COMPASS: ce qui pourrait changer ma...

COMPASS: ce qui pourrait changer ma pratique

Gregory Ducrocq

DHU-FIRE,

Hôpital Bichat, Assistance Publique – Hôpitaux de Paris,

INSERM U1148 LVTS,

French Alliance for Cardiovascular Clinical Trials

Orateur: Astra Zeneca, Bayer, Biotronik, BMS, Sanofi CEC: Sanofi, Philips DSMB: Abbot, MicroPort Frais de voyage: Astra Zeneca, Biotronik

Conflits d’intérêt

Evolution de la mortalité hospitalières après IDM

Puymirat et al. JAMA 2012

USIK USIC-2000 FAST-MI FAST-MI-2

Long-term death rates post ACS remain high The UK–Belgian GRACE experience

Fox KAA, et al. Eur Heart J 2010;31:2755–2764

Comment améliorer le traitement antithrombotique en prévention secondaire?

Antiagrégants plaquettaires

TRA2P trial Morrow et al NEJM 2012

Inhibiteur du récepteur de la thrombine PAR-1: Vorapaxar

Inhibiteur du récepteur P2Y12: ticagrelor

Pegasus trial Bonaca et al NEJM 2015

Comment améliorer le traitement antithrombotique en prévention secondaire?

Anticoagulant

COMPASS: Design

R

Rivaroxaban 2.5 mg b.i.d + Aspirin 100 mg o.d

Rivaroxaban 5 mg b.i.d

Aspirin 100 mg o.d

Screening period Run-in period

Primary outcome : MI, Stroke, CV death

Eikelboom J.W. et al N Engl J Med, 2017

27 400 patients

COMPASS: critères d’inclusion

Coronariens - ATCD IDM - Multitronculaires

- Symptomatiques - ATL multi-vaisseaux - Pontage multi vaisseaux

Maladie artérielle périphérique - ATCD revascularisation des membres

inférieurs - ATCD amputation - Claudication intermittente et

- ABI < 0.9 - Sténose artère périphérique ≥ 50%

- ATCD de revascularisation carotide ou sténose carotide≥ 50%


Coronariens - ATCD IDM - Multitronculaires

- Symptomatiques - ATL multi-vaisseaux - Pontage multi vaisseaux

Coronariens: critères d’enrichissement - ≥ 65 ans - < 65 ans

- Tabagisme actif - Diabète - Insuffisance rénale (DFG

< 60) - Insuffisance cardiaque - AVC non lacunaire ≥ 1

mois

COMPASS: critères de non-inclusion

- Haut risque de saignement - AVC < 1 mois - ATCD d’AVC hémorragique ou

lacunaire - Insuffisance cardiaque

- FE < 30% - NYHA 3 ou 4

- DFG < 15 mL / min - Indication de DAPT - Maladie non cardiaque au

pronostic défavorable - …….

COMPASS: caractéristiques de la population

COMPASS: critère primaire d’efficacité (IDM, AVC , décès CV)

COMPASS: saignements

COMPASS: bénéfice clinique net

COMPASS: Ce qui pourrait changer ma pratique

• Il y a un besoin clinique

Fox KAA, et al. Eur Heart J 2010;31:2755–2764


• Il y a un besoin clinique • Réduction de la mortalité


• Il y a un besoin clinique • Réduction de la mortalité • La population de COMPASS

représente une large proportion de nos patients

Excluded

29,9%

Non-include

d 17,2%

Eligible 52,9%

Darmon A et al Eur Heart J 2017

Analyse du registre REACH 31 873 patients


COMPASS: Ce qui pourrait ne pas changer ma pratique

• Compétition avec d’autres stratégies…


• Compétition avec d’autres stratégies

• Chez quels patients en pratique?




• Comment sélectionner les patients?




• Comment sélectionner les patients?

• Quelle stratégie d’initiation?


Conclusion

• Nouveau concept en prévention secondaire

• Beaucoup de questions sur la mise en pratique

Backup

Bleedings events

Aspirin n (%)

Riva 2.5mg BID + Aspirin

n (%)

Site of Major Bleeding :

