1. Impact of Low-molecular-weight Heparin (Reviparin) on Mortality, Reinfarction, and Stroke in Patients with Acute MI CREATE-ECLA - Reviparin Presented at: American Heart Association Scientific Sessions 2004 Presented by: Dr. S.D. Yusuf

2. www. Clinical trial results.org Reviparin (low-molecular-weight heparin) Subcutaneous injections for 7 days Weight-adjusted doses: <50 kg 3436 IU 50-75 kg 5153 IU >75 kg 6871 IU  n=7,780 Mean onset-to-treatment = 4.9 hr Reviparin (low-molecular-weight heparin) Subcutaneous injections for 7 days Weight-adjusted doses: <50 kg 3436 IU 50-75 kg 5153 IU >75 kg 6871 IU  n=7,780 Mean onset-to-treatment = 4.9 hr Primary Endpoints: Death, MI, or stroke at 7 days; death, MI, stroke, or recurrent ischemia with ECG changes at 7 days. Secondary Endpoints: above endpoints at 30 days Primary Endpoints: Death, MI, or stroke at 7 days; death, MI, stroke, or recurrent ischemia with ECG changes at 7 days. Secondary Endpoints: above endpoints at 30 days CREATE-ECLA - Reviparin Presented at AHA 2004 15,570 acute MI patients presenting within 12 hours of symptom onset Enrolled exclusively in India and China 6% received PCI, 73% thrombolytic therapy (primarily streptokinase and urokinase) 97% Aspirin, 72% ACE inhibitors, 66% beta-blockers, 66% lipid-lowering therapy, 55% clopidogrel Also randomized to GIK or control – results presented separately 15,570 acute MI patients presenting within 12 hours of symptom onset Enrolled exclusively in India and China 6% received PCI, 73% thrombolytic therapy (primarily streptokinase and urokinase) 97% Aspirin, 72% ACE inhibitors, 66% beta-blockers, 66% lipid-lowering therapy, 55% clopidogrel Also randomized to GIK or control – results presented separately Placebo  n=7,790 Mean onset-to-treatment = 4.8 hr Placebo  n=7,790 Mean onset-to-treatment = 4.8 hr

3. www. Clinical trial results.org CREATE-ECLA –Reviparin: 7-day results % Presented at AHA 2004 p=0.0049 p=0.0039 Death/MI/stroke and Death/MI/stroke/ischemia at 7 days The primary composite endpoints of 7-day death/MI/stroke and death/MI/stroke/ischemia were significantly lower in the Reviparin group compared to the placebo group

4. www. Clinical trial results.org CREATE-ECLA –Reviparin 7-day results % Presented at AHA 2004 Treatment with Reviparin was associated with a significant reduction in the individual primary endpoints of death and recurrent MI at 7 days. The two treatments were not significantly different in the occurrence of stroke. p=0.0357 p= NS p=0.018

5. www. Clinical trial results.org CREATE-ECLA –Reviparin: 30-day results % Presented at AHA 2004 p=0.0014 p=0.0016 Death/MI/stroke and Death/MI/stroke/ischemia at 30 days The secondary composite endpoints of 30-day death/MI/stroke and death/MI/stroke/ischemia were significantly lower in the Reviparin group compared to the placebo group. The individual endpoints of Death and MI were also significantly lower in the Reviparin group at 30 days.

6. www. Clinical trial results.org CREATE-ECLA –Reviparin: Safety % Presented at AHA 2004 p=<0.001 Bleeding at 7 days Life-threatening bleeding and major bleeding and life- threatening bleeding alone at 7 days were both significantly higher with Reviparin compared with placebo

7. www. Clinical trial results.org CREATE-ECLA –Reviparin: Summary Among acute MI patients presenting within 12 hours of onset of symptoms, treatment with the low- molecular-weight heparin reviparin was associated with a significant reduction in the primary composite endpoints of 7-day death/MI/stroke and death/MI/stroke/ischemia compared with placebo. The results were maintained at 30-days The reduced primary composite endpoints at both 7 and 30 days were due to lower individual endpoints of death and recurrent MI in the reviparin group; the two treatments were not significantly different in incidence of stroke Small but significant increases in 7-day life-threatening bleeding/major bleeding and life-threatening bleeding alone occurred in the reviparin arm There was a significant association between time-to-treatment and efficacy, with no effect seen in patients treated after 8 hours from symptom onset. Treatment occurred entirely in India and China and differed from standard Western practice in several ways, including a reduced number of patients receiving primary PCI and reliance on thrombolytics not often used in the US (streptokinase and urokinase) The study is the first large randomized trial to show a significant reduction in mortality with a low molecular weight heparinoid drug when given in addition to reperfusion therapy and aspirin in patients with acute MI The ongoing EXTRACT trial is looking for a similar reduction in mortality in acute MI patients treated with another low-molecular-weight heparin, enoxaparin Among acute MI patients presenting within 12 hours of onset of symptoms, treatment with the low- molecular-weight heparin reviparin was associated with a significant reduction in the primary composite endpoints of 7-day death/MI/stroke and death/MI/stroke/ischemia compared with placebo. The results were maintained at 30-days The reduced primary composite endpoints at both 7 and 30 days were due to lower individual endpoints of death and recurrent MI in the reviparin group; the two treatments were not significantly different in incidence of stroke Small but significant increases in 7-day life-threatening bleeding/major bleeding and life-threatening bleeding alone occurred in the reviparin arm There was a significant association between time-to-treatment and efficacy, with no effect seen in patients treated after 8 hours from symptom onset. Treatment occurred entirely in India and China and differed from standard Western practice in several ways, including a reduced number of patients receiving primary PCI and reliance on thrombolytics not often used in the US (streptokinase and urokinase) The study is the first large randomized trial to show a significant reduction in mortality with a low molecular weight heparinoid drug when given in addition to reperfusion therapy and aspirin in patients with acute MI The ongoing EXTRACT trial is looking for a similar reduction in mortality in acute MI patients treated with another low-molecular-weight heparin, enoxaparin