1. British Cardiac Intervention Society Risk Assessment In Acute Coronary Syndromes Dr David Newby BHF Senior Lecturer in Cardiology Associate Director of Wellcome Trust Clinical Research Facility

2. Case 1 46 year old woman Family history of ischaemic heart disease, hypertension, smoker and hypercholesterolaemia No prior history of angina 3 episodes of chest pain 12 hours prior to admission Already taking aspirin and statin on admission ECG normal Troponin I 1.2 µg/L

3. Case 1 Commenced on medical therapy and settles Would you manage the patient with: (a). In-patient coronary angiography and revascularise (b). Conservative treatment and consider angiography/revascularisation if symptoms recur

4. Case 2 79 year old man Non-smoker, hypertension and no risk factors Chronic stable angina for 15 years with known single vessel disease (angiogram 10 years ago) One episode of rest pain prior to admission Not taking aspirin ECG - minor ST depression on admission Troponin I <0.1 µg/L

5. Case 2 Commenced on medical therapy and settles Would you manage the patient with: (a). In-patient coronary angiography and revascularise (b). Conservative treatment and consider angiography/revascularisation if symptoms recur

6. TIMI Risk Score Age ≥ 65 years ≥3 Risk factors for coronary artery disease Significant coronary stenosis ST Segment deviation Severe anginal symptoms (≥2 anginal events in last 24 hours) Prior aspirin use (within last 7 days) Elevated serum cardiac markers Antman et al. JAMA 2000;284:835-842

8. TIMI Risk Score and Benefit with LMW Heparin

9. Case 1Case 2 Age ≥6501 ≥3 Risk factors for CAD10 Significant CAD01 ST Segment deviation01 Angina ≥2 times within 24 hrs10 Prior aspirin use10 Elevated cardiac markers10 Total TIMI Score43 14 Day Event Rate20%13% TIMI Risk Score

10. Other Risk Factors and Scores

11. Robust data on in-hospital & 6-month outcomes in over 12,000 patients in 14 different countries In well-characterized patients with ACS: –In-hospital to 6 month rates of: –death: ST-MI 12%, Non-ST-MI 13%, UA 8% –Stroke: 1.5 to 3% –Recurrent hospitalization for cardiac event: 17 to 20% Unselected patients reveal substantially higher event rates than those entered into recent trials A major challenge exists in the application of proven therapies to the full spectrum of patients with ACS GRACE Registry

12. SBP (per 20 mmHg increase) 0.70.69-0.78 Initial serum creatinine 1.21.15-1.35 Heart rate 30bpm 1.31.16-1.48 Initial cardiac enzyme + 1.61.32-2.00 Age (per 10 yr) 1.71.55-1.85 Killip class 2.01.81-2.29 ST deviation 2.41.90-3.00 Pre-hosp arrest 4.3 2.80-6.72 -2 –1 0 1 2 3 4 5 6 7 8 Multivariable Risk Model

13. Comparison of TIMI Risk Scores for Death: Antman Data Vs. GRACE Data 0 1 2 3 4 5 6 7 0/12345'6/7 TIMI Risk Score Antman GRACE Death Rate (%)

14. Outcome of “low-risk” patients with ACS Presentation with UA in the absence of dynamic ECG changes, no troponin elevation, no arrhythmia nor hypotension 6 month outcome: –16.6% readmission –8.7% revascularised –2.2% deaths –0.2% MI “Low-risk” is not no risk

15. FRISC II Study Wallentin et al. Lancet 2000;356:9-16.

16. RITA-3 Study Fox et al. Lancet 2002;360:743-751

17. Meta-analysis of Intervention Trials

18. Who Should We Target For Invasive Intervention?

19. MEN ≥65 YEARS CHRONIC ANGINA NON-SMOKERS CHEST PAIN at REST (TROPONIN +VE) ST DEPRESSION FRISC II et al. Lancet 1999;354:708-715

20. Case 1Case 2 Age1.000.66 Sex1.260.64 Smoking1.340.66 Angina > 3 months0.950.59 ST Segment deviation0.940.66 Elevated cardiac markers0.730.80 14 Day TIMI Event Rate20%13% Benefit from InterventionNoYes 6 Month Risk Reduction Based on FRISC Dataset

22. Risk Assessment In Acute Coronary Syndromes Evaluation of Treatment Benefit In Acute Coronary Syndromes

23. Single Vessel Disease Two Vessel Disease Three Vessel Disease 75% Left Main Stem 95% Left Main Stem 0.00.51.01.52.02.5 Harzard Ratio Survival Benefits of Revascularisation

24. 25 20 15 10 5 0 05-4950-85>85 Severity of Luminal Stenosis (%) Frequency (%) of 5 year Vessel Occlusion or Myocardial Infarction <50% 50-70% >70% 68% 18% 14% Severity of Underlying Luminal Stenosis in Patients with an Acute Myocardial Infarction Luminal Stenosis Frequency Degree of Stenosis in the Culprit Lesion of Acute Myocardial Infarction

25. Conclusions Risk scores need to be carefully applied Risk scores may be population dependent and not reflect ‘true life’ populations Low risk is not no risk High risk does not equate to most benefit from intervention Is the benefit of interventional strategies for acute coronary syndromes derived from revascularising patients with prior stable angina and prognostically significant disease?