Perindopril Remodeling in Elderly with Acute Myocardial Infarction PREAMIPREAMI Presented at The European Society of Cardiology Hot Line Session, September 2005 Presented by Dr. Roberto Ferrari

www. Clinical trial results.org Perindopril (4 mg for 1 month, followed by 8 mg for 11 months) Standard medical therapy; echocardiography at 6 and 12 months Perindopril (4 mg for 1 month, followed by 8 mg for 11 months) Standard medical therapy; echocardiography at 6 and 12 months Endpoints:  Primary – Composite of death, hospitalization for heart failure, or adverse cardiac remodeling, defined as a >8% increase in LV end diastolic volume  Secondary – Individual components of the primary endpoint; LV end diastolic volume; cardiovascular death, hospitalization for reinfarction or angina; CABG or PCI Endpoints:  Primary – Composite of death, hospitalization for heart failure, or adverse cardiac remodeling, defined as a >8% increase in LV end diastolic volume  Secondary – Individual components of the primary endpoint; LV end diastolic volume; cardiovascular death, hospitalization for reinfarction or angina; CABG or PCI PREAMI ESC 2005 Placebo Standard medical therapy; echocardiography at 6 and 12 months Placebo Standard medical therapy; echocardiography at 6 and 12 months 1259 patients, Acute myocardial infarction in prior 7-20 days, age ≥65 years, LV ejection fraction ≥40%, good apical views of LV at baseline echo

www. Clinical trial results.org PREAMI: Primary endpoint There was a 38% relative risk reduction in the primary composite endpoint of CV death, recurrent MI, or stroke following PCI in the Perindopril group compared to the placebo group (p<0.001). ESC 2005 EndpointRelative risk reduction with Perindoprilp-value Death/HF hospitalization/remodeling38<0.001 Total mortality00.9 Hospitalization for heart failure Remodeling46<0.001

www. Clinical trial results.org PREAMI: Secondary Endpoints The reduction in the primary composite endpoint of death, hospitalization for heart failure, or heart remodeling was driven by a significant reduction in adverse cardiac remodeling in the treatment group compared to the placebo group. Differences in mortality and hospitalization for heart failure were not significant between groups. The reduction in the primary composite endpoint of death, hospitalization for heart failure, or heart remodeling was driven by a significant reduction in adverse cardiac remodeling in the treatment group compared to the placebo group. Differences in mortality and hospitalization for heart failure were not significant between groups. Cardiac Remodeling p < ESC 2005 % pts With Adverse Remodeling

www. Clinical trial results.org PREAMI: Secondary Endpoints LV end diastolic volume was lower at 12 months in the perindopril group compared with placebo. 12 Month LV End Diastolic Volume ESC 2005 Diastolic Volume (cc)

www. Clinical trial results.org PREAMI: Summary Among elderly patients post-MI with preserved LV function, addition of the ACE-inhibitor Perindopril to conventional therapy was associated with a reduction in the primary composite endpoint of death, hospitalization for heart failure, or adverse heart remodeling, driven primarily by the reduction in adverse remodeling, compared with placebo at 12 month follow-up. These data further support the prior trials that have demonstrated the benefit of ACE-inhibitor therapy in patients with coronary artery disease. In the EUROPA trial, the benefit of long-term perindopril therapy on cardiovascular death or MI was demonstrated among patients with low- risk, stable coronary artery disease syndromes, including post-MI. The present trial further defines these benefits among a cohort of elderly patients with preserved LV function. While no clinical benefit was observed in PREAMI, the sample size and duration of therapy may have been insufficient to detect such a difference. Substudies from the EUROPA trial suggested a mechanism of benefit via blood pressure reduction and anti-atherosclerotic improvements such as endothelial function and nitric oxide increase. The PREAMI trial suggests cardiac remodeling may also play a role in the mechanism of benefit with perindopril post-MI. The study also demonstrates that LV remodeling can occur post-MI, despite small initial infarct size. Among elderly patients post-MI with preserved LV function, addition of the ACE-inhibitor Perindopril to conventional therapy was associated with a reduction in the primary composite endpoint of death, hospitalization for heart failure, or adverse heart remodeling, driven primarily by the reduction in adverse remodeling, compared with placebo at 12 month follow-up. These data further support the prior trials that have demonstrated the benefit of ACE-inhibitor therapy in patients with coronary artery disease. In the EUROPA trial, the benefit of long-term perindopril therapy on cardiovascular death or MI was demonstrated among patients with low- risk, stable coronary artery disease syndromes, including post-MI. The present trial further defines these benefits among a cohort of elderly patients with preserved LV function. While no clinical benefit was observed in PREAMI, the sample size and duration of therapy may have been insufficient to detect such a difference. Substudies from the EUROPA trial suggested a mechanism of benefit via blood pressure reduction and anti-atherosclerotic improvements such as endothelial function and nitric oxide increase. The PREAMI trial suggests cardiac remodeling may also play a role in the mechanism of benefit with perindopril post-MI. The study also demonstrates that LV remodeling can occur post-MI, despite small initial infarct size. ESC 2005