The Spanish ESTROFA2 registry Thrombosis in real practice

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, Ph. D 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 offlabel usage, . . . ). • Industry-independent, large-scale registries without exclusion criteria yielded a linearly growing rate of thrombosis with 0. 4 -0. 6% 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 Gimeno F Alfonso J A Diarte A Perez de Prado J Sanchis R Lopez Palop F Hernandez JA Baz I Lozano J Mauri J M Vazquez J M Hernandez J R Rumoroso J Martin Moreiras F Rivero E Pinar H. Clinico, Valladolid H. C. San Carlos, Madrid H. M. Servet, Zaragoza H. de Leon, Leon H. Clinico, Valencia H. San Juan, Alicante H. 12 de Octubre, Madrid H. Meixoeiro, Vigo H. Central Asturias, Oviedo H. G. Trias i Pujol, Badalona H. J. Canalejo, La Coruña H. V. de la Victoria, Malaga H. Galdacano, Bilbao H. C. de Salamanca, Salamanca H. La Princesa, Madrid H. V. de la Arrixaca, Murcia Coordinator: Jose Mª De la Torre H. U. M de Valdecilla Santander

Investigators and centers M Larman J Botas J A Bullones B Garcia J Moreu J Elizaga F Bosa R Melgares A Gomez-Jaume A Sanchez Recalde R Trillo JL Diez J D Cascon J A Fernandez J Jimenez J Diaz JC Fernandez A Serra P. Guipuzcoa, San Sebastian H. F. Alcorcon, Alcorcon H. Carlos Haya, Malaga H. Vall de Hebron, Barcelona H. V. De la Salud, Toledo H. G. Marañon, Madrid H. C. U. de Tenerife, Stª Cruz de Tenerife H. V. de las Nieves, Granada H. Son Dureta, Palma de Mallorca H. La Paz, Madrid H. C. de S. de Compostela H. Dr. Peset, Valencia H. S. M. del Rosell, Cartagena H. P. de Hierro, Madrid H. G. Albacete H. J. Ramon Jimenez, Huelva H. de Jaen, Jaen H. del Mar, Barcelona

Stent Thrombosis Definition

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

Clinical characteristics (N = 4768) Age (yrs) Females Current smoker Diabetes HBP Hypercholesterolemia Renal failure LVEF, % Previous STEMI Previous PCI Previous CABG ZES N=2549 EES N=2219 p 66. 8 11. 8 23. 6% 29. 2% 31. 5% 60% 51. 5% 7. 5% 56. 4 12 18. 8% 21. 3% 66. 2 11. 5 24. 1% 27. 2% 36. 3% 58. 7% 53. 9% 7% 56. 5 13 19. 1% 24. 7% 7. 4% 0. 07 0. 1 0. 0005 0. 37 0. 1 0. 5 0. 9 0. 8 0. 006 0. 1

Procedural characteristics ZES N=2549 EES N=2219 p ACS N lesions treated 75. 4% 1. 44 0. 8 68. 9% 1. 47 0. 76 <0. 0001 0. 1 Total stent length Stent diameter (mm) ASA+Clopidogrel: Months 34. 8 23 2. 95 0. 4 34. 5 24 2. 98 0. 4 0. 6 0. 01 11 2 11. 2 1. 9 0. 004 3670 lesions 3261 lesions 3. 4% 3. 7% 13. 2% 20% 3. 9% 6. 2% 14. 4% 20. 5% Total occlusion Restenosis Bifurcation Calcified 0. 2 0. 0001 0. 7

Definite + probable + possible Stent thrombosis - - - EES ZES P = 0. 03 1 m 12 m 24 m Pts. at risk 2219 2010 640 Incidence ZES 0. 5% 1% 1. 2% Pts. at risk 2549 2350 1044 Incidence 0. 9% 1. 8% 2. 4% EES

Definite + probable Stent thrombosis Ac-Subac. Late Very late ZES 55% 33% 12% - - - EES ZES EES 56% 38% 6% P = 0. 1 1 m 12 m 24 m Pts. at risk 2219 2010 640 Incidence ZES 0. 5% 0. 9% 1. 1% Pts. at risk 2549 2350 1044 Incidence 0. 9% 1. 5% 1. 8% EES

Definite Stent thrombosis - - - EES ZES P = 0. 2 1 m 12 m 24 m Pts. at risk 2219 2010 640 Incidence ZES 0. 3% 0. 5% 0. 7% Pts. at risk 2549 2350 1044 Incidence 0. 5% 0. 9% 1% EES

