The Leeds Teaching Hospitals
NHS Trust
PHARMACOLOGY IN ACS
OVERVIEW OF THE DATA : PRACTICAL ADVICE
JIM McLENACHAN, LEEDS. 25th January,
2007
The Leeds Teaching Hospitals
NHS Trust
CONFLICT OF INTEREST :
ADVISORY BOARD MEMBER FOR LILLY AND NYCOMED
The Leeds Teaching Hospitals
NHS Trust
Pharmacology in ACS
Anti-platelet agents A and E / ward Aspirin Clopidogrel
Anti-thrombin agents
Heparin (UFH, LMWH)
?IIb/IIIa antagonists
?Bivalirudin
Cath lab
?Heparin ?IIb/IIIa antagonists
?Bivalirudin
The Leeds Teaching Hospitals
NHS Trust
Pharmacology in ACS
Aspirin UFH 1995 1996 1999 2004 LMWH IIb/IIIa antagonists
Clopidogrel
Bivalirudin
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
The Leeds Teaching Hospitals
NHS Trust
ADJUNCTIVE THERAPY IN PCI
45 year old male with chest pain ECG – T inversion V1 –V6 Aspirin Clopidogrel LMWH ?IIb/IIIa inhibitor UFH
Troponin raised
Angiogram - 95% LAD stenosis
PCI to LAD
?IIb/IIIa inhibitor
The Leeds Teaching Hospitals
NHS Trust
ADJUNCTIVE THERAPY IN PCI
45 year old male with chest pain ECG – T inversion V1 –V6 Aspirin Clopidogrel LMWH ?IIb/IIIa inhibitor UFH 10am 14/1/07
Troponin raised
11am 14/1/07 2pm 14/1/07
Angiogram - 95% LAD stenosis
PCI to LAD
IIb/IIIa inhibitor
2.30pm 14/1/07
The Leeds Teaching Hospitals
NHS Trust
ADJUNCTIVE THERAPY IN PCI
45 year old male with chest pain ECG – T inversion V1 –V6 Aspirin Clopidogrel LMWH ?IIb/IIIa inhibitor UFH 10am 14/1/07
Troponin raised
10am 15/1/07 2pm 18/1/07
Angiogram - 95% LAD stenosis
PCI to LAD
?IIb/IIIa inhibitor
2.30pm 18/1/07
The Leeds Teaching Hospitals
NHS Trust
ACUITY STUDY DESIGN
• 13,819 ACS patients • 3 antithrombotic regimens - heparin + IIb/IIIa inhibitor - bivalirudin + IIb/IIIa inhibitor - bivalirudin alone • Composite endpoint - death/MI/unplanned revasc. - major bleeding
NEJM 2006;355:2203-16
The Leeds Teaching Hospitals
NHS Trust
ACUITY STUDY RESULTS
HEPARIN + IIb/IIIa INHIBITOR BIVALIRUDIN + IIB/IIIA INHIBITOR
COMPOSITE ISCHAEMIA MAJOR BLEEDING NET CLINICAL OUTCOME
7.3% 5.7% 11.7%
7.7% 5.3% 11.8%
NEJM 2006:355:2203-16
The Leeds Teaching Hospitals
NHS Trust
ACUITY
But,
“Angiography was performed in 99% of patients
at a median of 19.6 hours after admission……”
The Leeds Teaching Hospitals
NHS Trust
ISAR REACT 2 Design
• • • • 2022 ACS patients Pretreated with clopidogrel 600 mg Randomised to abciximab or placebo Primary composite of death / MI / urgent TVR
JAMA 2006;295:1531-1538
The Leeds Teaching Hospitals
NHS Trust
ISAR REACT 2 Death / MI / urgent TVR at 30 days
abciximab No troponin elevation Troponin elevation 4.6% 13.1%
placebo 4.6% 18.3% **
JAMA 2006;295:1531-1538
The Leeds Teaching Hospitals
NHS Trust
“….recommended strategy was an early PCI with stenting within 6 hours from establishment of the diagnosis of ACS”
The Leeds Teaching Hospitals
NHS Trust
ADJUNCTIVE THERAPY IN PCI
45 year old male with chest pain ECG – T inversion V1 –V6 Aspirin Clopidogrel LMWH ?IIb/IIIa inhibitor UFH 10am 14/1/07
Troponin raised
10am 15/1/07 2pm 18/1/07
Angiogram - 95% LAD stenosis
PCI to LAD
?IIb/IIIa inhibitor
2.30pm 18/1/07
The Leeds Teaching Hospitals
NHS Trust
SUMMARY
• STEMI - 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 strategy
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.