabetes (%) 12 28 25 13 14Previous MI (%) 22 39 26 39 23Mean follow up (mo) 24 6 6 24 12Invasive / selectiverevascularizationAt end FU 78/43 61/44 73/39 57/28 79/54PCI at FU 44/21 42/29 52/13 36/16 61/40CABG at FU 38/23 22/16 35/30 22/12 18/14
    57. 57. TACTICS – TIMI - 18Treat Angina with Aggrastat and Determine Cost ofTherapy with an Invasive or Conservative Strategy New Engl. J. Med, June 2001, 344, 25 1879ACS patients : Randomised1114 Invasive Strategy1106 Conservative StrategySimilar demographic featuresStandard treatment with ASP, Hep, BB &Tirofiban 48 to 108 hours
    58. 58. Results of the ISAR-REACT 2 Trial, Comparing Abciximab with Placebo Abciximab Placebo P = .0220 18.3 P = .03 13.1 11.910 8.9 P = .98 4.6 4.60 All Patients High-risk Low-risk Troponin + Troponin - (N = 2022) (N = 1049) (N = 1049)
    59. 59. ACS Incidence of Early (in-hospital) Revascularization in Several Trials 80 76 71 73 70 60 60 50 44 39 40 40 36% 30 20 9 10 10 0 FRISC-II TACTICS VINO RITA-3 ICTUS Early Invasive Conservative
    60. 60. ACS Incidence of Mortality or Nonfatal MI at the end follow-up in several trials Early Invasive Conservative 25 22.4 20 15 15 14.1 % 10.4 9.5 10 10 7.3 7.6 8.3 6.3 5 0 FRISC-II TACTICS VINO RITA-3 ICTUSFU (months) 12 6 6 12 12
    61. 61. FRISC – II CONCLUSIONSAfter one year in 100 patients invasive strategy :1) Saves 1.7 lives2) Prevents 2 non fatal MI3) Prevents 20 readmissions4) Better symptoms relief5) Lower cost6) Preferred strategy for ischaemia with ECG changes and raised serum enzymes
    62. 62. Prognostic value of recurrent ischemia in ACS Armstrong PW et al. Circulation 1998:98:1860-1868
    63. 63. High TIMI score is associated with coronary thrombus in ACS Sub analysis of PRISM-PLUS (n=1491) D.A Morrow et al, AHA 2001
    64. 64. Timing of Intervention in Patients with NSTEMI Acute Coronary Syndrome in the CRUSADE Registry Timing of CatheterizationIn-Hospital Events 46.3 Hours 23.4 Hours (n = 10,804) (n = 45,548) P ValueDeath (%) 4.4 4.1 .23Recurrent MI (%) 2.9 3.0 .36Death / MI (%) 6.6 6.6 .86
    65. 65. Outcomes of the CRUSADE Trial :In-Hospital Death or Myocardial InfarctionOutcome No Early Invasive Early Invasive Management ( Management (n = 9889 ( (n = 9889Mortality (%) 6.2 2.0Post-admission MI (%) 3.7 3.1Death or MI (%) 8.9 4.7
    66. 66. Troponin I Levels Predict the Risk of Mortality in ACS 0.08 7.5% 0.07 6.0%Mortality at 42 Days 0.06 0.05 0.04 3.7% 3.4% 0.03 0.02 1.7% 1.0% 0.01 831 174 148 134 50 67 0 0 - <0.4 0.4 - <1.0 1.0 - <2.0 2.0 - <5.0 5.0 - < 9.0 ≥ 9.0 Cardiac Troponin I (ng/ml) Antman EM et al. N Engl J Med. 1996;335:1342-9.
    67. 67. 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 10 9.4 admitted) In-hospital Mortality, %• Pts classified based on degree of elevation 7.5 – 0 not detected – Negative 0–0.08 (99%) 5 5 – Indeterminant 0.09-0.2 (10% CV) 3.3 – Positive > 0.21• Significant increase in mortality 2.5 1.8 with increasing TnI• Results same if analyzed 0 – Patients with ACS 0 Neg Indeterm Pos – Patient who had serial sampling Waxman DA. JACC. 2006;48:1755-62.
