Clinical implications

Burden of coronary disease 56 millions deaths worldwide in millions deaths worldwide in % due to CV disease (~ 16 millions) 29% due to CV disease (~ 16 millions) (37% are foreseen in 2020) (37% are foreseen in 2020) 20 millions of people in the EU have coronary disease 20 millions of people in the EU have coronary disease 56 millions deaths worldwide in millions deaths worldwide in % due to CV disease (~ 16 millions) 29% due to CV disease (~ 16 millions) (37% are foreseen in 2020) (37% are foreseen in 2020) 20 millions of people in the EU have coronary disease 20 millions of people in the EU have coronary disease

Silent ischemia Stable Angina Unstable angina MI Heart failure Sudden death Coronary Disease Clinical expression of coronary disease

Benefit of ACE inhibition CV death, MI Card. arrest CV death MICard.arrest Perindopril Placebo Death %

Absolute benefits Perindopril 8 mg once a day prevents one cardiovascular death, non fatal MI or cardiac arrest among every 50 patients with coronary disease treated for 4 years Perindopril 8 mg once a day prevents one cardiovascular death, non fatal MI or cardiac arrest among every 50 patients with coronary disease treated for 4 years For a country of 60 million inhabitants, this means that perindopril over a 4 year period will stop heart attacks or CV deaths

% Death, MI, Cardiac arrest Age, gender, previous MI, previous CABG/PCI, PVD or stroke, hypertension, diabetes, smoking, hyperchol., lipid lowering,  -blockers. Low Medium High risk %

Myocardial infarction 64% of patients had an history of MI 20% within 1 year of the MI 20% within 1 year of the MI 47% between 1 and 5 years after MI 47% between 1 and 5 years after MI 33% more than 5 years after MI 33% more than 5 years after MI 64% of patients had an history of MI 20% within 1 year of the MI 20% within 1 year of the MI 47% between 1 and 5 years after MI 47% between 1 and 5 years after MI 33% more than 5 years after MI 33% more than 5 years after MI

92% patients on platelet inhibitors Sub-groups analysis RRR (%) Lipid lowering drug Perindopril better Placebo better No lipid lowering drug  -blockers No  -blockers Calcium blockers No calcium blockers

Interaction A formal interaction analysis was performed for the effect of perindopril in relation to:  -blockers  -blockers Lipid lowering drugs Lipid lowering drugs Calcium antagonists Calcium antagonists A formal interaction analysis was performed for the effect of perindopril in relation to:  -blockers  -blockers Lipid lowering drugs Lipid lowering drugs Calcium antagonists Calcium antagonists Interaction effect was not significant in all 3 analyses The treatment effect of perindopril was independent of the other drugs

HOPE vs. EUROPA Study population HOPEEUROPA Age (yrs) 6660 Female gender (%) 2715 Known CAD (%) Previous MI (%) 5365 PVD (%) 437 Stroke/TIA (%) 113 Diabetes (%) 3812 Hypertension (%) 4727 Hypercholesterolemia (%) 6663

BaselineHOPEEUROPA Antiplatelet drugs* 76 % 92 %  -blockers 39 % 62 % Lipid lowering drugs 29 % 58 % * Mostly aspirin More extensive treatment in EUROPA than in HOPE HOPE vs. EUROPA

HOPEEUROPA Total mortality 12.2% 7.4 % CV mortality 8.1%4.4% Q wave MI 3.2%2.1% Major annual event rates : 50 to 80 % higher in HOPE Placebo outcomes standardised for 4.5 yrs FU HOPE vs. EUROPA

EUROPA HOPE SOLVD (prev) SOLVD SAVE AIRE TRACE ALL CAD PATIENTS Benefits for all coronary artery disease patients

Summary of results In EUROPA, the largest and longest trial of stable, optimally treated CAD patients, perindopril 8 mg/d significantly reduced: CV mortality + non fatal MI + cardiac arrest: 20% CV mortality + non fatal MI + cardiac arrest: 20% CV mortality and non fatal MI: 19% CV mortality and non fatal MI: 19% Fatal + non fatal MI: 24% Fatal + non fatal MI: 24% Heart failure: 39% Heart failure: 39%

Benefits of results Benefits occurred on top of recommended therapy (92% platelet inhibitors, 58% lipid lowering drugs, 62%  -blockers) and are consistent across predefined sub-groups Benefits occurred on top of recommended therapy (92% platelet inhibitors, 58% lipid lowering drugs, 62%  -blockers) and are consistent across predefined sub-groups Perindopril should be considered for chronic therapy in all patients with coronary disease Perindopril should be considered for chronic therapy in all patients with coronary disease