K Fox, W Remme, C Daly, M Bertrand, R Ferrari, M SimoonsK Fox, W Remme, C Daly, M Bertrand, R Ferrari, M Simoons

On behalf of the EUROPA investigators.On behalf of the EUROPA investigators.

The diabetic sub study ofThe diabetic sub study of

ACE inhibitor therapy of proven benefit in ACE inhibitor therapy of proven benefit in secondary prevention in myocardial infarction secondary prevention in myocardial infarction and heart failureand heart failure

EUROPA concluded that perindopril was also EUROPA concluded that perindopril was also beneficial in patients with CAD, without heart beneficial in patients with CAD, without heart failure and with broad range of riskfailure and with broad range of risk

Within the coronary disease population, Within the coronary disease population, diabetics are a subpopulation at high riskdiabetics are a subpopulation at high risk

BackgroundBackground

Aim of the studyAim of the study

To investigate the effect of the ACE To investigate the effect of the ACE inhibitorinhibitor

perindopril 8 mg once dailyperindopril 8 mg once daily added to standard therapy added to standard therapy

on cardiovascular eventson cardiovascular events

in diabetic patientsin diabetic patients

with documented coronary diseasewith documented coronary disease

Study endpointsStudy endpoints

CV mortality + non fatal MI + cardiac arrestCV mortality + non fatal MI + cardiac arrest

Fatal and non-fatal MIFatal and non-fatal MI Non-fatal MINon-fatal MI StrokeStroke Hospitalisation for heart failureHospitalisation for heart failure Development of renal failureDevelopment of renal failure

Primary endpointPrimary endpoint

Secondary endpointsSecondary endpoints

Patient populationPatient 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 characteristicsBaseline characteristics

EUROPAEUROPA PERSUADE PERSUADE n=1502n=1502

PlaceboPlacebo(mean (mean ±± SD) SD)

PerindoprilPerindopril(mean (mean ±± SD) SD)(mean (mean ±± SD) SD)

Age Age (yrs)(yrs) 62 62 ±± 9 962 62 ±± 9 960 60 ±± 9 9

Male Male (%)(%) 818183838585

Weight Weight (kg)(kg) 82 82 ±± 13 1383 83 ±± 13 1381 81 ±± 12 12

SBP SBP (mmHg)(mmHg) 140 140 ±± 16 16140 140 ±± 15 15137 137 ±± 15 15

DBP DBP (mmHg)(mmHg) 82 82 ±± 8 881 81 ±± 8 882 82 ±± 8 8

Medical history & risksMedical history & risks

EUROPAEUROPA PERSUADE PERSUADE n=1502n=1502

PlaceboPlacebo(%)(%)

PerindoprilPerindopril(%)(%)(%)(%)

MIMI 686865656565

CABGCABG 333330303232

PCIPCI 262627272929

Stroke / TIAStroke / TIA 556633

PVDPVD 1212141477

HypertensionHypertension 414138382727

HyperlipidemiaHyperlipidemia 616161616363

Clinical outcomeClinical outcome

00

22

44

66

88

1010

1212

1414

161614.1

8.9

PrimaryPrimaryEndpointEndpoint

11.1

6.5

TotalTotalMortalityMortality

7.1

3.8

CVCVMortalityMortality

8.9

6.0

MIMI

2.71.6

StrokeStroke

2.51.3

HeartHeartFailureFailure

1.0 0.6

Doubl.Doubl.CreatinineCreatinine

PERSUADEPERSUADE EUROPAEUROPA

(%)(%)

RRR with perindoprilRRR with perindopril

Primary EndpointPrimary Endpoint

Total MortalityTotal Mortality

CV mortalityCV mortality

All MIAll MI

Non Q MINon Q MI

Heart FailureHeart Failure

StrokeStroke

0.20.2 0.40.4 0.60.6 0.80.8 1.01.0 1.21.2 1.41.4 1.61.6 1.81.8

PerindoprilPerindoprilbetterbetter

PlaceboPlacebobetterbetter

(%) RRR(%) RRR

Primary endpointPrimary endpoint

2020

1616

1212

88

44

0000 11 22 33 44 55

Years from randomisationYears from randomisation

EUROPAEUROPA

placeboplacebo

perindoprilperindopril

placeboplacebo

perindoprilperindoprilPERSUADEPERSUADE

PERSUADE RRR 19%PERSUADE RRR 19%p=0.131p=0.131

% CV death, MI and cardiac arrest% CV death, MI and cardiac arrest

00 11 22 33 44 55

Years from randomisationYears from randomisation

1414

1010

66

44

00

Fatal and non fatal MIFatal and non fatal MI

placeboplacebo

perindoprilperindoprilplaceboplacebo

perindoprilperindopril

EUROPAEUROPA

PERSUADEPERSUADE

PERSUADE RRR 23%PERSUADE RRR 23%p=0.143p=0.143

(%)(%)

Heart Failure Heart Failure

Years from randomisationYears from randomisation

placeboplacebo

perindoprilperindoprilplaceboplacebo

perindoprilperindopril

PERSUADE RRR 46%PERSUADE RRR 46%p=0.06p=0.06

PERSUADEPERSUADE

EUROPAEUROPA

00 11 22 33 44 5500

22

44

(%)(%)

Summary of results Summary of results

In PERSUADE, the In PERSUADE, the relativerelative risk reduction with risk reduction with

perindopril on 1perindopril on 1°° and 2 and 2°° endpoints was similar endpoints was similar

toto

that in the main EUROPA populationthat in the main EUROPA population

Primary endpoint Primary endpoint RRR 19%RRR 19%

Fatal and nonfatal MI Fatal and nonfatal MI RRR 23%RRR 23%

Heart Failure Heart Failure RRR 46%RRR 46%

ConclusionConclusion

Perindopril 8 mg once daily reducesPerindopril 8 mg once daily reduces

cardiovascular eventscardiovascular events

in patients with coronary diseasein patients with coronary disease

and diabetesand diabetes

NNTNNT to prevent one cardiovascular death to prevent one cardiovascular death

or nonfatal myocardial infarction is justor nonfatal myocardial infarction is just

27 27 patients over 4 yearspatients over 4 years