DUREE de la BITHERAPIE dans les ETUDES LEADERS. J BERLAND Clinique Saint Hilaire ROUEN

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1 DUREE de la BITHERAPIE dans les ETUDES LEADERS J BERLAND Clinique Saint Hilaire ROUEN

2 LEADERS all-comers Trial Design Stable and ACS Patients Undergoing PCI Assessor-blind 1:1 Randomisation N=1700 Patients 10 European centers BioMatrix Flex (BES)* N=850 Cypher Select (SES) N=850 1:3 Randomisation Clinical F/U N=640 Angio F/U N=210 Clinical F/U N=640 Angio F/U N=210 1 o endpoint: MACE: Cardiac death, MI, clinically-indicated TVR (9 mo) 2 o endpoints: Death, CV death, MI, TLR, TVR Stent thrombosis according to ARC Angiographic study: In-stent % diameter stenosis (9 mo) Late loss, binary restenosis DAPT recommended for 12 months

3 Antiplatelet Agent Utilization BES SES P value* Aspirin At 1 year 786/810 (97%) 770/801 (96%) 0.32 At 2 years 749/789 (95%) 733/777 (94%) 0.60 At 3 years 714/757 (94%) 709/748 (95%) 0.69 At 4 years 694/745 (93%) 681/730 (93%) 0.93 Clopidrogel or ticlopidine At 1 year 552/810 (68%) 534/801 (67%) 0.53 At 2 years 185/789 (23%) 189/774 (24%) 0.68 At 3 years 148/757 (20%) 153/749 (20%) 0.67 At 4 years 119/745 (16%) 135/730 (18%) 0.21 Dual antiplatelet therapy At 1 year 536/810 (66%) 513/801 (64%) 0.37 At 2 years 171/789 (22%) 168/777 (22%) 0.98 At 3 years 126/757 (17%) 133/749 (18%) 0.57 At 4 years 96/745 (13%) 111/730 (15%) 0.21 * P values for superiority Ischinger et al., oral presentation, TCT 2011

4 % Definite Stent Thrombosis (ARC) BES SES 1-year RR 0.99 ( ) P=0.98* 2% 2% 2-year RR 0.90 ( ) P=0.73* 2.5% Δ year RR 0.78 ( ) P=0.43* 2.9% Δ % 2.2% 4-year RR 0.62 ( ) P=0.09* 4% Δ % Months Number s at risk SES BES * P values for superiority Stefanini G. et al., The Lancet, 2011 Ischinger et al., oral presentation, TCT 2011

5 % Definite ST Landmark 1 Year 6 SES 5 4 BES 0 to 1 year RR 0.99 ( ) P=0.98* 1 to 4 year RR 0.20 ( ) P=0.004* % 2.0% % 0.4% Months after index PCI No. at risk SES BES P for interaction=0.017 Stefanini G. et al., The Lancet, 2011 Ischinger et al., oral presentation, TCT 2011 * P values for superiority

6 % Effect of DAPT Discontinuation EN Rev.01 3,0 2,5 2,0 Overall Population 2,2 2,9 P = 0.12* Patient who d/c DAPT 2,4 BES SES 1,5 1,0 P = 0.24* 0,5 0, Y ST in LEADERSST after DAPT d/c < 12 M 0,4 N=0/165 N=4/169 N=0/540 N=2/515 ST after DAPT d/c > 12 M *P values for superiority (Fisher Exact Test) 7

7 (%) LEADERS - OCT 9 Months Lesions With At Least 5% Uncovered Struts (-61.7 to 10.3) P< ,3 20 BES 29 Lesions SES 35 Lesions ,5 BES SES 29 Lesions 35 Lesions Barlis P et al. Eur Heart J 2010, 31(2):

8 RECOMMENDATIONS EUROPEENNES 2010

9 AHA CLOPIDOGREL après implantation de STENT ACTIF: L OPTION COURTE J BERLAND SAINT HILAIRE ROUEN SFC ACC ESC HIGH TECH 2009 ARGUMENTAIRE CONTRE UNE MAUVAISE IDEE TOUTE FAITE: PROLONGER LE PLAVIX SYSTEMATIQUEMENT

