Triple thérapie anti-thrombotique

chez le coronarien

Y Cottin

Dijon

« Dans la vie, rien n’est à craindre,

tout est à comprendre »

Marie Curie

Epidémiologie

Aspirine/Clopidogrel/Ticagrelor/Prasugrel

Durée ?

Atrial fibrillation and acute myocardial infarction:

antithrombotic therapy and outcomes

Lopes RN, et al. Am J Med. 2012;125:897-905.

3.9%

9.2%

MI 0.72%/an (D 110) 0.9%/an(R) 0.53%/an (A)

0.74%/an (D 150)

0.53%/an (W) 1.1%/an (W) 0.51%/an (W)

Prognostic Impact of Types of Atrial

Fibrillation in Acute Coronary Syndromes

Lau DH et al. Am J Cardiol. 2009;104:1317-1323.

Death

Prognostic Impact of Types of Atrial

Fibrillation in Acute Coronary Syndromes

Lau DH et al. Am J Cardiol. 2009;104:1317-1323.

Death, MI, stroke

Triple Therapy With Aspirin, Prasugrel, and Vitamin K

Antagonists in Patients With Drug-Eluting Stent

Implantation and an Indication for Oral Anticoagulation

Sarafoff N, et al. JACC. 2013;61:2060-2066.

Triple Therapy With Aspirin, Prasugrel, and Vitamin K

Antagonists in Patients With Drug-Eluting Stent

Implantation and an Indication for Oral Anticoagulation

Sarafoff N, et al. JACC. 2013;61:2060-2066.

Triple Therapy With Aspirin, Prasugrel, and Vitamin K

Antagonists in Patients With Drug-Eluting Stent

Implantation and an Indication for Oral Anticoagulation

Sarafoff N, et al. JACC. 2013;61:2060-2066.

Triple Therapy With Aspirin, Prasugrel, and Vitamin K

Antagonists in Patients With Drug-Eluting Stent

Implantation and an Indication for Oral Anticoagulation

Sarafoff N, et al. JACC. 2013;61:2060-2066.

Concomitant use of warfarin and ticagrelor as an alternative to

triple antithrombotic therapy after an acute coronary syndrome

Braun OO, et al. Thrombosis Reseach. 2015;135:26-30.

Warfarin and ticagrelor

Concomitant use of warfarin and ticagrelor as an alternative to

triple antithrombotic therapy after an acute coronary syndrome

Braun OO, et al. Thrombosis Reseach. 2015;135:26-30.

Warfarin and ticagrelor

Concomitant use of warfarin and ticagrelor as an alternative to

triple antithrombotic therapy after an acute coronary syndrome

Braun OO, et al. Thrombosis Reseach. 2015;135:26-30.

Warfarin and ticagrelor

Madame X, 80 ans, FA depuis 20 ans, ATCD AIT, embolie

MIG, STEMI …, INR 1.9

AVK NACO

Thrombolyse ou PCI

Abord radial

Dose Charge anti-aggrégants

:

- oui/non

- Si oui lesquels ?

HNF

Protection gastrique

Bitherapie ou tritherapie

Durée

Long Terme

Management of acute coronary syndrome in

patients with non-valvular atrial fibrillation: results

of the EuropeanHeart Rhythm Association Survey

Potpara TS, et al. Europace. 2014;16:293–298

Dewilde WJ, et al. Lancet. 2013;381:1107-1115.

Cumulative incidence of the secondary endpoint (death, myocardial

infarction, stroke, target-vessel revascularisation, and stent thrombosis)

WOEST study investigators

Dewilde WJ, et al. Lancet. 2013;381:1107-1115.

Incidence of the primary endpoint (any bleeding)

AVK NACO

Thrombolyse ou PCI

Oui Oui

Abord radial Oui Oui

Dose Charge anti-aggrégants

:

- oui/non

- Si oui lesquels ?

Oui Clopidogrel

Oui Clopidogrel

HNF INR < 2 Relai HNF puis

AVK ?

Protection gastrique Oui Oui

Bitherapie ou tritherapie Type stent Type stent

Durée

Long Terme

Madame X, 80 ans, FA depuis 20 ans, ATCD AIT, embolie

MIG, STEMI …, INR 1.9

Radiale, Thrombectomie, stent

Que faite vous après ?

