1. Prevention of Events with Angiotensin Converting Enzyme Inhibition (PEACE) Trial PEACE Trial Presented at The American Heart Association Scientific Sessions 2004 Presented by Dr. M. Pheffer

2. www. Clinical trial results.org ACE Inhibitor Trandolapril 4mg/day At 1 year, Trandolapril or open-label ACE inhibitor taken by 81.9% At 3 years, 74.5% n=4,158 ACE Inhibitor Trandolapril 4mg/day At 1 year, Trandolapril or open-label ACE inhibitor taken by 81.9% At 3 years, 74.5% n=4,158 Primary Endpoint:  Composite of cardiac death, MI, or revascularization at a mean follow-up of 4.8 years Primary Endpoint:  Composite of cardiac death, MI, or revascularization at a mean follow-up of 4.8 years PEACE Trial Presented at AHA 2004 Placebo At 1 year, 1.5% of patients on Ace inhibitor At 3 years, 8.3%  n=4,132 Placebo At 1 year, 1.5% of patients on Ace inhibitor At 3 years, 8.3%  n=4,132 8,290 patients with stable coronary artery disease without heart failure MI, CABG, or PCI at least 3 mo prior to enrollment, normal LV wall motion w/ EF>40% 82% male, mean age 64 years 90% received Aspirin, 60% beta-blockers, 70% lipid-lowering therapy 8,290 patients with stable coronary artery disease without heart failure MI, CABG, or PCI at least 3 mo prior to enrollment, normal LV wall motion w/ EF>40% 82% male, mean age 64 years 90% received Aspirin, 60% beta-blockers, 70% lipid-lowering therapy

3. www. Clinical trial results.org PEACE Trial: Primary endpoint The primary composite endpoint of cardiovascular death, MI, and revascularization was equal between the Trandolapril and Placebo groups at a mean follow-up of 4.8 years The primary endpoint was also equivalent in all analyzed subgroups Primary Composite of cardiovascular death, nonfatal MI, and coronary revascularization p = 0.43 Presented at AHA 2004

4. www. Clinical trial results.org PEACE Trial: Primary Endpoint % Presented at AHA 2004 p=0.67 p=1.00 p=0.24 p=0.65 The individual components of the primary endpoint were also equivalent in the Trandolapril and placebo groups

5. www. Clinical trial results.org PEACE Trial: All Death A slight reduction in all-cause death seen in the Trandolapril arm was not statistically significant All-Cause Death p = 0.13 Presented at AHA 2004

6. www. Clinical trial results.org PEACE Trial New onset diabetes p = 0.01 CHF as primary cause of hospitalization or death p = 0.02 % % Presented at AHA 2004 CHF as the primary cause of hospitalization or death and new-onset diabetes were both significantly lower in the trandolapril group. Neither analysis was a primary or secondary endpoint.

7. www. Clinical trial results.org PEACE Trial: Safety There was a significantly higher incidence of side effects leading to drug discontinuation in the Trandolapril group. The Trandolapril group also had significant increases in cough and syncope Side effects leading to discontinuation p < 0.001 Presented at AHA 2004

8. www. Clinical trial results.org PEACE Trial: Summary Among patients with stable coronary artery disease and no heart failure, there was no difference in the primary composite endpoint of cardiovascular death, nonfatal MI, and coronary revascularization with the ACE inhibitor trandolapril or placebo. All individual components of the primary endpoint were equivalent between the two groups. A retrospective analysis of new onset diabetes and CHF as the primary cause of hospitalization or death was found both to be lower in the trandolapril group. Trandolapril was associated with a significantly higher incidence of side effects leading to drug discontinuation. Additionally, cough and syncope were each significantly higher in the trandolapril cohort. The lack of benefit from ACE inhibitor therapy seen in this trial differs from the results of several previous trials including the HOPE and EUROPA trials, which showed significantly lower incidences of cardiovascular death, MI, stroke, and cardiac arrest in patients treated with ACE inhibitors than in those treated with placebo. A possible reason for the lack of benefit with trandolapril could be that most patients were more aggressively managed for risk factors with lipid-lowering medication and previous revascularization. In accordance with this hypothesis, the PEACE trial had a lower event rate than the EUROPA and HOPE trials. Among patients with stable coronary artery disease and no heart failure, there was no difference in the primary composite endpoint of cardiovascular death, nonfatal MI, and coronary revascularization with the ACE inhibitor trandolapril or placebo. All individual components of the primary endpoint were equivalent between the two groups. A retrospective analysis of new onset diabetes and CHF as the primary cause of hospitalization or death was found both to be lower in the trandolapril group. Trandolapril was associated with a significantly higher incidence of side effects leading to drug discontinuation. Additionally, cough and syncope were each significantly higher in the trandolapril cohort. The lack of benefit from ACE inhibitor therapy seen in this trial differs from the results of several previous trials including the HOPE and EUROPA trials, which showed significantly lower incidences of cardiovascular death, MI, stroke, and cardiac arrest in patients treated with ACE inhibitors than in those treated with placebo. A possible reason for the lack of benefit with trandolapril could be that most patients were more aggressively managed for risk factors with lipid-lowering medication and previous revascularization. In accordance with this hypothesis, the PEACE trial had a lower event rate than the EUROPA and HOPE trials.