Preliminary Results

A Multicenter Randomized Trial ofA Multicenter Randomized Trial of Immediate Versus Delayed Invasive StrategyImmediate Versus Delayed Invasive Strategy

in Patients with Non-ST Elevation ACSin Patients with Non-ST Elevation ACS

Angioplasty to Blunt the rise Of troponinin Acute coronary syndromes Randomized for an immediate or Delayed intervention

Funded by the Programme Hospitalier de Recherche Clinique (French Ministry of Health)Funded by the Programme Hospitalier de Recherche Clinique (French Ministry of Health)Sponsored by Assistance Publique-Hopitaux de Paris (AP-HP)Sponsored by Assistance Publique-Hopitaux de Paris (AP-HP)Led by the A.C.T.I.O.N. group (Academic Research Organization)Led by the A.C.T.I.O.N. group (Academic Research Organization)Coordinating Center: Pitié-Salpêtrière University HospitalCoordinating Center: Pitié-Salpêtrière University HospitalData Management and Statistics: URC Lariboisière University HospitalData Management and Statistics: URC Lariboisière University HospitalAdditional support from Eli-LillyAdditional support from Eli-Lilly

G. Montalescot, on behalf of the ABOARD investigators

G. Montalescot, disclosure: research grant, consulting or speaker fee from BMS, Boston scientific, Cordis, Daiichi Sankyo, Eli Lilly, GSK, SAG, MSD, The Medicines Company, Medtronic, Novartis, Portola, Schering.

Preliminary Results

BackgroundBackgroundBackgroundBackground

Randomized trials have demonstrated that an Randomized trials have demonstrated that an

invasive strategy is superior to a conservative invasive strategy is superior to a conservative

strategy in NSTE-ACSstrategy in NSTE-ACS

The optimal timing of intervention remains a The optimal timing of intervention remains a

matter of debatematter of debate

A “primary PCI” approach of NSTE-ACS has A “primary PCI” approach of NSTE-ACS has

not been tested yetnot been tested yet

Preliminary Results

Time to catheterization (hrs)Time to catheterization (hrs)Time to catheterization (hrs)Time to catheterization (hrs)

EARLYEARLY LATELATE

FRISC 2 (1999) 96 408

TRUCS (2000) 48 120

TIMI-18 (2001) 22 79

VINO (2002) 6 1464

RITA 3 (2002) 48 1020

ELISA (2003) 6 50

ISAR-COOL (2003) 3 86

ICTUS (2005) 23 283

TIME-ACS (2008) 14 50

ABOARD (2009) Immediate Next morning

Preliminary Results

Study objectiveStudy objectiveStudy objectiveStudy objective

To determine whether immediate To determine whether immediate

intervention (“primary PCI strategy”) is intervention (“primary PCI strategy”) is

superior to delayed intervention (“next day superior to delayed intervention (“next day

strategy”) in patients with moderate-to-high strategy”) in patients with moderate-to-high

risk (TIMI score risk (TIMI score >> 3) non-ST segment 3) non-ST segment

elevation ACS.elevation ACS.

Preliminary Results

ABOARD study designABOARD study designABOARD study designABOARD study design

NSTE-ACS NSTE-ACS 2 of 3 Criteria: Ischemic symptom, ST-T change, troponin rise2 of 3 Criteria: Ischemic symptom, ST-T change, troponin rise

with TIMI score with TIMI score >> 3 3

Immediate cathImmediate cath Next day cathNext day cath

All PCIs on abciximabAll PCIs on abciximab

1-month Follow-up1-month Follow-up

IVRS RANDOMIZATIONIVRS RANDOMIZATION

Preliminary Results

Troponin during hospitalizationTroponin during hospitalizationTroponin during hospitalizationTroponin during hospitalization

« The preferred biomarker for myocardial necrosis is cardiac troponin »

20072007

ACSACS

PCIPCI1.35 (1.13-1.60)ALLAntman EM et al – NEJM 1996

Nienhuis MB et al - CCI 2008

Preliminary Results

OutcomesOutcomesOutcomesOutcomes

Primary Primary

− MI: defined as the peak of troponin I during MI: defined as the peak of troponin I during hodpitalizationhodpitalization

SecondarySecondary

1.1. Death (any), new MI (CK-MB) or urgent Death (any), new MI (CK-MB) or urgent revascularization (PCI or CABG)revascularization (PCI or CABG)

2.2. Death, new MI, urgent revascularization or Death, new MI, urgent revascularization or recurrent ischemia recurrent ischemia

3.3. Individual parametersIndividual parameters

Preliminary Results

Statistical AnalysisStatistical AnalysisStatistical AnalysisStatistical Analysis

Study Power:Study Power: 352 patients: 80% power to 352 patients: 80% power to detect an effect size equal to 0.3detect an effect size equal to 0.3

Randomization:Randomization: Central 24 hour IVRS Central 24 hour IVRS

Analysis:Analysis: Intention to treat; Tests: Mann- Intention to treat; Tests: Mann-Whitney test for non-gaussian quantitative Whitney test for non-gaussian quantitative parameters, Chi-square or Fisher’s exact parameters, Chi-square or Fisher’s exact probability tests for qualitative parameters .probability tests for qualitative parameters .

