1. Stanford ACS Guidelines 2003 David P. Lee, M.D. John S. Schroeder, M.D. *Donald Schreiber, M.D. Division of Cardiovascular Medicine and *Department of Emergency Medicine

2. Acute Coronary Syndromes Within the guidelines, ACS is defined as: –Unstable angina –Non-ST-elevation MI These guidelines do NOT apply to acute ST-elevation MI Stanford

3. Acute Coronary Syndromes –Based upon recent clinical data, these guidelines reflect new management strategies in ACS –Any questions or comments may be directed to any of the authors Stanford

4. HeparinEnoxaparin 0 5 10 15 20 25 30 35 40 02468101214 Months Cumulative event rate (%) Time to First Triple Endpoint (Death/MI/RA) ESSENCE Stanford

5. No. Pts 1 o Endpoint Death/MI Death MI Rehosp ACS 1114 15.9 7.3 3.3 4.8 11.0 1106 19.4 9.5 3.5 6.9 13.7 P valueINV (%)CONS (%) Cardiac Events at 6 Months 0.78 0.74 0.93 0.67 0.78 RR 0.025 <0.05 0.74 0.029 0.054 Stanford

6. 0123456 Time (months) 0 4 8 12 16 20 % Patients CONS INV RR 0.78 95% CI (0.62, 0.97) p=0.025 19.4% 15.9% Primary Endpoint Death, MI, Rehosp for ACS at 6 Months Stanford

7. Death/MI/ACS Rehosp (%) TIMI Risk Score CONS TIMI Risk Score: 6 month results % of Pts: 25% 60% 15% INV RR=0.75 CI (0.57, 1.00) RR=0.55 CI (0.33, 0.91) Stanford

8. Outcomes PlacClop %RRCIp # Patients63036259 1 st Co-Primary11.419.300.800.72-0.90< 0.001 CV Death5.475.080.930.79-1.08 MI6.655.180.770.67-0.89 Stroke1.381.200.860.63-1.18 Non CV death0.710.660.910.60-1.39 CURE Stanford

9. Cumulative Hazard Rates for CV Death/MI/Stroke P < 0.001 Clopidogrel Placebo Cumulative Hazard Rates Months of Follow-up 036912 6303 6259 5780 5866 4664 4779 3600 3644 2388 2418 Plac Clop N CURE Stanford

11. Acute Coronary Syndromes Data from several recent trials suggest: Unfractionated heparin should be replaced by low molecular weight heparin (enoxaparin) [ESSENCE] In higher-risk patients, early (“upstream”) use of a platelet glycoprotein IIb/IIIa receptor inhibitor should be strongly considered as well as early angiography (within 24 hours of hospitalization) [TACTICS/TIMI-18] Clopidogrel should be considered for early therapy [CURE/OASIS-4] An HMG-co-A-reductase inhibitor (statin) should be initiated during hospitalization [MIRACL] Stanford

12. TIMI Risk Score for UA / NSTEMI Age  65  3 CAD risk factors (FHx, HTN,  chol, DM, active smoker) ST deviation  0.5 mm  cardiac markers Recent (  24H) severe angina HISTORICAL PRESENTATION RISK SCORE = Total Points (0 - 7) Known CAD (stenosis  50%) ASA use in past 7 days 1 1 1 1 1 1 POINTS 0/1 2 3 4 5 6/7 RISK SCORE RISK OF CARDIAC EVENTS (%) BY 14 DAYS IN TIMI 11B* 3 5 7 12 19 DEATH OR MI DEATH, MI OR URGENT REVASC 5 8 13 20 26 41 *Entry criteria:UA or NSTEMI defined as ischemic pain at rest within past 24H, with evidence of CAD (ST segment deviation or +marker) Antman et al JAMA 2000; 284: 835 - 842 1 Stanford

13. ACS ALGORITHM in ED Chest pain Stanford Suspicious for cardiac? YesNo OPT f/u Low*High Risk ASA Clopidogrel +/- Enoxaparin ASA Clopidogrel Enoxaparin Tirofiban EARLY CATH (<24h) * = TIMI risk score> 2, active ECG changes, refractory pain, + marker Fxn test If +, CATH

14. Notes about the ACS algorithm 1.IV NTG and beta-blocker encouraged 2.OK to give enoxaparin before catheterization 3.If surgery is anticipated, hold clopidogrel 4.Early catheterization encouraged in higher-risk patients 5. If IIb/IIIa used on the floor, may use either tirofiban or eptifibatide Acute Coronary Syndromes Stanford

15. Notes about the ACS algorithm 7. If IIb/IIIa used, reduce enoxaparin dose to 0.75 mg/kg SQ BID 8.For patients with CrCl 2.0, give unfractionated heparin and adjust to ½ dose IIb/IIIa 9.No dosing adjustment necessary for obesity 10.Statin use should be started on day 1 Acute Coronary Syndromes Stanford

16. ASA325 mg chewable 81 mg if already on ACE-inhibitor Clopidogrel 300 mg po load, then 75 mg QD Enoxaparin1 mg/kg SQ BID 0.75 mg/kg SQ BID if IIb/IIIa used Tirofiban0.40 mcg/kg/min IV x 30 minutes, then 0.10 mcg/kg/min (*In Acute MI’s use 10mcg/kg IVB over 3 minutes, then 0.15mcg/kg/min*) Eptifibatide180 mcg IV bolus, then 2.0 mcg/kg/min Acute Coronary Syndromes Dosing Stanford