The Spanish ESTROFA-2 registry Thrombosis in real practice with second generation Drug-eluting stents: Endeavor, Xience and Promus Jose Mª de la Torre Hernandez, MD, PhD Interventional Cardiology Department Hospital Universitario Marqués de Valdecilla Santander. SPAIN Spanish Working Group Interventional Cardiology

I, Jose Mª de la Torre Hernandez, DO NOT have a financial interest/arrangement or affiliation with one or more organizations that could be perceived as a real or apparent conflict of interest in the context of the subject of this presentation. Disclosure Statement of Financial Interest

Rationale for the registry The experience with first generation DES (Cypher® and Taxus ®) showed that randomized trials do not reflect the risk for late thrombosis associated with their use in real practice (frequent off-label usage,...). Industry-independent, large-scale registries without exclusion criteria yielded a linearly growing rate of thrombosis with % per year. Second generation DES (Endeavor ®, Xience ® and Promus ®) based in new platforms, polymers and drugs (Zotarolimus and Everolimus), have shown to be safe and effective in randomized trials but, Again, we need registries from real practice to ascertain the risk for late thrombosis with these new DES according to current definitions.

Methods 34 centers throughout Spain (public tertiary hospitals) Data Collection: Web-based CRF (supported by the Spanish Working Group on Interventional Cardiology) Detailed forms (clinical and procedural) for all patients treated with Everolimus-eluting stents (EES) or Zotarolimus-eluting stents (ZES) until April / 08. Systematic clinical follow up of all patients in: May 2008 May 2009 Detailed forms for all cases with definite, probable or possible stent thrombosis. Adjudication process by independent-one person MD event review According to confidential regulations in Spain.

Participating centers F GimenoH. C. Valladolid J A DiarteH. M. Servet, Zaragoza A Perez de PradoH. de Leon J SanchisH. Clinico, Valencia R Lopez PalopH. San Juan, Alicante F HernandezH. 12 de Octubre, Madrid JA BazH. Meixoeiro, Vigo I LozanoH. Central Asturias J MauriH. G. Trias i Pujol, Badalona J M VazquezH. J. Canalejo, La Coruña J M HernandezH. V. de la Victoria, Malaga J R RumorosoH. Galdacano, Bilbao J M Ruiz NodarH. G. de Alicante J Martin MoreirasH. C. de Salamanca Fernando RiveroH. La Princesa, Madrid E PinarH. V. de la Arrixaca, Murcia Coordinator: Jose Mª De la Torre H.U.M de Valdecilla Santander

M LarmanP. Guipuzcoa J BotasH.F. Alcorcon J A BullonesH. Carlos Haya, Malaga B GarciaH. Vall de Hebron Barcelona J MoreuH. V. De la Salud, Toledo F AlfonsoH. Clinico, Madrid J ElizagaH.G. Marañon, Madrid F BosaH. C. U. de Tenerife R MelgaresH. V. de las Nieves, Granada A Gomez-JaumeH. Son Dureta, P. de Mallorca A Sanchez RecaldeH. La Paz, Madrid R TrilloH. C. de S. de Compostela JL DiezH. Dr. Peset, Valencia J D CasconH. S. M. del Rosell, Cartagena J A FernandezH. P. de Hierro, Madrid J JimenezH. G. Albacete J DiazH. J. Ramon Jimenez, Huelva Participating centers

Stent Thrombosis Definition

ZESEES N=1916N=1413p Age (yrs) Females23.2%23.7%0.7 Diabetes30.5%35.2%0.004 HBP62%64%0.2 Current smoker28.7%30%0.8 Hypercholesterolemia54%59%0.004 Renal failure7.9%8.7%0.4 LVEF, % Previous STEMI18.9%19%0.9 Previous PCI21%24.8%0.01 Previous CABG5.7%7.5%0.04 Clinical characteristics (N=3329)

ZESEES N=1916N=1413p ACS75.5%66.6%< STEMI + non STEMI 49.4%39%< N lesions treated Total stent length Abciximab31.7%28.2%0.03 ASA+Clopidogrel: Indefinitely21%15%0.001 Def. (months) lesions2133 lesions LAD lesion45%52%< Total occlusion3.2%4.4%0.03 Restenosis4.7%7% Bifurcation 13.8%16.6%0.007 Calcified20.1%20.6%0.7 Stent length (mm) Stent diameter (mm) Procedural characteristics