    68. 68. Cardiac Troponin Limitations 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!
    69. 69. FRISC – II FRAGMIN AND FAST REVASCULARISATION DURING INSTABILITY IN CORONARY ARTERY DISEASE TRIAL (FRISC-II) LANCET 2000 : 356:9-16Object :Compare Invasive And Non Invasive Strategy ForCoronary Intervention In Patients With UnstableCoronary Artery Disease Design :Prospective Randomised Multicentre Trial WithParallel Groups (58 Scandinavian Centres)
    70. 70. FRISC – II Inclusion criteria Symptoms of ischaemia ECG changes > 0.1 mV DEP OR T WAVE Inversion Or CPKMB > 6 µ g/l Troponin T > 0.1 µ g/l More than 3000 patients randomised 1 year data available in 1222 invasive And 1234 non invasive group
    71. 71. Multimarker Data and All-Cause Mortality N= 3461 P < 0.05 for all pairwise comparisons 25 25.0 20 20.0 Mortality 15 13.7 12.7 10 30 Day 6.6 6.8 1-Year 5 3.7 1.0 0 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 mort n patients admitted for the exclusion of myocardial infarction. J Am Coll Cardiol 2005;45(3):217A.
    72. 72. FRISC – II CONCLUSIONSAfter one year in 100 patients invasive strategy :1) Saves 1.7 lives2) Prevents 2 non fatal MI3) Prevents 20 readmissions4) Better symptoms relief5) Lower cost6) Preferred strategy for ischaemia with ECG changes and raised serum enzymes
    73. 73. TROPONIN T LEVELSIN ACS & CARDIAC DEATH 1506 Patients FRISC – Circ. 1996, 93 : 1651
    74. 74. SABATINE AND ANTMAN TIMI RISK SCORE FOR UA/NSTEMI 6-7pulation 4.3 17.3 32.0 29.3 13.0 3.4 Antman RM et al JAMA 2000, 284, 835
    75. 75. Annual Admissions for Acute Coronary Syndrome (ACS) ~ 2.0 MM Patients Admitted to CCU or Telemetry Annually 600,000 1.4 MillionST-Segment Elevation MI Non-ST-Segment Elevation ACS Antman EM, et al. Circulation. 2004;110:588-636. Braunwald E, et al. Circulation. 2000;102:1193-1209.
    76. 76. ConclusionIn 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
    77. 77. UNSTABLE ANGINA NSTEMI• Ischemic discomfort • Ischemic discomfort• At rest or with minimal • Rest or with minimal exertion exertion• Occurs in a crescendo • Occurs in a crescendo pattern or is severe pattern or is severe• New onset with or no • New onset ECG changes • With cardiac biomarkers of necrosis  creatine kinase-MB iso enzyme [CK-MB]  cardiac troponin)
    78. 78. Chest Pain in the Emergency Department (ED) 100 million visits annually (US) ~6 million chest pain visitsDischarged Admitted2,000,000 Non 4,000,000Cardiac Suspected or Actual Cardiac24,000 1,360,000Missed ACS Non Cardiac(1.2%) (34%) 910,000 Non-Ischemic Cardiac (23%) 900,000 Unstable Angina (23%) 830,000 Myocardial Infarct (20%) NCHS, Hospital Discharge Data, 2002 Pope et al, NEJM, 2000
    79. 79. 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
    80. 80. Prognostic value of baseline Troponins in ACS GUSTO-IIA: 30 Day mortality Ohman EM et al. NEJM 1996;335:1331-4
    81. 81. TIMI Risk ScoreThrombolysis In Myocardial Infarction Characteristics Points Historical Age ≥65 yrs 1 ≥3 Risk factors for CAD 1 Known CAD (stenosis ≥50%) 1 Aspirin use in past 7 days 1 Presentation Recent (≤24 h) severe angina 1 ST-segment deviation ≥0.5 mm 1 ↑Cardiac markers 1 Risk Score = Total Points (0–7) Eur Heart J (May 2005) 26 (9):865-872.

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