Perindopril Remodeling in Elderly with Acute Myocardial Infarction

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

2. PREAMI 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 Placebo 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 ESC 2005

3. 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

4. PREAMI: Secondary Endpoints Cardiac Remodeling p < 0.001 • 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. % pts With Adverse Remodeling ESC 2005

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

6. 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. ESC 2005