Baseline characteristicsBaseline characteristics

Patient flowPatient flow

CompletedCompleted6 1076 107

CompletedCompleted6 1086 108

PerindoprilPerindopril6 1106 110

PlaceboPlacebo6 1086 108

RandomisedRandomised12 21812 218

Not randomisedNot randomised1 4371 437

RegisteredRegistered13 65513 655

424 centres :424 centres : 12 218 patients 12 218 patients

102102

176176141141

130130

5757

12511251

21762176

115115

9494

300300

399399

285285

511511890890

1717

2222

20682068

17721772

277277

134134

209209

6565

197197

830830

Not randomisedNot randomised

Overall: 1 437 of 13 655 ptsOverall: 1 437 of 13 655 pts 10.510.5

IntoleranceIntolerance

HypotensionHypotension

Creatinine/Potassium riseCreatinine/Potassium rise

Poor compliancePoor compliance

Major clinical eventMajor clinical event

Non medical reasonsNon medical reasons

UnspecifiedUnspecified

2.42.4

2.12.1

1.11.1

0.60.6

0.50.5

0.50.5

3.33.3

%%

PerindoprilPerindopril(mean (mean SD) SD)

Placebo Placebo (mean (mean SD) SD)

Age Age (yrs)(yrs) 60 60 9 9 60 60 9 9

Male Male (%)(%) 86 86 8585

Weight Weight (kg)(kg) 81 81 12 12 80 80 12 12

HR HR (bpm)(bpm) 68 68 10 10 68 68 10 10

SBP SBP (mmHg)(mmHg) 137 137 16 16 137 137 15 15

DBP DBP (mmHg)(mmHg) 82 82 8 8 82 82 8 8

Baseline characteristicsBaseline characteristics

PerindoprilPerindopril(%)(%)

PlaceboPlacebo (%)(%)

Myocardial infarctionMyocardial infarction 64.964.9 64.764.7

RevascularisationRevascularisation 54.754.7 55.255.2

Stroke / TIAStroke / TIA 3.43.4 3.33.3

Heart failureHeart failure 1.31.3 1.21.2

Peripheral vascular Peripheral vascular diseasedisease 7.17.1 7.47.4

Medical historyMedical history

PerindoprilPerindopril(%)(%)

PlaceboPlacebo

(%)(%)

HypertensionHypertension 27.027.0 27.227.2

Diabetes mellitusDiabetes mellitus 11.811.8 12.812.8

HypercholesterolaemiaHypercholesterolaemia 63.363.3 63.363.3

Current smokerCurrent smoker 15.415.4 15.115.1

Risk factorsRisk factors

Perindopril Perindopril (%)(%)

PlaceboPlacebo(%)(%)

Platelet inhibitorsPlatelet inhibitors 91.991.9 92.792.7

-blockers-blockers 62.062.0 61.361.3

Lipid lowering drugsLipid lowering drugs 57.857.8 57.357.3

NitratesNitrates 42.842.8 43.043.0

Ca-blockersCa-blockers 31.731.7 31.031.0

DiureticsDiuretics 9.19.1 9.49.4

Oral anticoagulantsOral anticoagulants 4.44.4 4.24.2

Baseline medicationBaseline medication

ResultsResults

Primary endpointPrimary endpoint

% CV death, MI or cardiac arrest% CV death, MI or cardiac arrest

Placebo annual event rate: 2.4%Placebo annual event rate: 2.4%

Perindopril Perindopril

PlaceboPlacebo

p = 0.0003p = 0.0003RRR: 20%RRR: 20%

YearsYears00

22

44

66

88

1010

1212

1414

00 11 22 33 44 55

Primary Primary and first secondary endpointand first secondary endpoint

0.50.5 1.01.0 2.02.0

2020

1414

2222

4646

1414

RRR RRR (%)(%)PerindoprilPerindoprilbetterbetter

PlaceboPlacebobetterbetter

CV mortality, MI, CACV mortality, MI, CA

CV mortalityCV mortality

Non fatal MINon fatal MI

Cardiac arrestCardiac arrest

Total mortality, MI, UAP,CATotal mortality, MI, UAP,CA

Sub-groups analysisSub-groups analysis

RRR RRR (%)(%)