Propensity score matched groups Clinical characteristics Age (yrs) Females Current smoker Diabetes HBP Hypercholesterolemia Renal failure LVEF, % ZES N=1300 EES N=1300 p 68± 11. 5 25. 5% 26. 7% 30. 2% 65. 8% 54. 3% 8. 9% 57 ± 12 67. 8 ± 11 24. 2% 26. 6% 32. 5% 64. 2% 56. 2% 8. 4% 56. 7 ± 13 0. 6 0. 5 0. 9 0. 2 0. 4 0. 3 0. 7 0. 5

Propensity score matched groups Procedural characteristics ZES N=1300 EES N=1300 p ACS N lesions treated 71. 4% 1. 48 ± 0. 8 70. 3% 1. 49 ± 0. 8 0. 5 0. 7 Total stent length Stent diameter (mm) ASA+Clopidogrel: Months 35. 6 ± 23 2. 94 ± 0. 4 35. 2 ± 24 2. 95 ± 0. 4 0. 6 0. 5 11 ± 2 11. 1 ± 1. 9 0. 2 1924 lesions 1937 lesions 3. 8% 1% 13. 8% 20. 2% 4% 13. 4% 20. 3% Total occlusion Restenosis Bifurcation Calcified 0. 8 0. 2 0. 7 0. 9

PROPENSITY SCORE MATCHED GROUPS - - - EES ZES Definite + probable + possible Stent thrombosis P = 0. 13 1 m 12 m 24 m Pts. at risk 1300 1268 402 Incidence ZES 0. 5% 1. 2% 1. 5% Pts. at risk 1300 1207 575 Incidence 0. 9% 1. 9% 2. 5% EES

PROPENSITY SCORE MATCHED GROUPS - - - EES ZES Definite + probable Stent thrombosis P = 0. 3 1 m 12 m 24 m Pts. at risk 1300 1268 402 Incidence ZES 0. 5% 1% 1. 3% Pts. at risk 1300 1207 575 Incidence 0. 9% 1. 4% 1. 9% EES

PROPENSITY SCORE MATCHED GROUPS - - - EES ZES Definite Stent thrombosis P = 0. 4 1 m 12 m 24 m Pts. at risk 1300 1268 402 Incidence ZES 0. 3% 0. 4% 0. 7% Pts. at risk 1300 1207 575 Incidence 0. 6% 0. 8% 0. 9% EES

Differential characteristics in cases with and without thrombosis No thrombosis N=4703 Age (yrs) Females Diabetes HBP Current smoker Hypercholesterolemia Renal failure LVEF, % 66. 5 12 23. 8% 33. 7% 59. 4% 28. 3% 52. 6% 7. 3% 56. 5 12 Def. + prob. thrombosis N= 65 p 70. 6 12 29. 2% 43% 76. 9% 18. 4% 44. 6% 16. 9% 50. 9 15 0. 007 0. 5 0. 1 0. 006 0. 1 0. 3 0. 01 0. 0006

Differential characteristics in cases with and without thrombosis No thrombosis N= 4703 Def. + prob. thrombosis N= 65 p ACS STEMI N lesions treated Total stent length Stent length (mm) Stent diameter (mm) 72. 3% 17. 4% 1. 46 0. 8 34. 7 23 19. 4 6 2. 97 0. 4 75. 4% 10. 7% 1. 61 1 40 23 22. 8 9 2. 82 0. 35 0. 6 0. 2 0. 1 0. 07 0. 001 Total occlusion Restenosis Bifurcation 3. 6%% 4. 9% 13. 7% 6. 1% 4. 6% 23% 12% 24. 6% 20% 21. 5% 0. 2 0. 9 0. 009 0. 1 0. 8 -Double stenting Calcified

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%

Independent predictors for definite + probable stent thrombosis HR (CI 95%) p LVEF Bifurcations Stent diameter 0. 96 (0. 94 -0. 99) 2 (1. 02 -4) 0. 28 (0. 1 -0. 7) 0. 01 0. 04 0. 006 Acute-Subacute LVEF Bifurcations Stent diameter 0. 96 (0. 93 -0. 99) 3. 7 (1. 5 -9. 3) 0. 26 (0. 07 -0. 91) 0. 03 0. 005 0. 03 Late-Very late Age 1. 06 (1. 008 -1. 12) 0. 03 ACS, STEMI and DES type were not predictors

Conclusions • 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 1. 2 -1. 7% vs 0. 7 -1% ¡Incidence increase in definite thrombosis from 1 st to 2 nd year 0. 4 -0. 6% 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.