10 ETUDES RANDOMISEES SUR LA DUREE DE LA DOUBLE AAP après STENT ACTIF Trial Also comparing stents Devices DAPT duration (months) Thrombotic events Bleeding events Status DES LATE (n=2 701) No SES, PES, ZES 12 vs. 24 No difference (card.death, MI) No difference (TIMI maj.) Published (NEJM 2010) PRODIGY (n=2 013) No BMS(25%), ZES, PES, EES 6 vs. 24 No difference (death,mi,cva) 6 mth better (BARC) Published (Circulation 2012) RESET (n=2 117) Yes E-ZES vs. SES, EES, ZES EXCELLENT (n=1 443) 3 (E-ZES) vs.12 (other DES) No difference (death,mi,st) Yes EES & SES 6 vs. 12 No difference (TVF) No difference No difference (TIMI maj.) Published (JACC 2012) Published (Circulation 2012) DAPT (n=20 000) No DES (15 000) BMS (5 000) 12 vs. 30 NYK NYK Ongoing OPTIMIZE (n=3 120) No E-ZES 3 vs. 12 NYK NYK Ongoing ZEUS (n=1 600) Yes ZES vs. BMS 1 (stable) 6+ (ACS) NYK NYK Ongoing ISAR-SAFE 6 000) (n= ISAR TRIPLE (n= 600) No DES 6 vs. 12 NYK NYK Ongoing No DES 1.5 vs. 6 (all on AVK) NYK NYK Ongoing

11 ETUDES RANDOMISEES SUR LA DUREE DE LA DOUBLE AAP après STENT ACTIF Trial Also comparing stents Devices DAPT duration (months) Thrombotic events Bleeding events Status DES LATE (n=2 701) No SES, PES, ZES 12 vs. 24 No difference (card.death, MI) No difference (TIMI maj.) Published (NEJM 2010) PRODIGY (n=2 013) No BMS(25%), ZES, PES, EES 6 vs. 24 No difference (death,mi,cva) 6 mth better (BARC) Published (Circulation 2012) RESET (n=2 117) Yes E-ZES vs. SES, EES, ZES 3 (E-ZES) vs.12 (other DES) No difference (death,mi,st) No difference Presented (ACC 2012) EXCELLENT (n=1 443) Yes EES & SES 6 vs. 12 No difference (TVF) No difference (TIMI maj.) Published (Circulation 2012) DAPT (n=20 000) No DES (15 000) BMS (5 000) 12 vs. 30 NYK NYK Ongoing OPTIMIZE (n=3 120) No E-ZES 3 vs. 12 NYK NYK Ongoing ZEUS (n=1 600) Yes ZES vs. BMS 1 (stable) 6+ (ACS) NYK NYK Ongoing ISAR-SAFE 6 000) (n= No DES 6 vs. 12 NYK NYK Ongoing ISAR TRIPLE (n= 600) No DES 1.5 vs. 6 (all on AVK) NYK NYK Ongoing

12 XIENCE V USA: THROMBOSE DE STENT entre 30 j et 1AN Après interruption de la double anti-agrégation

13 ETUDES CLINIQUES DU XIENCE pour le marquage CE INERRUPTION DES ANTI-AGREGANTS à 3 MOIS

14 THROMBOSES DE STENT et INTERRUPTION DES AAP ETUDES sur LE XIENCE

15 RECOMMENDATIONS EUROPEENNES 2010

16 Birth of a concept (May 2011) Current DAPT trend : «shorter is better» A new polymerfree metallic stent A forgotten patient population Urban, oral presenation, EuroPCR 2012

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19 Main inclusion criteria Age 75 years Oral anticoagulants needed after PCI Planned major surgery (within next year) Baseline Hb <11 g/dl or TF during prior 4 weeks Hospital admission for bleeding during past year Any prior intra-cerebral bleed Any stroke during the past year Cancer diagnosed or treated < 3 years Urban, oral presenation, EuroPCR 2012

20 Main inclusion criteria Age 75 years Oral anticoagulants needed after PCI Planned major surgery (within next year) Baseline Hb <11 g/dl or TF during prior 4 weeks Hospital admission for bleeding during past year Any prior intra-cerebral bleed Any stroke during the past year Cancer diagnosed or treated < 3 years Urban, oral presenation, EuroPCR 2012

21 Trial design Two stents Biosensors BioFreedom BA9 Drug-Coated Coronary Stent (DCS). Biosensors Gazelle Bare Metal Coronary Stent (BMS) One DAPT regimen ASA mg OD, indefinitely Clopidogrel 75 mg OD (or another P2Y12 inhibitor) for one month only Urban, oral presenation, EuroPCR 2012

22 LEADERS FREE Trial Design PI: Philip Urban Prospective, multi-center, multi-national, double blinded randomized trial High Bleeding Risk PCI population (ACS + Elective stable patients) 2500 patients in 60 centers worldwide BioFreedom DCS 1:1 randomization Gazelle BMS Clinical Follow-Up 1 mo 2 mo 4 mo 1 yr 2 yr Primary safety endpoint: Primary efficacy endpoint: Composite of cardiac death, MI, definite/probable stent thrombosis at 1 year (Non-inferiority) Clinically driven TLR at 1 year (Superiority) DAPT mandated for 1 month only, followed by long term SAPT

23 RECOMMENDATIONS EUROPEENNES 2015 Durée de la double Antiagrégation Plaquettaire après STENT ACTIF 3 mois pour les patients standards avec stents actifs de seconde génération. I C 1 mois pour les patients à haut risque hémorragique Avec le stent BIOFREEDOM I A