K Fox, W Remme, C Daly, M Bertrand, R Ferrari, M Simoons On behalf of the EUROPA investigators. The diabetic sub study of

ACE inhibitor therapy of proven benefit in secondary prevention in myocardial infarction and heart failure EUROPA concluded that perindopril was also beneficial in patients with CAD, without heart failure and with broad range of risk Within the coronary disease population, diabetics are a subpopulation at high risk ACE inhibitor therapy of proven benefit in secondary prevention in myocardial infarction and heart failure EUROPA concluded that perindopril was also beneficial in patients with CAD, without heart failure and with broad range of risk Within the coronary disease population, diabetics are a subpopulation at high risk Background

Aim of the study To investigate the effect of the ACE inhibitor perindopril 8 mg once daily added to standard therapy on cardiovascular events in diabetic patients with documented coronary disease To investigate the effect of the ACE inhibitor perindopril 8 mg once daily added to standard therapy on cardiovascular events in diabetic patients with documented coronary disease

Study endpoints CV mortality + non fatal MI + cardiac arrest CV mortality + non fatal MI + cardiac arrest Fatal and non-fatal MI Fatal and non-fatal MI Non-fatal MI Non-fatal MI Stroke Stroke Hospitalisation for heart failure Hospitalisation for heart failure Development of renal failure Development of renal failure Primary endpoint Secondary endpoints

Patient population Known diabetes at randomisation: n=1502 Male or female > 18 years of age Documented coronary disease Not scheduled for revascularisation No clinical signs of heart failure

Baseline characteristics EUROPA PERSUADE n=1502 Placebo (mean ± SD) Perindopril (mean ± SD) (mean ± SD) Age (yrs) 62 ± 9 60 ± 9 Male (%) Weight (kg) 82 ± ± ± 12 SBP (mmHg) 140 ± ± ± 15 DBP (mmHg) 82 ± 8 81 ± 8 82 ± 8

Medical history & risks EUROPA PERSUADE n=1502 Placebo (%) Perindopril (%) (%) MI CABG PCI Stroke / TIA 563 PVD Hypertension Hyperlipidemia

Clinical outcome Primary Endpoint Total Mortality CV Mortality MI Stroke Heart Failure Doubl. Creatinine PERSUADEEUROPA(%)

RRR with perindopril Primary Endpoint Total Mortality CV mortality All MI Non Q MI Heart Failure Stroke PerindoprilbetterPlacebobetter (%) RRR

Primary endpoint Years from randomisation EUROPAplaceboperindopril placeboperindopril PERSUADE PERSUADE RRR 19% p=0.131 % CV death, MI and cardiac arrest

Years from randomisation Fatal and non fatal MI placeboperindopril placeboperindopril EUROPA PERSUADE PERSUADE RRR 23% p=0.143 (%)

Heart Failure Years from randomisation placeboperindopril placeboperindopril PERSUADE RRR 46% p=0.06 PERSUADE EUROPA (%)

Summary of results In PERSUADE, the relative risk reduction with perindopril on 1° and 2° endpoints was similar to that in the main EUROPA population Primary endpoint RRR 19% Fatal and nonfatal MI RRR 23% Heart Failure RRR 46%

Conclusion Perindopril 8 mg once daily reduces cardiovascular events in patients with coronary disease and diabetes NNT to prevent one cardiovascular death or nonfatal myocardial infarction is just 27 patients over 4 years Perindopril 8 mg once daily reduces cardiovascular events in patients with coronary disease and diabetes NNT to prevent one cardiovascular death or nonfatal myocardial infarction is just 27 patients over 4 years