DAPT y DES Dr. Fausto Feres Instituto de Cardiología Dante Pazzanese São Paulo- Brasil Dr. Juan Gaspar Centro Cardiovascular Montevideo -Uruguay

A- 3 meses C- 12 meses B- 6 meses D- 24 meses E- Siempre ¿Por cuánto tiempo mantiene usted al paciente en terapia antiplaquetaria dual luego del implante de un DES? A- 3 meses B- 6 meses C- 12 meses D- 24 meses E- Siempre

A- 3 meses C- 12 meses B- 6 meses D- 24 meses E- Siempre ¿Por cuánto tiempo mantiene usted al paciente en terapia antiplaquetaria dual luego del implante de un DES? A- 3 meses B- 6 meses C- 12 meses D- 24 meses E- Siempre

Terapia antiplaquetaria dual: ¿Por cuánto tiempo? ¿Por qué el DAPT para siempre?

Duke Database Death/MI Analysis Adjusted death/MI rates at 24 months in patients without events at 6 months Clopidogrel status at 6 months Overall P value = 0,07; Pint = 0,12 Clopidogrel status at 12 months Overall P value < 0,001; Pint = 0,003 N=637 N=579 N=417 N=1976 N=252 N=276 N=346 N=1644 Eisenstein EL et al. JAMA 2007;297: on line

Temporal Trends in DAPT Compliance and Incidence of ST while On or Off Thienopyridine Therapy Is Thienopyridine Discontinuation a Cause or Epiphenomenon? Thienopyridine Adherence Over Tim Airoldi F, Colombo A, et al. Circulation. 2007;116:745-54.

Relación entre la descontinuación de las tienopiridinas y la ST VLST 360 – 540 days (0.2%) LST 180 – 360 days (0.3%) 58 Patients with Stent Thrombosis LST 30 – 180 days (0.4%) SAT (0.9%) 60 120 180 240 300 360 420 480 540 Days post-PCI Median time from clopidogrel discontinuation and ST: ST within first 6 months: 13.5 days (IQR range, 5.2 to 25.7) ST after the first 6 months: 90 days (IQR, 30 to 365 days) Airoldi F, Colombo A, et al. Circulation. 2007;116:745-54.

58 cases of ST through 540 Days (1.9%) Tasa de ST en pacientes en terapia antiplaquetaria dual y en pacientes que descontinuaron la terapia con tienopiridinas 0.16 0.14 Pacientes que descontinuaron la terapia con tienopiridinas 0.12 0.10 58 cases of ST through 540 Days (1.9%) 0.08 Event Rates 0.06 0.04 Pacientes que NO descontinuaron la terapia con tienopiridinas 0.02 0.00 60 120 180 240 300 360 420 480 540 No. of Patients Discontinued Thienopyridine 258 422 560 1128 1180 1680 2044 2138 2251 On Thienopyridine 2750 2576 2411 1829 1771 1245 865 756 634 * Aalen-Nelson estimate of cumulative hazard function Airoldi F, Colombo A, et al. Circulation. 2007;116:745-54.

Cumulative Incidence of ARC Def/Prob ST over 4 yrs after DES (CYPHER & TAXUS) 5.7% [95% CI] CYPHER & TAXUS (n=8,146) Bern-Rotterdam2 5 4 3 Cumulative Incidence, % 2 1 1 2 3 4 4 Time since PCI in years 2 Wenaweser et al. J Am Coll Cardiol 2008;52:1134-40

Late Incomplete Stent Apposition What is the real incidence ? Is it a predictor for late stent thrombosis ? Why does it happen ? Cypher ® 1216 days post procedure Taxus ™ 331 days post procedure Hong M e cols. Circulation. 2004;109:881-886. Serruys PW e cols. Circulation. 2002;106:798-803. Tanabe K e cols. Circulation. 2005;111:900-905.