Follow-up:Follow-up: 100% 100%

Den

sity

Den

sity

TroponinTroponin levelslevels

Den

sity

Den

sity

TroponinTroponin levelslevels

Den

sity

Den

sity

TroponinTroponin levelslevels

Preliminary Results

Top-10 Recruiting CentersTop-10 Recruiting CentersTop-10 Recruiting CentersTop-10 Recruiting Centers

1- G. Montalescot – 1- G. Montalescot – Pitié, ParisPitié, Paris

2- G. Cayla – 2- G. Cayla – NimesNimes

3- S. Elhadad – 3- S. Elhadad – LagnyLagny

4- H. Lebreton – 4- H. Lebreton – RennesRennes

5- F. Leclercq 5- F. Leclercq –– Montpellier Montpellier

6- F. Duclos – 6- F. Duclos – ArgenteuilArgenteuil

7- J.L. Dubois-Randé – 7- J.L. Dubois-Randé – CréteilCréteil

8- P.G. Steg – 8- P.G. Steg – Bichat,Bichat, ParisParis

9- L. Payot – 9- L. Payot – MontreuilMontreuil

10- P. Henry – 10- P. Henry – Lariboisière,Lariboisière, ParisParis

Preliminary Results

Baseline CharacteristicsBaseline CharacteristicsBaseline CharacteristicsBaseline Characteristics

Characteristic Immediate(N=175)

Delayed(N=177)

Age, mean ± sd, y 65 ± 12 65± 12

Female sex, % 27.4 29.4

Weight, mean ± sd, kg 77 ± 16 76 ± 15

Current smoking, % 32.0 33.9

Diabetes mellitus, % 21.7 32.2

Previous CABG, % 5.1 6.8

Previous MI, % 16.6 18.6

Previous PCI, % 24.6 30.5

Previous Stroke, % 5.2 4.5

Cardiac Insufficiency, % 4.0 4.0

Preliminary Results

Index ACS eventIndex ACS eventIndex ACS eventIndex ACS event

Entry criteria, (%) Immediate(N=175)

Delayed(N=177)

Ischemic symptom 98.2 97.7

ST-T segment changes 69.7 76.8

Elevated Troponin I 75.4 72.9

TIMI score, (%)

> 3 95.4 95.5

> 5 22.9 30.5

Preliminary Results

In-hospital medicationsIn-hospital medicationsIn-hospital medicationsIn-hospital medications

Immediate(N=175)

Delayed(N=177)

Aspirin, (%) 99.4 100

Clopidogrel, (%) 96.6 98.9

Loading dose, mean ± sd, mg 660 ± 268 663 ± 267

Maintenance dose, mean ± sd, mg 111 ± 40 111 ± 39

Abciximab, (%) 65.1 57.4

Unfractionated heparin only, (%) 5.1 3.4

Low Molecular Weight Heparin only, (%) 68.6 67.2

Both UFH and LMWH, (%) 22.9 28.8

Neither UFH nor LMWH, (%) 2.9 0.6

Beta-blocker, (%) 87.4 85.3

Statin, (%) 94.3 95.5

ACE inhibitor or ARB, (%) 84.5 80.2

Preliminary Results

Time to catheterization (hrs)Time to catheterization (hrs)Time to catheterization (hrs)Time to catheterization (hrs)

IMMEDIATEIMMEDIATE DELAYEDDELAYED

FRISC 2 (1999) 96 408

TRUCS (2000) 48 120

TIMI-18 (2001) 22 79

VINO (2002) 6 1464

RITA 3 (2002) 48 1020

ELISA (2003) 6 50

ISAR-COOL (2003) 3 86

ICTUS (2005) 23 283

TIME-ACS (2008) 14 50

ABOARD (2009)median (IQR), hr.min

1.10(0.51-2.03)

20.48(17.30-24.36)

Preliminary Results

InterventionsInterventionsInterventionsInterventionsIMMEDIATEIMMEDIATE DELAYEDDELAYED

