COMPASS: ce qui pourrait changer ma pratique Gregory Ducrocq - - PowerPoint PPT Presentation

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COMPASS: ce qui pourrait changer ma pratique Gregory Ducrocq - - PowerPoint PPT Presentation

Feb 03, 2023 259 likes •653 views

COMPASS: ce qui pourrait changer ma pratique Gregory Ducrocq DHU-FIRE, Hpital Bichat, Assistance Publique Hpitaux de Paris, INSERM U1148 LVTS, French Alliance for Cardiovascular Clinical Trials Conflits dintrt Orateur: Astra

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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

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

Conflits d’intérêt

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Evolution de la mortalité hospitalières après IDM

Puymirat et al. JAMA 2012

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

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

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

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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

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Comment améliorer le traitement antithrombotique en prévention secondaire? Anticoagulant

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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

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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%

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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

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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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COMPASS: caractéristiques de la population

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

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COMPASS: saignements

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COMPASS: bénéfice clinique net

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COMPASS: Ce qui pourrait changer ma pratique

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  • Il y a un besoin clinique

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

COMPASS: Ce qui pourrait changer ma pratique

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

COMPASS: Ce qui pourrait changer ma pratique

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

représente une large proportion de nos patients

Exclude d 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

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COMPASS: Ce qui pourrait ne pas changer ma pratique

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  • Compétition avec d’autres

stratégies…

COMPASS: Ce qui pourrait ne pas changer ma pratique

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  • Compétition avec d’autres

stratégies

  • Chez quels patients en

pratique?

COMPASS: Ce qui pourrait ne pas changer ma pratique

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  • Compétition avec d’autres

stratégies

  • Chez quels patients en

pratique?

  • Comment sélectionner les

patients?

COMPASS: Ce qui pourrait ne pas changer ma pratique

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  • 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

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Conclusion

  • Nouveau concept en

prévention secondaire

  • Beaucoup de

questions sur la mise en pratique

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Backup

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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;
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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)

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Eligibility to COMPASS and reasons for exclusion

Excluded 29,9% Non- included 17,2%

Eligible 52,9%

10 20 30 40 50 60 51,8 44,8 25,9 12,4 2,2

High Bleeding Risk Oral Anticoagulant Treatment DAPT for ACS/PCI < 12 months Ischaemic stroke < 1 year Severe renal failure

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

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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

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

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 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

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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

COMPASS Trial Details

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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

COMPASS Result Details

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

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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

COMPASS Result Details

Favours Riva 2.5mg BID + Aspirin Favours Aspirin alone Eikelboom JW et al. New Engl J Med 2017; DOI: 10.1056/NEJMoa1709118

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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 10 Favours Riva 2.5mg BID + Aspirin Favours Aspirin alone

*Crude incidence over mean follow-up of 23 monthss

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COMPASS: critères d’inclusion

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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

  • …….