Organization for the Assessment of Strategies for Ischemic Syndromes 6 (OASIS-6) Trial Presented at The American College of Cardiology Scientific Session 2006 Presented by Dr. Salim Yusuf OASIS - 6 Trial

www. Clinical trial results.org OASIS - 6 Trial: Background The goal of the trial was to evaluate treatment with fondaparinux compared with control (unfractionated heparin or placebo) among patients with STEMI.The goal of the trial was to evaluate treatment with fondaparinux compared with control (unfractionated heparin or placebo) among patients with STEMI. Patients were separated into Stratum 1 (control group inelligible for UFH treatment, in other words fondaparinux was compared to placebo) and Stratum 2 (active control group was UFH)Patients were separated into Stratum 1 (control group inelligible for UFH treatment, in other words fondaparinux was compared to placebo) and Stratum 2 (active control group was UFH) Also, there was a PCI substudy that assessed the efficacy of fondaparinux in Stratum 1 and Stratum 2 in the primary PCI setting.Also, there was a PCI substudy that assessed the efficacy of fondaparinux in Stratum 1 and Stratum 2 in the primary PCI setting. The goal of the trial was to evaluate treatment with fondaparinux compared with control (unfractionated heparin or placebo) among patients with STEMI.The goal of the trial was to evaluate treatment with fondaparinux compared with control (unfractionated heparin or placebo) among patients with STEMI. Patients were separated into Stratum 1 (control group inelligible for UFH treatment, in other words fondaparinux was compared to placebo) and Stratum 2 (active control group was UFH)Patients were separated into Stratum 1 (control group inelligible for UFH treatment, in other words fondaparinux was compared to placebo) and Stratum 2 (active control group was UFH) Also, there was a PCI substudy that assessed the efficacy of fondaparinux in Stratum 1 and Stratum 2 in the primary PCI setting.Also, there was a PCI substudy that assessed the efficacy of fondaparinux in Stratum 1 and Stratum 2 in the primary PCI setting. Presented at ACC 2006

www. Clinical trial results.org OASIS – 6 Trial: Study Design Presented at ACC 2006  Primary Endpoint: Composite of death or reinfarction at 30 days  Secondary Endpoint: Composite of death or reinfarction at 9 days and at final follow-up  Primary Endpoint: Composite of death or reinfarction at 30 days  Secondary Endpoint: Composite of death or reinfarction at 9 days and at final follow-up 12,092 patients presenting with STEMI within 24 hours of symptom onset (shortened to 12 hours of symptom onset midway through trial) Randomized. Blinded. Factorial. 28% female, mean age 62 years, mean follow-up 3-6 months 12,092 patients presenting with STEMI within 24 hours of symptom onset (shortened to 12 hours of symptom onset midway through trial) Randomized. Blinded. Factorial. 28% female, mean age 62 years, mean follow-up 3-6 months Stratum 1 (No UFH) Stratum 2 (UFH) Fondaparinux 2.5mg/day for up to 8 days or hospital discharge Fondaparinux 2.5mg/day for up to 8 days or hospital discharge Placebo Fondaparinux 2.5mg/day for up to 8 days or hospital discharge Fondaparinux 2.5mg/day for up to 8 days or hospital discharge UFH

www. Clinical trial results.org OASIS – 6 Trial: Primary Endpoint Presented at ACC 2006 The primary endpoint was lower in the fondaparinux group compared with the control group (9.7% vs.11.2%, HR 0.86, p=0.008)The primary endpoint was lower in the fondaparinux group compared with the control group (9.7% vs.11.2%, HR 0.86, p=0.008) The results were similar at 9 days (HR 0.83, p=0.003) and at study end (HR 0.88, p=0.008)The results were similar at 9 days (HR 0.83, p=0.003) and at study end (HR 0.88, p=0.008) Primary Endpoint: Death/Reinfarction (%) p=0.008 p=0.003 p=0.008 Frequency

www. Clinical trial results.org OASIS – 6 Trial: Primary Endpoint (cont.) Presented at ACC 2006 Reduction in Death/MI: Stratum 1 (No UFH indicated) p<0.05 Reduction in Death/MI: Stratum 2 (UFH Indicated) p=NS The reduction in the primary endpoint at 30 days in the Fondaparinux group was driven by Stratum 1, where death/MI occurred less frequently among Fonda pts than Placebo (11.2 vs. 14%, HR 0.79, p<0.05) The reduction in the primary endpoint at 30 days in the Fondaparinux group was driven by Stratum 1, where death/MI occurred less frequently among Fonda pts than Placebo (11.2 vs. 14%, HR 0.79, p<0.05) There was no difference in Stratum 2, comparing those patients who received Fondaparinux vs those who received UFH (8.3% vs. 8.7%, HR 0.96, p=NS) There was no difference in Stratum 2, comparing those patients who received Fondaparinux vs those who received UFH (8.3% vs. 8.7%, HR 0.96, p=NS) p=0.97

