A ggrastat- Phase of the AGGRASTAT to ZOCOR (A to Z) Trial Comparison of the safety and efficacy of unfractionated heparin versus enoxaparin in combination with tirofiban and aspirin in individuals who present with non-ST elevation acute coronary syndromes Presented at ACC 2003 Late Breaking Clinical Trials

www. Clinical trial results.orgBackgroundBackground Enoxaparin (ENOX) has demonstrated superiority to unfractionated heparin (UFH) in ACS populations managed conservatively in the absence of GP IIb/IIIa inhibitors (TIMI 11, ESSENCE) GP IIb/IIIa inhibitors are now recommended for high risk ACS patients in whom an invasive strategy is planned Trials suggest additional benefit of a low molecular weight heparin (LMWH) over UFH when used in combination with GP IIb/IIIa inhibitors (INTERACT) The goal of the A Phase of A to Z was to compare the safety and efficacy of enoxaparin (ENOX) vs unfractionated heparin (UFH) in combination with tirofiban and aspirin in the management of NSTEMI-ACS Enoxaparin (ENOX) has demonstrated superiority to unfractionated heparin (UFH) in ACS populations managed conservatively in the absence of GP IIb/IIIa inhibitors (TIMI 11, ESSENCE) GP IIb/IIIa inhibitors are now recommended for high risk ACS patients in whom an invasive strategy is planned Trials suggest additional benefit of a low molecular weight heparin (LMWH) over UFH when used in combination with GP IIb/IIIa inhibitors (INTERACT) The goal of the A Phase of A to Z was to compare the safety and efficacy of enoxaparin (ENOX) vs unfractionated heparin (UFH) in combination with tirofiban and aspirin in the management of NSTEMI-ACS

www. Clinical trial results.org Non-inferiority = upper bound of one-sided 95% CI < Upper BoundOne-Sided 95% CI in A to Z: 1.05, Hazard ratio of 0.88, p=NS Non-inferiority criteria met Non-inferiority = upper bound of one-sided 95% CI < Upper BoundOne-Sided 95% CI in A to Z: 1.05, Hazard ratio of 0.88, p=NS Non-inferiority criteria met 7 Day Primary Endpoint Composite of Death, MI and Refractory Ischemia Incidence (%) Presented at ACC 2003 Late Breaking Clinical Trials

www. Clinical trial results.orgConclusions:Conclusions: A to Z met its primary hypothesis: Among pts with NSTEMI ACS treated with tirofiban and ASA, Enoxaparin is non-inferior to UFH for the composite of Death, MI and Refractory Ischemia Based on the data from TIMI 11, ESSENCE, INTERACT and A to Z, enoxaparin is an attractive alternative to heparin when used in combination with tirofiban and ASA SYNERGY will further address the efficacy of enoxaparin among patients treated with an early invasive strategy A to Z met its primary hypothesis: Among pts with NSTEMI ACS treated with tirofiban and ASA, Enoxaparin is non-inferior to UFH for the composite of Death, MI and Refractory Ischemia Based on the data from TIMI 11, ESSENCE, INTERACT and A to Z, enoxaparin is an attractive alternative to heparin when used in combination with tirofiban and ASA SYNERGY will further address the efficacy of enoxaparin among patients treated with an early invasive strategy