ARCTIC investigators s ARCTIC : A ssessment by a double R - - PowerPoint PPT Presentation

ARCTIC investigators

COI DISCLOSURE FOR DR. MONTALESCOT: Research Grants to the Institution or Consulting/Lecture Fees from Abbott Vascular, Astra-Zeneca, Bayer, Biotronik, Boehringer-Ingelheim, Boston Scientific, Cleveland Clinic Foundation, Cardiovascular Research Foundation, Cordis, Daiichi-Sankyo, Duke institute, Eli-Lilly, Europa, Fédération Française de Cardiologie, Fondation de France, GSK, ICM, INSERM, Medtronic, Menarini, Nanospheres, Novartis, Pfizer, Sanofi-Aventis Group, Servier, Société Française de Cardiologie, The Medicines Company, TIMI group. ARCTIC: Assessment by a double Randomization of a Conventional antiplatelet strategy versus a monitoring-guided strategy for drug-eluting stent implantation and, of Treatment Interruption versus Continuation one year after stenting - NCT 00827411 -

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Embargoed for 3:52pm PT, Sunday, Nov. 4 LBCT01-G. Montalescot - ARCTIC

ACTION Study Group (Academic Research Organization, Paris):

• Academic Coordinating Center: Institute of Cardiology - Pitié-Salpêtrière, Paris
• Academic Sponsor: AP-HP, Paris
• Academic Global Trial Operations: URC - Lariboisière, Paris
• Funding: ACTION, Fondation de France, Fondation SGAM, Sanofi-Aventis,

Cordis, Boston-Scientific, Medtronic

• Steering Committee: G. Montalescot, JP Collet, G. Cayla, T. Cuisset, S. Elhadad,
• G. Rangé, E. Vicaut
• Investigation sites : 38 French Intervention Centers

Trial conduct

CHU Pitié-Salpêtrière, Paris, Drs Montalescot/Collet Hôpital de la Timone, Marseille, Dr Cuisset CH de Chartres, Dr Rangé CHU Carémeau, Nîmes, Drs Ledermann/Cayla CH de Lagny, Marne-la-Vallée, Drs Elhadad/Cohen Clinique Sainte Clothilde, La Réunion, Dr Pouillot CH Clermont-Ferrand, Dr Motreff Hôpital Lariboisière, Paris, Dr Henry Hôpital de Rangueil, Toulouse, Dr Carrié CH de la Région Annecienne, Annecy, Dr Belle CH de Bastia, Dr Boueri Hôpital Cardiologique Albert Calmette, Lille, Dr Van Belle GH du Centre Alsace, Drs Lhoest/Levai Hôpital Nord Marseille, Dr Paganelli CHU Jean Minjoz, Besançon, Dr Bassand Clinique du Parc, Castelnau-le-Lez, Dr Shadfar Polyclinique de Bordeaux Caudéran, Bordeaux, Dr Casteigt CH Marie Lannelongue, Le Plessis-Robinson, Dr Caussin Hôpital François Mitterrand, Pau, Dr Delarche Hôpital Pasteur, Nice, Dr Ferrari Clinique du Tonkin, Villeurbanne, Dr Champagnac CHU de Poitiers, Dr Christiaens Hôpital Arnaud de Villeneuve, Montpellier, Dr Leclercq Hôpital Cardio-Vasculaire Louis Pradel, Lyon, Dr Finet Hôpital Saint-Joseph, Marseille, Dr D’Houdain Clinique de l’Europe, Amiens, Dr Py Hôpital privé Beauregard, Marseille, Dr Wittenberg CH de Cannes, Drs Tibi/Zemour CHR Strasbourg, Dr Ohlmann Hôpital Cochin, Paris, Dr Varenne CH d’Avignon, Drs Pansieri/Barney Hôpital Cardiologique du Haut Lévêque, Pessac, Dr Coste CH Lens, Dr Pecheux Clinique de l'Orangerie, Strasbourg, Dr Aleil Clinique Nantaise, Nantes, Dr Brunel CH de Compiègne, Dr Sayah Hôpital Pontchaillou, Rennes, Dr Le Breton CH Dijon, Dr Cottin

Centers and principal investigators

Background

Brar S, et al. J Am Coll Cardiol. 2011;58:1945–1954.

P <0.001 85 90 95 100 30 60 90 120 150 180 Time (Days)

Cardiac Death and ST

Dual al Nonresponders

Clopidogrel Nonresponders

Gori AM, et al. J Am Coll Cardiol. 2008;52:734 - 739

GRAVITAS / TRIGGER-PCI designs

Screening 24hrs after PCI with VerifyNow P2Y12 High platelet reactivity (PRU ≥ 230) Clopi High Dose / Prasugrel Clopidogrel Standard Dose igh Dose High Dose H e Dose Clopido Clopido

• Rd

Coronary angiogram Stent-PCI 6-month FU

Price MJ et al. JAMA 2011;305:1097–105 Trenk D et al. J Am Coll Cardiol 2012;59:2159–64.

