Effects of PG , a Matrix Metalloproteinase Inhibitor to Prevent Left Ventricular Remodeling After Acute Myocardial Infarction Effects of PG , a Matrix Metalloproteinase Inhibitor to Prevent Left Ventricular Remodeling After Acute Myocardial Infarction Presented at American College of Cardiology Scientific Sessions 2005 Presented by Dr. W Douglas Weaver PREMIER Trial

www. Clinical trial results.org Endpoints (90 days):  Primary: Left ventricular end diastolic volume index (LVEDVI) change  Secondary: LVEDVI change at 30 days; LVESV, LV ejection fraction and LV sphericity changes; clinical events Endpoints (90 days):  Primary: Left ventricular end diastolic volume index (LVEDVI) change  Secondary: LVEDVI change at 30 days; LVESV, LV ejection fraction and LV sphericity changes; clinical events PREMIER Trial Presented at ACC Scientific Sessions patients with ST elevation myocardial infarction (MI) and signs of heart failure. Age years; first ST segment elevation MI; cardiac troponin or CKMB ≥3 times upper limit of normal; echocardiogram with an ejection fraction of 15-40% within 48 hours of MI. Randomized, Blinded 253 patients with ST elevation myocardial infarction (MI) and signs of heart failure. Age years; first ST segment elevation MI; cardiac troponin or CKMB ≥3 times upper limit of normal; echocardiogram with an ejection fraction of 15-40% within 48 hours of MI. Randomized, Blinded PG Matrix Metalloproteinase (MMP) Inhibitor 200 mg twice daily for 90 days n=125 PG Matrix Metalloproteinase (MMP) Inhibitor 200 mg twice daily for 90 days n=125 Placebo n=128 Placebo n=128

www. Clinical trial results.org Presented at ACC Scientific Sessions 2005 PREMIER Trial The change in LVEDVI did not differ by treatment group. The majority of patients were enrolled in Poland (n=173), with 45 patients in Canada and 35 patients in the US. Randomized treatment was complete through 90 days in 79% of patients in the PG group and 84% of patients in the placebo group. Discontinuation due to adverse event occurred in 6% of the PG group and 9% of the placebo group. Baseline characteristics were well-balanced by treatment group, with 80% of patients having an anterior MI and 90% treated with primary PCI. LVEDVI at 90 days p=0.42

www. Clinical trial results.org Presented at ACC Scientific Sessions 2005 PREMIER Trial The change in LVEDVI did not differ by treatment group.The change in LVEDVI did not differ by treatment group. There was also no difference in change in LV end diastolic volume, LV end systolic volume, LV ejection fraction, or sphericity index.There was also no difference in change in LV end diastolic volume, LV end systolic volume, LV ejection fraction, or sphericity index. There was also no difference in clinical events at 90 days, including death (3% vs 1%, p=0.21), severe heart failure (8% vs 7%, p=0.82), reinfarction (6% vs 2%, p=0.21) or recurrent ischemia (1% each, p=1.0). The frequency of serious adverse events was similar in both groups.There was also no difference in clinical events at 90 days, including death (3% vs 1%, p=0.21), severe heart failure (8% vs 7%, p=0.82), reinfarction (6% vs 2%, p=0.21) or recurrent ischemia (1% each, p=1.0). The frequency of serious adverse events was similar in both groups. LV End Diastolic Volume p=0.44 LV End Systolic Volume p=0.19 LV Ejection Fraction p=0.08 Sphericity Index p=0.10 PG Placebo

www. Clinical trial results.org Among patients with ST elevation myocardial infarction and signs of heart failure, treatment with the matrix metalloproteinase inhibitor PG was not associated with an improvement in left ventricular end diastolic volume index at 90 days or other measures of LV remodeling compared with placebo.Among patients with ST elevation myocardial infarction and signs of heart failure, treatment with the matrix metalloproteinase inhibitor PG was not associated with an improvement in left ventricular end diastolic volume index at 90 days or other measures of LV remodeling compared with placebo. The present inhibitor was designed to have high affinity for MMP 13 and low affinity for MMP 1 and 7. It is possible that targeting of other MMPs may have different therapeutic effects, or that timing of the therapy may be more beneficial earlier post-MI.The present inhibitor was designed to have high affinity for MMP 13 and low affinity for MMP 1 and 7. It is possible that targeting of other MMPs may have different therapeutic effects, or that timing of the therapy may be more beneficial earlier post-MI. Presented at ACC Scientific Sessions 2005 PREMIER Trial: Summary