www. Clinical trial results.org OASIS – 6 Trial: Primary Composite Endpoint Among the components of the composite at 30 days, mortality was lower in the fondaparinux group compared to the control group (7.8% vs. 8.9%, HR 0.87, p=0.03).Among the components of the composite at 30 days, mortality was lower in the fondaparinux group compared to the control group (7.8% vs. 8.9%, HR 0.87, p=0.03). Reinfarction was also lower in the fondaparinux group compared to the control group (2.5% vs. 3.0% HR 0.81, p=0.06).Reinfarction was also lower in the fondaparinux group compared to the control group (2.5% vs. 3.0% HR 0.81, p=0.06). Presented at ACC 2006 Components of Primary Composite Endpoint (%) p=0.03 p=0.06

www. Clinical trial results.org OASIS - 6 Trial: PCI Substudy at 30 Days Presented at ACC 2006 There was no difference in the primary endpoint for patients who were managed with primary PCI (6.1% vs 5.1%, p=0.19).There was no difference in the primary endpoint for patients who were managed with primary PCI (6.1% vs 5.1%, p=0.19). Guiding catheter thrombosis in the primary PCI cohort occurred more often with fondaparinux compared with control (n=22 vs. n=0, p<0.001)Guiding catheter thrombosis in the primary PCI cohort occurred more often with fondaparinux compared with control (n=22 vs. n=0, p<0.001) Primary Endpoint of Death or MI in PCI Cohort (%) p=0.19

www. Clinical trial results.org OASIS - 6 Trial: PCI Substudy (cont.) Presented at ACC 2006 There was no difference in severe bleeding at 9 days by treatment groupThere was no difference in severe bleeding at 9 days by treatment group (1.0% Fondaparinux vs. 1.3% control, p=NS) Intracranial hemorrhage occurred in 0.2% in each groupIntracranial hemorrhage occurred in 0.2% in each group Severe Bleeding at 9 days (%) p=NS

www. Clinical trial results.org OASIS - 6 Trial: PCI Substudy (cont.) Presented at ACC 2006 There was a higher instance of guiding catheter thrombosis in the PCI cohort treated with fondaparinux compared to control (n=22 vs. n=0, p<0.001)There was a higher instance of guiding catheter thrombosis in the PCI cohort treated with fondaparinux compared to control (n=22 vs. n=0, p<0.001) Guiding Catheter Thrombosis p<0.001

www. Clinical trial results.org OASIS - 6 Trial: PCI Substudy (cont.) Presented at ACC 2006 Coronary complications occurred in more patients treated with fondaparinux compared to control (n=270 vs. n=225, p=0.04)Coronary complications occurred in more patients treated with fondaparinux compared to control (n=270 vs. n=225, p=0.04) Coronary complications include abrupt closure, no reflow, dissection, new angiographic thrombus, perforation, or catheter thrombusCoronary complications include abrupt closure, no reflow, dissection, new angiographic thrombus, perforation, or catheter thrombus Coronary Complications p=0.04

www. Clinical trial results.org OASIS – 6 Trial: Conclusions The benefit of Fondaparinux was confined to patients in Stratum 1 where placebo or no antithrombin was administeredThe benefit of Fondaparinux was confined to patients in Stratum 1 where placebo or no antithrombin was administered Fondaparinux was not superior to active control UFHFondaparinux was not superior to active control UFH Fondaparinux was associated with a hazard in those patients who underwent PCI including guiding catheter thrombosisFondaparinux was associated with a hazard in those patients who underwent PCI including guiding catheter thrombosis The benefit of Fondaparinux was confined to patients in Stratum 1 where placebo or no antithrombin was administeredThe benefit of Fondaparinux was confined to patients in Stratum 1 where placebo or no antithrombin was administered Fondaparinux was not superior to active control UFHFondaparinux was not superior to active control UFH Fondaparinux was associated with a hazard in those patients who underwent PCI including guiding catheter thrombosisFondaparinux was associated with a hazard in those patients who underwent PCI including guiding catheter thrombosis Presented at ACC 2006