Late Incomplete Apposition and Late Thrombosis 13 patients with late thrombosis > 1 year post procedure X 144 controls without late thrombosis P < 0,001 Incomplete apposition % ST = Stent Thrombosis Cook S, et al. Circulation. 2007;115:2426-2434.

195 patients with DES Late Incomplete Apposition and Late Thrombosis Late Malaposition Persistent Malapposition Without Malapposition Conclusion : Late Incomplete Apposition in 5.1% Siqueira, et al. European Heart J 2007; 28:1304-1309

Predictors of DES Thrombosis 35 Autopsy Examinations Following Stent Placement (N = 32 DES, 7 BMS) SAT 8/39 stents, LST 11/39 stents All BMS with complete endothelialization Predictors Stent across ostia of major sidebranch Strut penetration of necrotic core Stent malapposition Increasing stent length Hypersensitivity Focal delayed no healing (absence of intima) Joner, Virmani, et al. Circulation. 2005;112:3210.

Dual Antiplatelet Therapy : For How Long and for All ? Why DAP therapy for one year ? Is DAP therapy safe ? Can we avoid it ? Are all stents equal ? One year DAP for all ? Can we use the same data (Cypher and Taxus) to do the prescription of DAP for one year for other DES pts ? For how long ?

Incomplete Stent Apposition Post -Endeavor Implantation: IVUS Findings from a Non-Selected Population 67 pts Endeavor™ Baseline ( after stenting ) 63 pts ( 94 % ) without ISA 4 pts ( 6 % ) with acute ISA Angio / IVUS follow up No pts with late ISA No pts with persistent ISA Feres F et al ACC 2008

OPTIMIzed Duration of Clopidogrel Therapy Following Treatment with the Endeavor Zotarolimus-Eluting Stent in the “Real-World” Clinical Practice OPTIMIZE Trial PI : Fausto Feres

Optimize Trial Minimally selected patients undergoing PCI with implantation of the Endeavor ZES; N=3200 Clopidogrel therapy 3-month N=1.600 12-month N=1.600 Clinical follow-up at 1, 3, 6, and 12 months, and yearly up to 5 years PRIMARY Endpoint: Rates of NACCE (Net Adverse Cardiac and Cerebral Events) at 12 m f-up Death, MI, CVA and major bleeding

Safety of Long-Term Clopidogrel 3 Placebo Controlled Trials P=0.07 P=0.001 P<0.001 N=12,563 1 year FU CURE major bleed NEJM 2001;345;494-502 N=2,116 1 year FU TIMI major bleed JAMA 2002;288:2411-20 N=15,603 2.5 year FU GUSTO major + moderate bleed NEJM 2006;354:1706-17

DATP y Cuadro Clínico Síndromes coronarios agudos sin elevación de la ST Acceso transradial Inhibidores Iib IIIa 600 mg Clopidogrel (menos de 2 hs ) 300 mg Clopidogrel (más de 2 hs)

What is the ‘Optimal’ Trial for the ‘Optimal’ DAPT Duration What is the ‘Optimal’ Trial for the ‘Optimal’ DAPT Duration? DAPT durations, inclusion of BMS, landmarking and ‘event-free’ patients Inclusion Group, N DAPT Duration DES Type 1° Endpoint 2° Endpoint(s) DAPT 20,645 12-month event free 12 vs 30 months All DES D/MI/Stroke at 33 mos Def/prob ST at 33 mos GUSTO Bleeding ISAR-SAFE 6,000 6-month event free 6 vs 12 months D/MI/Stroke/TIMI major bleed at 15 mos Individual component endpoints REAL-LATE 2,000 12-month event free 12 vs 24 months 2-yr Cardiac D/MI ARC ST, Bleeding ZEST-LATE SES, PES, ZES 2-yr D/MI OPTIMIZE 3,120 non-STEMI 3 vs. 12 months Endeavor ZES 1-yr D/MI/Stroke/TIMI major bleed ARC ST SEASIDE 900 non-ACS 6 months 1-yr D/MI/Stroke CYP2C19