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

The authors have no conflicts of interest to disclose

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.

Investigators and centers F GimenoH. Clinico, Valladolid F AlfonsoH.C. San Carlos, Madrid J A DiarteH. M. Servet, Zaragoza A Perez de PradoH. de Leon, 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, Oviedo 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 Martin MoreirasH. C. de Salamanca, Salamanca F 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, San Sebastian J BotasH.F. Alcorcon, Alcorcon J A BullonesH. Carlos Haya, Malaga B GarciaH. Vall de Hebron, Barcelona J MoreuH. V. De la Salud, Toledo J ElizagaH.G. Marañon, Madrid F BosaH. C. U. de Tenerife, Stª Cruz de Tenerife R MelgaresH. V. de las Nieves, Granada A Gomez-JaumeH. Son Dureta, Palma 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 JC FernandezH. de Jaen, Jaen A SerraH. del Mar, Barcelona Investigators and centers

StentThrombosisDefinition Stent Thrombosis Definition

4768 pts Treated with EES or ZES from 2006 to april-2008 EES 47%ZES 53% Populationincluded Population included

ZESEES N=2549N=2219p Age (yrs)66.8   Females23.6%24.1%0.7 Current smoker29.2%27.2%0.1 Diabetes31.5%36.3% HBP60%58.7%0.37 Hypercholesterolemia51.5%53.9%0.1 Renal failure7.5%7%0.5 LVEF, %56.4   Previous STEMI18.8%19.1%0.8 Previous PCI21.3%24.7%0.006 Previous CABG6.3%7.4%0.1 Clinicalcharacteristics (N = 4768) Clinical characteristics (N = 4768)

ZESEES N=2549N=2219p ACS75.4%68.9%< N lesions treated1.44   Total stent length34.8   Stent diameter (mm)2.95   ASA+Clopidogrel: Months 11   lesions3261 lesions Total occlusion3.4%3.9%0.2 Restenosis3.7%6.2% Bifurcation 13.2%14.4%0.1 Calcified20%20.5%0.7 Proceduralcharacteristics Procedural characteristics

- - - EES ZES P = m12 m24 m EES Pts. at risk %1%1.2% Incidence0.5%1%1.2% ZES Pts. at risk %1.8%2.4% Incidence0.9%1.8%2.4% Definite + probable + possible Stent thrombosis

1 m12 m24 m EES Pts. at risk %0.9%1.1% Incidence0.5%0.9%1.1% ZES Pts. at risk %1.5%1.8% Incidence0.9%1.5%1.8% Definite + probable Stent thrombosis EES ZES P = 0.1 ZESEES Ac-Subac.55%56% Late33%38% Very late12%6%

Definite Stent thrombosis EES ZES P = m12 m24 m EES Pts. at risk %0.5%0.7% Incidence0.3%0.5%0.7% ZES Pts. at risk %0.9%1% Incidence0.5%0.9%1%

ZESEES N=1300N=1300p Age (yrs)68± ± Females25.5%24.2%0.5 Current smoker26.7% 26.6%0.9 Diabetes30.2%32.5%0.2 HBP65.8%64.2%0.4 Hypercholesterolemia54.3%56.2%0.3 Renal failure8.9%8.4%0.7 LVEF, %57 ± ± Propensity score matched groups Clinical characteristics

ZESEES N=1300N=1300p ACS71.4%70.3%0.5 N lesions treated1.48 ± ± Total stent length35.6 ± ± Stent diameter (mm)2.94 ± ± ASA+Clopidogrel: Months 11 ± ± lesions1937 lesions Total occlusion3.8%4%0.8 Restenosis1%1.4%0.2 Bifurcation 13.8%13.4%0.7 Calcified20.2%20.3%0.9 Propensity score matched groups Procedural characteristics

P = m12 m24 m EES Pts. at risk %1.2%1.5% Incidence0.5%1.2%1.5% ZES Pts. at risk %1.9%2.5% Incidence0.9%1.9%2.5% EES ZES Definite + probable + possible Stent thrombosis PROPENSITY SCORE MATCHED GROUPS

P = m12 m24 m EES Pts. at risk %1%1.3% Incidence0.5%1%1.3% ZES Pts. at risk %1.4%1.9% Incidence0.9%1.4%1.9% EES ZES Definite + probable Stent thrombosis PROPENSITY SCORE MATCHED GROUPS

P = m12 m24 m EES Pts. at risk %0.4%0.7% Incidence0.3%0.4%0.7% ZES Pts. at risk %0.8%0.9% Incidence0.6%0.8%0.9% EES ZES Definite Stent thrombosis PROPENSITY SCORE MATCHED GROUPS

No thrombosisDef. + prob. thrombosis N=4703N= 65p Age (yrs)66.5   Females23.8%29.2%0.5 Diabetes33.7%43%0.1 HBP59.4%76.9%0.006 Current smoker28.3%18.4%0.1 Hypercholesterolemia52.6%44.6%0.3 Renal failure7.3%16.9%0.01 LVEF, %56.5   Differential characteristics in cases with and without thrombosis

No thrombosisDef. + prob. thrombosis N= 4703N= 65p ACS72.3%75.4%0.6 STEMI17.4%10.7%0.2 N lesions treated1.46   10.1 Total stent length34.7  2340  Stent length (mm)19.4   Stent diameter (mm)2.97   Total occlusion3.6%6.1%0.2 Restenosis4.9%4.6%0.9 Bifurcation 13.7%23% Double stenting12%24.6% 0.1 Calcified20%21.5%0.8 Differential characteristics in cases with and without thrombosis

Antiplatelet therapy in definite + probable thrombosis Early discontinuation of dual therapy 1 definite ZES thrombosis ( bleeding ) 1 probable ZES thrombosis ( no compliance ) Discontinuation of mono-therapy 1 probable ZES thrombosis ( bleeding ) 6%

HR (CI 95%)p LVEF0.96 ( )0.01 Bifurcations2 (1.02-4)0.04 Stent diameter0.28 ( )0.006 Acute-Subacute LVEF0.96 ( )0.03 Bifurcations3.7 ( )0.005 Stent diameter0.26 ( )0.03 Late-Very late Age1.06 ( )0.03 Independent predictors for definite + probable stent thrombosis ACS, STEMI and DES type were not predictors

In this registry the incidence at 2 years of definite + probable stent thrombosis was 1.5% and for definite thrombosis was 0.9%. The increase in incidence between 1 st and 2 nd year was 0.3% for definite + probable stent thrombosis and 0.2% for definite thrombosis   This incidence results lower compared to the reported with 1 st generation DES   1 yr definite thrombosis % vs 0.7-1%   Incidence increase in definite thrombosis from 1 st to 2 nd year % vs 0.2%   This could be attributable to a combined effect of: drug-eluting stent, better case selection and higher antiplatelet therapy adherence / longer time. No significant differences were found between EES and ZES. Ejection fraction, stent diameter and bifurcations were independent predictors for subacute thrombosis. Age was predictor for late thrombosis. Stent use in ACS was not associated with a higher incidence of thrombosis. Conclusions