GI 65 (0,7) 140(1,5) 2,15(1,60-2,89) <0,001

Intra cranial 24(0,3) 28(0,3) 1,16(-0,67-2,00) 0,60

Skin or injection site 12(0,1) 28(0,3) 2,31(1,18-4,54) 0,01

Urinary 21(0,2) 13(0,1) 0,61(0,31-1,23) 0,16

1. Eikelboom JW et al. New Engl J Med 2017; DOI: 10.1056/NEJMoa1709118;

Identifying the COMPASS Eligible Subset in the REACH Registry

REACH overall population N=65,531

Excluded: CVD alone or risk factor alone n=21,052

REACH PAD/CAD n=44,479

Excluded: missing data on inclusion criteria AND exclusion criteria n=12,606

REA CH PAD/CAD evaluable = COMPASS-EVALUABLE n=31,873

Excluded: exclusion criteria n=9518

COMPASS-EXCLUDED

Excluded: patients with CAD/PAD but not fulfilling inclusion criteria

n=5480 COMPASS NOT INCLUDED

COMPASS-ELIGIBLE N=16,875

COMPASS INELIGIBLE n=14,998

Darmon A et al Eur Heart J, 2017 (In Press)

Eligibility to COMPASS and reasons for exclusion

Excluded 29,9%

Non-included

17,2%

Eligible 52,9%

0

10

20

30

40

50

60 51,8 44,8

25,9

12,4

2,2

High Bleeding Risk

Oral AnticoagulantTreatmentDAPT for ACS/PCI < 12monthsIschaemic stroke < 1yearSevere renal failure

Darmon A et al Eur Heart J, 2017 (In Press)

2.1

1.1 0.7 0.4

6.5

5.6

3.6

1.9

4.2

3.2

1.9 1.2

2.9 2.2

1.2 1.0

0

1

2

3

4

5

6

7

CV death, MI, or Stroke All cause mortality CV Death Non CV Death

Non Included Excluded Eligible COMPASS aspirin alone

p < 0,01 for each comparison

Main cardiovascular events rates

Per 100 patients / year

Previous MI

OR

Stable angina or unstable angina with

documented multi-vessel CAD, >50% stenosis

in at least 2 major coronary arteries on coronary

angiography, or positive stress test

(electrocardiogram) or nuclear perfusion

scintigram

OR

Multi-vessel percutaneous coronary intervention

OR

Multi-vessel coronary artery bypass grafting

surgery within 1 week or at least 4 years ago or

with recurrent angina or ischaemia at any time

following surgery

Previous aorto-femoral bypass surgery, limb

bypass surgery or percutaneous transluminal

angioplasty of the iliac or infrainguinal arteries

OR

Previous limb or foot amputation for arterial

vascular disease*

OR

History of intermittent claudication and either an

ankle/arm blood pressure ratio ≤0.90 or

significant peripheral artery stenosis (>50%)

documented by angiography or non-invasive

testing by duplex ultrasound

OR

Asymptomatic carotid artery stenosis# >50% as

diagnosed by duplex ultrasound or angiography

COMPASS: Study Population

Definition of CAD Definition of PAD

PAD CAD

COMPASS Randomised 27,395 Patients with

CAD or PAD Worldwide

COMPASS was conducted in 33 countries with 602 sites

www.clinicaltrials.gov/ct2/show/NCT01776424 [accessed 21 Mar 2017]; Bosch J et al, Can J Cardiol 2017;33:1027–1035

Canada

N=2443

United States

N=1475

Colombia N=942

Ecuador N=257 Brazil

N=1515

Chile N=641

Argentina N=2789

South Africa

N=581

UK

N=541

Ireland

N=382

France N=191

Finland

N=119

Netherlands

N=2522

Germany N=766

Switzerland N=58

Italy N=1014

Israel

N=263

Sweden

N=735

Denmark

N=575

Czech Rep

N=1553

Russia

N=682

China

N=1086

Ukraine

N=821

Hungary N=734

Malaysia

N=247

South Korea N=415

Japan N=1556

Philippines N=651

Australia

N=353

Belgium N=455

Poland

N=518

Romania N=423

Slovakia N=92

◄ Index C

OM

PA

SS

Tria

l

Deta

ils

Efficacy of Combination Regimen of Rivaroxaban 2.5 mg BID

with Aspirin was Consistent Across all Subgroups (1 of 2)

Rivaroxaban

2.5 mg bid + aspirin

n/N (%)

Aspirin

n/N (%)

Hazard Ratio (95% CI) Hazard Ratio

(95% CI)

Interaction

p-value

All patients 379/9152 (4.1) 496/9126 (5.4) 0.755 (0.661–0.863)

Age 0.243

<65 years 80/2150 (3.7) 126/2184 (5.8) 0.640 (0.484–0.848)

≥65 to <75 years 179/5078 (3.5) 238/5045 (4.7) 0.743 (0.612–0.901)

≥75 years 120/1924 (6.2) 132/1897 (7.0) 0.880 (0.687–1.127)

Sex 0.759

Male 300/7093 (4.2) 393/7137 (5.5) 0.764 (0.657–0.888)

