1. The Leeds Teaching Hospitals NHS Trust PHARMACOLOGY IN ACS OVERVIEW OF THE DATA : PRACTICAL ADVICE JIM McLENACHAN, LEEDS. 25 th January, 2007

2. The Leeds Teaching Hospitals NHS Trust CONFLICT OF INTEREST : ADVISORY BOARD MEMBER FOR LILLY AND NYCOMED

3. The Leeds Teaching Hospitals NHS Trust Pharmacology in ACS Anti-platelet agents Anti-thrombin agents Aspirin Clopidogrel Heparin (UFH, LMWH) ?IIb/IIIa antagonists ?Bivalirudin A and E / ward Cath lab ?Heparin ?Bivalirudin

4. The Leeds Teaching Hospitals NHS Trust Pharmacology in ACS Aspirin UFH LMWH IIb/IIIa antagonists Clopidogrel Bivalirudin 1995 1996 1999 2004

5. The Leeds Teaching Hospitals NHS Trust ADJUNCTIVE THERAPY IN PCI 45 year old male with chest pain ECG – T inversion V1 –V6 Troponin raised Angiogram - 95% LAD stenosis PCI to LAD

6. The Leeds Teaching Hospitals NHS Trust ADJUNCTIVE THERAPY IN PCI 45 year old male with chest pain ECG – T inversion V1 –V6 Troponin raised Angiogram - 95% LAD stenosis PCI to LAD Aspirin Clopidogrel LMWH ?IIb/IIIa inhibitor UFH ?IIb/IIIa inhibitor

7. The Leeds Teaching Hospitals NHS Trust ADJUNCTIVE THERAPY IN PCI 45 year old male with chest pain ECG – T inversion V1 –V6 Troponin raised Angiogram - 95% LAD stenosis PCI to LAD Aspirin Clopidogrel LMWH ?IIb/IIIa inhibitor UFH IIb/IIIa inhibitor 10am 14/1/07 11am 14/1/07 2pm 14/1/07 2.30pm 14/1/07

8. The Leeds Teaching Hospitals NHS Trust ADJUNCTIVE THERAPY IN PCI 45 year old male with chest pain ECG – T inversion V1 –V6 Troponin raised Angiogram - 95% LAD stenosis PCI to LAD Aspirin Clopidogrel LMWH ?IIb/IIIa inhibitor UFH ?IIb/IIIa inhibitor 10am 14/1/07 10am 15/1/07 2pm 18/1/07 2.30pm 18/1/07

9. The Leeds Teaching Hospitals NHS Trust ACUITY STUDY DESIGN 13,819 ACS patients13,819 ACS patients 3 antithrombotic regimens3 antithrombotic regimens - heparin + IIb/IIIa inhibitor - bivalirudin + IIb/IIIa inhibitor - bivalirudin alone Composite endpoint - death/MI/unplanned revasc. - major bleedingComposite endpoint - death/MI/unplanned revasc. - major bleeding NEJM 2006;355:2203-16

10. The Leeds Teaching Hospitals NHS Trust ACUITY STUDY RESULTS HEPARIN + IIb/IIIa INHIBITOR BIVALIRUDIN + IIB/IIIA INHIBITOR COMPOSITEISCHAEMIA 7.3% 7.3% 7.7% 7.7% MAJORBLEEDING 5.7% 5.7% 5.3% 5.3% NET CLINICAL OUTCOME 11.7% 11.7% 11.8% 11.8% NEJM 2006:355:2203-16

11. The Leeds Teaching Hospitals NHS Trust ACUITY But, “ Angiography was performed in 99% of patients at a median of 19.6 hours after admission……”

12. The Leeds Teaching Hospitals NHS Trust ISAR REACT 2 Design 2022 ACS patients2022 ACS patients Pretreated with clopidogrel 600 mgPretreated with clopidogrel 600 mg Randomised to abciximab or placeboRandomised to abciximab or placebo Primary composite of death / MI / urgent TVRPrimary composite of death / MI / urgent TVR JAMA 2006;295:1531-1538

13. The Leeds Teaching Hospitals NHS Trust ISAR REACT 2 Death / MI / urgent TVR at 30 days abciximab abciximab placebo placebo No troponin elevation 4.6% 4.6% Troponin elevation 13.1% 13.1% 18.3% ** 18.3% ** JAMA 2006;295:1531-1538

14. The Leeds Teaching Hospitals NHS Trust “….recommended strategy was an early PCI with stenting within 6 hours from establishment of the diagnosis of ACS”

15. The Leeds Teaching Hospitals NHS Trust ADJUNCTIVE THERAPY IN PCI 45 year old male with chest pain ECG – T inversion V1 –V6 Troponin raised Angiogram - 95% LAD stenosis PCI to LAD Aspirin Clopidogrel LMWH ?IIb/IIIa inhibitor UFH ?IIb/IIIa inhibitor 10am 14/1/07 10am 15/1/07 2pm 18/1/07 2.30pm 18/1/07

16. The Leeds Teaching Hospitals NHS Trust SUMMARY STEMI - aspirin, clopidogrel, abciximabSTEMI - aspirin, clopidogrel, abciximab NSTEMI - aspirin, clopidogrel, heparin for all - add IIb/IIIa inhibitor if early PCI - IIb/IIIa inhibitor for high risk PCI - bivalirudin plus IIb/IIIa inhibitor is a possible alternative strategyNSTEMI - aspirin, clopidogrel, heparin for all - add IIb/IIIa inhibitor if early PCI - IIb/IIIa inhibitor for high risk PCI - bivalirudin plus IIb/IIIa inhibitor is a possible alternative strategy

17. The Leeds Teaching Hospitals NHS Trust MY CONFLICTS OF INTEREST ARE: Dr McLenachan is Clinical Director of Cardiology at Leeds General Infirmary and is keen to save money by minimising the use of expensive drugs.