Standard of care VerifyNow P2Y12 + ASA

Drug (ASA, clopidogrel, prasugrel, GP2b3a I.) and Dose adjustments if high platelet reactivity

Now w Coronary angiogram Stent-PCI Rd Standard of care

Drug (ASA, clopidogrel, prasugrel) and Dose adjustments at day 14

12-month FU Stent-PCI

ARCTIC trial design

Primary endpoint at 12 months:

• Death, MI, stroke, stent thrombosis,

urgent revascularization Statistical considerations:

• Assuming an annual risk of 9% and a

33% relative risk reduction (α risk at 5% and error β at 80%, bilateral test), 2,466 patients were necessary to demonstrate the superiority of the strategy of monitoring and adjustment

ARCTIC study protocol - Collet JP, et al. Am Heart J 2011;161:5-12

Inclusion / Exclusion

• Patients scheduled for planned PCI
• DES implantation
• Consent and Rx before start of PCI
• Primary PCI for STEMI
• Any PCI with planned use of

GPIIbIIa

• BMS or oral anticoagulation

requirement

• Short life expectancy
• Bleeding diathesis

ARU>550 (Aspirin)

GPIIb/IIIa+ clopidogrel (re)LD (>600 mg)

• r prasugrel LD 60 mg then,

MD clopidogrel 150 mg or prasugrel 10mg

DES-PCI %inh<15% and/or PRU>235 (P2Y12)

Adjustment rules

%inh<15% and/or PRU>235

Doubling the aspirin dose ↗ Clopidogrel dose by at least 75 mg or switch to prasugrel 10mg* if clopidogrel 150mg ↘ 75mg if prasugrel clopidogrel 75mg

ARU>550 %inh>90% VerifyNow @ day 14-30

Adjustment rules

Conventional

(n=1227)

Monitoring

(n=1213)

Age - median

63 63

Diabetes - %

37 36

Prior MI - %

31 29

Prior PCI - %

44 42

Prior CABG - %

7 6

Beta blockers - %

60 56

Proton pump inhibitors - %

32 33

Stent implanted - %

98 98

Drug-eluting stent implanted - %

97 97

Baseline characteristics

Conventional (n=1227) Monitoring (n=1213)

Aspirin poor responders - %

NA

7.6

On-table aspirin loading in poor responders - % NA 85 Thienopyridine poor responders - % NA

35

On-table clopi. loading in poor responders - % NA 80 On-table prasu. loading in poor responders - % NA 3.3 On-table GP IIbIIIa loading in poor responders - % NA 80

In-Lab monitoring and adjustment

43% % had ad d their ei r clopidogrel e el MD D increased ed 43% 17% ad d % ha % % were d re re eir cl c e he h th e put on dogre el

• pi

n prasugrel e D D MD M el el MD cr c in D 46% % had ad d their ei r aspirin in n MD D increased ed

High on-clopidogrel reactivity High on-aspirin reactivity Cath lab Day 14

Day-14 monitoring and adjustment

Primary Endpoint to 1 year

Death, MI, stroke, stent thrombosis, urgent revascularization

HR = 1.13 [0.98-1.29] p= 0. 096 Conventional Monitoring

100 200 300

34.6% 31.1%

Conventional Monitoring HR = 1.06 [0.74-1.52] p= 0. 77

100 200 300

4.9% 4.6%

Main Secondary Endpoint to 1 year

Stent thrombosis or urgent revascularization

Primary Endpoint Main Secondary Endpoint

Pre-specified subgroups

Conventional Monitoring

HR [95%CI] P

Death or myocardial Infarction - % 28.8 31.7

1.11 [0.96; 1.29] 0.15

Any death - % 1.6 2.3

1.41 [0.79; 2.50] 0.24

Myocardial infarction - % 28.4 30.3

1.08 [0.93; 1.25] 0.32

Stent thrombosis - % 0.7 1

1.34 [0.56; 3.18] 0.51

Stroke or TIA- % 0.6 0.7

1.15 [0.42; 3.18] 0.78

Urgent revascularization - % 4.2 4.5

1.06 [0.73; 1.55] 0.76

Other Ischemic Endpoints

Conventional Monitoring

HR [95%CI] P

Major bleeding - %

3.3 2.3

0.70 [0.43; 1.14]

0.15

Minor bleeding - %

1.7 1.0

0.57 [0.28; 1.16]

0.12

Major or minor bleeding - %

4.5 3.1

0.69 [0.46; 1.05]

0.08

Key Safety Outcomes

STEEPLE definitions - Montalescot G, et al. N Engl J Med 2006; 355:1006–17

• 1. PFT + antiplatelet therapy adjustment before and after

stenting does not improve clinical outcome as compared with standard treatment without PFT.

• 2. Our data do not support routine use of PFT in patients

undergoing stenting.

• 3. ARCTIC-2 continues: 2nd randomization for continuation vs.

interruption of clopidogrel at 1 year follow-up.

• 4. ANTARCTIC (NCT01538446) evaluates the value of PFT in

the elderly population with a paradigm shift towards safety.

PFT: Platelet Function Testing