Female 79/2059 (3.8) 103/1989 (5.2) 0.723 (0.539–0.969)

Region 0.599

North America 63/1304 (4.8) 80/1309 (6.1) 0.766 (0.551–1.065)

South America 93/2054 (4.5) 111/2054 (5.4) 0.823 (0.644–1.052)

West Europe 117/2855 (4.1) 141/2855 (4.9) 0.657 (0.474–0.910)

East Europe 59/1607 (3.7) 90/1604 (5.6) 0.620 (0.430–0.894)

Asia Pacific & Other 47/1332 (3.5) 74/1304 (5.7) 0.834 (0.632–1.100)

Ethnicity 0.375

White Caucasian 236/5672 (4.2) 307/5682 (5.4) 0.761 (0.642–0.901)

Black/African American 2/76 (2.6) 8/92 (8.7) 0.305 (0.064–1.460)

Asian 54/1452 (3.7) 81/1397 (5.8) 0.638 (0.452–0.901)

Other 87/1952 (4.5) 100/1955 (5.1) 0.869 (0.652–1.159) 0,1 1 10

◄ Index

Favours Riva 2.5mg BID

+ Aspirin

Favours Aspirin alone

CO

MP

AS

S R

esu

lt

Deta

ils

Eikelboom JW et al. New Engl J Med 2017; DOI: 10.1056/NEJMoa1709118

Rivaroxaban

2.5 mg bid + aspirin

n/N (%)

Aspirin

n/N (%)

Hazard Ratio (95% CI) Hazard Ratio

(95% CI)

Interaction

p-value

Body weight 0.640

≤60 kg 41/903 (4.5) 45/837 (5.4) 0.831 (0.544–1.270)

>60 kg 335/8239 (4.1) 448/8284 (5.4) 0.746 (0.648–0.859)

eGFR 0.920

>60 mL/min 134/2048 (6.5) 180/2109 (8.5) 0.749 (0.599–0.937)

≤60 mL/min 245/7100 (3.5) 316/7016 (4.5) 0.762 (0.645–0.900)

Baseline tobacco use 0.333

Yes 81/1944 (4.2) 122/1972 (6.2) 0.672 (0.507–0.890)

No 298/7208 (4.1) 374/7154 (5.2) 0.783 (0.673–0.912)

Baseline diabetes 0.726

Yes 179/3448 (5.2) 240/3474 (6.9) 0.737 (0.607–0.894)

No 200/5704 (3.5) 256/5652 (4.5) 0.773 (0.642–0.930)

History of hypertension 0.594

Yes 318/6904 (4.6) 409/6877 (5.9) 0.767 (0.663–0.880)

No 61/2248 (2.7) 87/2249 (3.9) 0.693 (0.500–0.962)

Baseline dyslipidaemia 0.401

Yes 324/8238 (3.9) 428/8156 (5.2) 0.741 (0.642–0.856)

No 55/914 (6.0) 68/970 (7.0) 0.870 (0.610–1.242)

0,1 1 10

Efficacy of Combination Regimen of Rivaroxaban 2.5 mg BID

with Aspirin was Consistent Across all Subgroups (2 of 2)

◄ Index C

OM

PA

SS

Resu

lt

Deta

ils

Favours Riva 2.5mg BID

+ Aspirin


Eikelboom JW et al. New Engl J Med 2017; DOI: 10.1056/NEJMoa1709118

COMPASS: critère primaire d’efficacité

Primary efficacy:

MACE*

Aspirin

n (%)

Riva 2.5mg BID

+ Aspirin

n (%)

HR HR (95% CI) p-value RRR

MI, stroke or CV death

Overall CAD/PAD 496 (5.4) 379 (4.1) 0.76 <0.001 -24%

Stroke 142 (1.6) 83 (0.9) 0.58 <0.001 -42%

CV death 203 (2.2) 160 (1.7) 0.78 0.02 -22%

MI 205 (2.2) 178 (1.9) 0.86 0.14 -14%NS

CAD 460 (5.6) 347 (4.2) 0.74 <0.0001 -26%

PAD 174 (6.9) 126 (5.1) 0.72 <0.005 -28%

0,1 1 10Favours Riva 2.5mg BID

+ Aspirin


*Crude incidence over mean follow-up of 23 monthss

COMPASS: critères de non-inclusion

- Haut risque de saignement - AVC < 1 mois - ATCD d’AVC hémorragique ou

lacunaire - Insuffisance cardiaque

- FE < 30% - NYHA 3 ou 4

- DFG < 15 mL / min - Indication de DAPT - Maladie non cardiaque au

pronostic défavorable - …….

COMPASS: ce qui pourrait changer ma...

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