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

2. 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

3. 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

4. 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

5. 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

6. Baseline characteristics EUROPA PERSUADE n=1502 Placebo (mean ± SD) Perindopril (mean ± SD) (mean ± SD) Age (yrs) 62 ± 9 60 ± 9 Male (%) 818385 Weight (kg) 82 ± 13 83 ± 13 81 ± 12 SBP (mmHg) 140 ± 16 140 ± 15 137 ± 15 DBP (mmHg) 82 ± 8 81 ± 8 82 ± 8

7. Medical history & risks EUROPA PERSUADE n=1502 Placebo (%) Perindopril (%) (%) MI 686565 CABG 333032 PCI 262729 Stroke / TIA 563 PVD 12147 Hypertension 413827 Hyperlipidemia 616163

8. Clinical outcome 0 2 4 6 8 10 12 14 16 14.1 8.9 Primary Endpoint 11.1 6.5 Total Mortality 7.1 3.8 CV Mortality 8.9 6.0 MI 2.7 1.6 Stroke 2.5 1.3 Heart Failure 1.0 0.6 Doubl. Creatinine PERSUADEEUROPA(%)

9. RRR with perindopril Primary Endpoint Total Mortality CV mortality All MI Non Q MI Heart Failure Stroke 0.20.40.60.81.01.21.41.61.8 PerindoprilbetterPlacebobetter (%) RRR

10. Primary endpoint 2016 12 8 4 0 012345 Years from randomisation EUROPAplaceboperindopril placeboperindopril PERSUADE PERSUADE RRR 19% p=0.131 % CV death, MI and cardiac arrest

11. 012345 Years from randomisation 14 10 6 4 0 Fatal and non fatal MI placeboperindopril placeboperindopril EUROPA PERSUADE PERSUADE RRR 23% p=0.143 (%)

12. Heart Failure Years from randomisation placeboperindopril placeboperindopril PERSUADE RRR 46% p=0.06 PERSUADE EUROPA 012345 0 2 4 (%)

13. 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%

14. 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