1 m6 m12 m18 m EES Pts. at risk %1.2%1.6% Incidence 0.5%1.2%1.6% -- ZES Pts. at risk %1.8%1.9%2.1% Incidence 1%1.8%1.9%2.1% Definite+probable+possible Stent thrombosis EES ZES P = 0.3

1 m6 m12 m18 m EES Pts. at risk %0.9%1.4% Incidence0.5%0.9%1.4%-- ZES Pts. at risk %1.4%1.5%1.8% Incidence1%1.4%1.5%1.8% Definite+probable Stent thrombosis EES ZES P = 0.3

1 m6 m12 m18 m EES Pts. at risk %0.5%0.9% Incidence0.3%0.5%0.9% -- ZES Pts. at risk %0.9%1%1.2% Incidence0.6%0.9%1%1.2% Definite Stent thrombosis EES ZES P = 0.3

1 m6 m12 m18 m Pts. at risk %1.1%1.1%1.6% Incidence0.7%1.1%1.1%1.6% STEMI cases (73% with ZES) Definite+probable Stent thrombosis

1 m6 m12 m18 m EES Pts. at risk %0.7%0.7% Incidence0.7%0.7%0.7% -- ZES Pts. at risk %1.3%1.3%1.9% Incidence0.7%1.3%1.3%1.9% STEMI cases Definite+probable Stent thrombosis EES ZES P=0.5

No thrombosisDef. + prob. thrombosis N=3292N=37p Age (yrs) Females23.4%29.7%0.5 Diabetes32.5%54%0.009 HBP63%94% Current smoker28%15%0.1 Hypercholesterolemia56%54.5%0.9 Renal failure8.3%17.2%0.1 LVEF, % Previous STEMI19%17.6%0.9 Previous PCI22.6%25.7%0.8 Previuos CABG6.5%10.8%0.5 Differential characteristics in cases with and without thrombosis

No thrombosisDef. + prob. thrombosis N=3292N=37p ACS71.7%78.4%0.5 STEMI + non STEMI 45%48.6%0.7 N lesions treated Total stent length Abciximab30%27% lesions61 lesions LAD lesion48%52.5%0.5 Total occlusion3.7%3.3%0.8 Restenosis5.7%4.9%0.9 Bifurcation 15%21.3%0.3 Calcified20.3%20.6%0.8 Stent length (mm) Stent diameter (mm) Differential characteristics in cases with and without thrombosis

Antiplatelet therapy in definite and probable thrombosis No lateLate n=23n=14 ASA+clopidogrel2110 ASA2 Clopidogrel1 ASA + oral AC1 None2* Early dual tx 2 (8.7%) 1 (7.1%) cessation 2 (8.7%) 1 (7.1%) Cessation na1 (7.1%) of ASA mono-TX na1 (7.1%) * Bleeding events

Definite + probable thrombosis No late Late N=23N=14p Females17.4%43%0.1 Age STEMI + non STEMI 34.7%57%0.3 ACS65.2%93%0.1 LVEF Lesions treated Total stent length Stent diameter Differential characteristics in cases with late vs non-late thrombosis

HR (CI 95%)p Age1.037 ( )0.01 Diabetes2.5 ( )0.02 Renal failure2.3 ( )0.04 LVEF0.97 ( )0.03 HBP12 (2.9-50) Stent length1.03 ( )0.04 Stent diameter0.48 ( ) ZES1.59 ( )0.2 Univariant analysis for predictors of definite and probable stent thrombosis

HR (CI 95%)p LVEF0.96 ( )0.03 Stent diameter0.35 ( )0.02 HBP7.3 (1.7-31) ZES1.3 ( )0.49 Multivariant analysis for predictors of definite and probable stent thrombosis

In this registry the incidence at 1 year of definite + probable stent thrombosis was 1.4% for everolimus-eluting stents and 1.5% for zotarolimus-eluting stents. This incidence results slightly lower compared to the reported with 1 st generation DES (1 yr definite thrombosis % (1-5) vs 1%) This could be attributable to a combined effect of: drug-eluting stent, better case selection, improved implantation technique and higher antiplatelet therapy adherence No significant differences were found between EES and ZES. Ejection fraction, hypertension and stent diameter were independent predictors for thrombosis. Stent use in myocardial infarction was not associated with a higher incidence of thrombosis. A longer follow up is needed to determine the incidence of thrombosis over following years. Conclusions 1 Colombo A et al. JAMA 2005;293: Daemen J et al. Lancet 2007;369: Ong A et al. J Am Coll cardiol 2005; 45: De la Torre et al. J Am Coll Cardiol 2008;51: Kuchulakanti PM et al. Circulation 2006; 113 :