0.50.5 1.01.0 2.02.0

Perindopril betterPerindopril better Placebo betterPlacebo better

Previous MIPrevious MI

No previous MINo previous MI

22.422.4

12.112.1

Age Age 56 yrs 56 yrs

Age 57 - 65Age 57 - 65

Age > 65 yrsAge > 65 yrs

27.327.3

14.314.3

18.218.2

MaleMale

FemaleFemale

19.319.3

22.022.0

Sub-groups analysisSub-groups analysis

0.50.5 1.01.0 2.02.0

HypertensionHypertension

RRR RRR (%)(%)PerindoprilPerindoprilbetterbetter

PlaceboPlacebobetterbetter

No hypertensionNo hypertension

Diabetes mellitusDiabetes mellitus

No diabetes mellitusNo diabetes mellitus

Stroke/TIAStroke/TIA

No stroke/TIANo stroke/TIA

18.618.6

19.919.9

18.918.9

19.019.0

15.815.8

19.919.9

92% patients on platelet inhibitors92% patients on platelet inhibitors

Sub-groups analysisSub-groups analysis

RRR RRR (%)(%)

Lipid lowering drugLipid lowering drug

PerindoprilPerindoprilbetterbetter

PlaceboPlacebobetterbetter

0.50.5 1.01.0 2.02.0

No lipid lowering drugNo lipid lowering drug

-blockers-blockers

No No -blockers-blockers

Calcium blockersCalcium blockers

No calcium blockersNo calcium blockers

16.316.3

22.322.3

26.426.4

7.07.0

15.815.8

22.222.2

Secondary endpointsSecondary endpoints

Fatal & non fatal MI, unstable anginaFatal & non fatal MI, unstable angina

0.50.5 1.01.0 2.02.0

Perindopril betterPerindopril better Placebo betterPlacebo better

Total mortality, MI, UAP,CATotal mortality, MI, UAP,CA

CV mortality & MICV mortality & MI

CV mortality, MI & strokeCV mortality, MI & stroke

CV mortality, MI, revascularisationCV mortality, MI, revascularisation

CV mortality, MI, unstable anginaCV mortality, MI, unstable angina

Non fatal and fatal MINon fatal and fatal MI

Total mortalityTotal mortality

CV mortalityCV mortality

Unstable anginaUnstable angina

Cardiac arrest Cardiac arrest

StrokeStroke

RevascularisationRevascularisation

Heart failureHeart failure

RRR RRR (%)(%)

14.014.0

19.319.3

17.417.4

11.311.3

15.515.5

16.516.5

23.923.9

11.011.0

13.913.9

7.17.1

45.645.6

4.34.3

4.24.2

39.239.2

Fatal and non fatal MIFatal and non fatal MI

PerindoprilPerindopril

PlaceboPlacebo

00

22

44

66

88

1010

00 11 22 33 44 55 YearsYears

(%)(%)

p < 0.001p < 0.001RRR: 24%RRR: 24%

Hospitalisation for heart failureHospitalisation for heart failure

Perindopril Perindopril

PlaceboPlacebo

5500 11 22 33 44 YearsYears

p = 0.002p = 0.002RRR: 39%RRR: 39%

0.00.0

0.50.5

1.01.0

1.51.5

2.02.0(%)(%)

-1-1 -1/2-1/2 00 33 66 1212 1818 2424 3030 3636 4242 4848 5454 6060

MonthsMonths

7070

8080

9090

100100

110110

120120

130130

140140

mmHgmmHg

Blood pressureBlood pressure

SBP: 5 mmHgSBP: 5 mmHgDBP: 2 mmHgDBP: 2 mmHg

Perindopril Perindopril 8mg8mg PlaceboPlacebo

Adherence to treatmentAdherence to treatment

0 6 12 18 24 30 36

MonthsMonths

0

20

40

60

80

100

120(%)

PlaceboPlacebo

Perindopril Perindopril 8mg8mg

Withdrawal from treatmentWithdrawal from treatment

PerindoprilPerindopril

%%

PlaceboPlacebo

%%

CoughCough 2.72.7 0.50.5

HypotensionHypotension 1.01.0 0.30.3

Kidney failureKidney failure 0.30.3 0.30.3

IntoleranceIntolerance 2.42.4 1.31.3

Study end-pointStudy end-point 6.26.2 7.57.5

HypertensionHypertension 0.40.4 0.80.8

Refuse to continueRefuse to continue 4.34.3 4.24.2

Other reasonOther reason 5.75.7 5.85.8