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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%
COMPASS: critères d’inclusion
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
COMPASS: Ce qui pourrait changer ma pratique
• Il y a un besoin clinique • Réduction de la mortalité
COMPASS: Ce qui pourrait changer ma pratique
• 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 changer ma pratique
COMPASS: Ce qui pourrait ne pas changer ma pratique
• Compétition avec d’autres stratégies…
COMPASS: Ce qui pourrait ne pas changer ma pratique
• Compétition avec d’autres stratégies
• Chez quels patients en pratique?
COMPASS: Ce qui pourrait ne pas changer ma pratique
• Compétition avec d’autres stratégies
• Chez quels patients en pratique?
• Comment sélectionner les patients?
COMPASS: Ce qui pourrait ne pas changer ma pratique
• Compétition avec d’autres stratégies
• Chez quels patients en pratique?
• Comment sélectionner les patients?
• Quelle stratégie d’initiation?
COMPASS: Ce qui pourrait ne pas changer ma pratique
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
Favours Aspirin alone
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
Favours Aspirin alone
*Crude incidence over mean follow-up of 23 monthss
COMPASS: critères d’inclusion
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 - …….
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