Radial access (%) 87.487.4 81.881.8

Culprit artery

Left main trunk, (%) 4.1 7.3

Left anterior descending artery, (%) 48.6 45.0

Circumflex artery, (%) 24.7 29.1

Right coronary artery, (%) 24.7 25.2

Coronary bypass graft, (%) 2.1 2.0

Percutaneous Coronary Intervention, (%) 80.1 69.5

Stent (at least one), (% of PCI) 94.0 96.2

DES (at least one), (% of PCI) 47.9 55.2

Number of stents/patient, mean±sd 1.2 ± 0.9 1.2 ± 1.0

CABG surgery, (%) 11.0 11.3

Preliminary Results

Primary EP (peak of troponin I)Primary EP (peak of troponin I)Primary EP (peak of troponin I)Primary EP (peak of troponin I)

0 20 40 60 80 100

0.0

00

.02

0.0

40

.06

0.0

80

.10

0.1

20

.14

Troponin I (ng/mL)

De

nsity

Distribution curves of the peaks values of troponin in the immediate and delayed groups

immediate groupdelayed group

Median, IQR

2.1 (0.3-7.1)1.7 (0.3-7.2)

Peak values of troponin I in the 2 groups

p = 0.70

Preliminary Results

Composite Ischemic Endpoints at 1 monthComposite Ischemic Endpoints at 1 month

%%

0

5

10

15

20

25

Death / MI / UR Death / MI / UR / RI

Immediate

Delayed

Key secondary EP

P=0.31

P=0.94

Preliminary Results

Individual Ischemic Endpoints at 1 monthIndividual Ischemic Endpoints at 1 month

02468

101214161820

ImmediateDelayed

%%

P=0.28

P=0.09

P=0.32

P=0.57

P=0.62

P=0.08

Preliminary Results

Safety outcomes at 1 monthSafety outcomes at 1 monthSafety outcomes at 1 monthSafety outcomes at 1 month

Immediate Delayed PP

Major bleeding at 1 month, (%)Major bleeding at 1 month, (%) 4.0 6.8 0.250.25

Non-CABG related major bleeding, Non-CABG related major bleeding, 2.3 5.1 0.260.26

CABG-related major bleedingCABG-related major bleeding 1.7 1.7 1.001.00

Transfusion Transfusion >> 2 units 2 units 3.4 5.6 0.320.32

Transfusion Transfusion >> 5 units 5 units 1.1 1.1 1.001.00

Thrombocytopenia at 1 month, (%)Thrombocytopenia at 1 month, (%) 2.9 4.5 0.410.41

Non-CABG Non-CABG thrombocytopenia,thrombocytopenia, (%) (%) 2.3 4.0 0.540.54

Post-CABG Post-CABG thrombocytopenia,thrombocytopenia, (%) (%) 0.6 0.6 1.001.00

Preliminary Results

Sites of Major BleedingsSites of Major BleedingsSites of Major BleedingsSites of Major Bleedings

1- Gastro-Intestinal1- Gastro-Intestinal 44

2- Puncture-related2- Puncture-related 44

3- Hemopericardium3- Hemopericardium 22

4- Intracranial4- Intracranial 11

5- Epistaxis5- Epistaxis 11

6- Hematoma (not puncture-related)6- Hematoma (not puncture-related) 11

unknownunknown 77

One patient had 2 bleeding events

n

Preliminary Results

Subgroup analysis (primary EP)Subgroup analysis (primary EP)Subgroup analysis (primary EP)Subgroup analysis (primary EP)

Immediate better Delayed better

Median differences and Hodges-Lehmann CI for the primary end point (peak of troponin)

Preliminary Results

Hospital stayHospital stayHospital stayHospital stay

ImmediateImmediateMedian, IQR, hrsMedian, IQR, hrs

55( 30; 98)

DelayedDelayedMedian, IQR, hrsMedian, IQR, hrs

77( 49; 145)

P<0.001

Preliminary Results

ConclusionsConclusionsConclusionsConclusions

A « primary PCI strategy » in NSTE-ACS (compared A « primary PCI strategy » in NSTE-ACS (compared

with a rapid intervention on the next day):with a rapid intervention on the next day):

− is feasible, but does not reduce the risk of MI (primary is feasible, but does not reduce the risk of MI (primary

outcome)outcome)

− is not associated with significant differences in other efficacy is not associated with significant differences in other efficacy

or safety outcomesor safety outcomes

− does not benefit to a particular subgroup of patientsdoes not benefit to a particular subgroup of patients

− shortens significantly hospital stayshortens significantly hospital stay

Preliminary Results

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