• AVK ou ADO ? • Risque saignement

• Risque ré-IDM

• Impact de l’âge

• Traitements associés

• Aspirine oui/non

• Protection gastrique

Capodanno d, et al. Circ Cardiovasc Interv. 2014;7:113-24

Antiplatelet Therapy for Stable Coronary Artery

Disease in atrial Fibrillation Patients Taking an Oral

Anticoagulant

A Nationwide Cohort Study

Lamberts M, et al. Circulation. 2014;129:1577-1585

Antiplatelet Therapy for Stable Coronary Artery Disease in

atrial Fibrillation Patients Taking an Oral Anticoagulant

A Nationwide Cohort Study

Lamberts M, et al. Circulation. 2014;129:1577-1585

Antiplatelet Therapy for Stable Coronary Artery Disease in

atrial Fibrillation Patients Taking an Oral Anticoagulant

A Nationwide Cohort Study

Lamberts M, et al. Circulation. 2014;129:1577-1585

Major Bleeding

Antiplatelet Therapy for Stable Coronary Artery Disease in

atrial Fibrillation Patients Taking an Oral Anticoagulant

A Nationwide Cohort Study

Lamberts M, et al. Circulation. 2014;129:1577-1585

All cause of death

Schulman et al. Thromb Haemost 2014;111:575-82

AOD ou AVK

Apixaban versus Warfarin in Patients with Atrial

Fibrillation

Granger CB, et al. N Engl J Med,. 2011; 365: 981-92

MajorBleeding

Primary Efficacy

A randomized, 2-period, crossover design study to

assess the effects of dexlansoprazole, lansoprazole,

esomeprazole, and omeprazole on the steady-state

pharmacokinetics and pharmacodynamics of

clopidogrel in healthy volunteers

Frelinger AL, et al. J AM Coll Cardiol. 2012;59:1304-1311.

Madame X, 80 ans, FA depuis 20 ans, ATCD AIT, embolie

MIG, STEMI …, INR 1.9

Radiale, Thrombectomie, stent,

Apixaban, aspirine, clopidogrel, pantoprazole

Combination of OAC plus single antiplatelet therapy

(preferably clopidogrel 75 mg/day, or as an alternative, aspirin

75–100 mg/day) may be sometimes continued in very

selected cases, e.g. stenting of the left main, proximal left

anterior descending, proximal bifurcation, recurrent MIs, etc.

(Class IIb, level of evidence B).

RE-DUAL PCI: combination therapy in AF pts undergoing PCI

*Warfarin arm: 1 month after bare metal stent or 3 months after drug-eluting stent

ASA, acetylsalicylic acid; PCI, percutaneous coronary intervention

Adapted from Cannon C. AHA 2013 and Boehringer Ingelheim data on file

Dual primary endpoints: death, MI, stroke/SE, and major bleeding

Patients with NVAF

undergoing PCI (n=8520)

R

Dabigatran 150 mg BID

+ P2Y12 inhibitor

Screening

0–72 hours

after PCI

Dabigatran 110 mg BID

+ P2Y12 inhibitor

Warfarin (INR 2.0–3.0)

+ P2Y12 inhibitor + ASA*

n=2840 patients per arm

Minimum treatment duration: 6 months

Population: Diagnosis of ACS

180 – 360 days

treatment 30-day

follow-up R

Index hospitalization: 1. Acute treatment: invasive or medical management 2. Maintenance dose ASA and P2Y12 inhibitor (clopidogrel, ticagrelor)

Ticagrelor + ASA

SOC

SOC

N=1,500

1:1 N=1,500

Ticagrelor + Rivaroxaban 2.5 mg BID

180 – 360 days

treatment

30-day

follow-up R

Clopidogrel + ASA

SOC

SOC 1:1

Clopidogrel + Rivaroxaban 2.5 mg BID

≤ 24h

Clopidogrel

+ ASA

Ticagrelor

+ ASA

GEMINI ACS 1

ACS study with single vs. dual APs

Short design: Multicentre, prospective,

randomized, double-blind, double-dummy,

active-controlled, parallel-group study

Indication: ACS Start: Q1 2015 LPLV: Q1 2017

www.clinicaltrials.gov/ct2/show/NCT02293395

Objective: Safety of Rivaroxaban in addition to either Clopidogrel or Ticagrelor in ACS

Rivaroxaban Use in Patients With AF Undergoing PCI: PIONEER AF-PCI

• Primary endpoint: TIMI major, minor, and bleeding requiring medical attention

• Secondary endpoint: CV death, MI, stroke, and stent thrombosis

Rivaroxaban dosed at 10 mg once daily in patients with CrCl of 30 to <50 mL/min. †Alternative P2Y12 inhibitors: 10 mg once-daily prasugrel or 90 mg twice-daily ticagrelor.

‡Low-dose aspirin (75-100 mg/d).

2100 patients with NVAF

No prior stroke/TIA

PCI with stent placement

R A N D O M I Z E

1,6, or 12 months

Rivaroxaban15 mg qd* Clopidogrel 75 mg qd†

Rivaroxaban 15mg qd Aspirin 75-100 mg qd

Rivaroxaban 2.5 mg bid Clopidogrel 75 mg qd†

Aspirin 75-100 mg qd‡

VKA (target INR 2.0-3.0) Aspirin 75-100 mg qd

VKA (target INR 2.0-3.0) Clopidogrel 75 mg qd†

Aspirin 75-100 mg qd

≤72

hours

After Sheath removal

1,6, or 12 months

End of treatment at

12 months

AF + ACS/PCI Study

► Randomizations to:

1. Apixaban or a VKA (INR 2.0–

3.0)

2. With or without ASA (all

patients get a P2Y12

antagonist)

OAC P2Y12 including ticagrelor / prasugrel

ASA No ASA

Apixaban 5mg BID 5 mg BID

VKA

therapy

INR 2.0–3.0 INR 2.0–3.0

Academic Research Organization:

Duke Clinical Research Institute (DCRI)

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