Real World Data on Stent Thrombosis: The Spanish ESTROFA registry Jose Mª de la Torre Hernandez, MD, PhD Interventional Cardiology Department Hospital Universitario Marqués de Valdecilla Santander SPAIN

The author has no conflicts of interest to disclose

Felipe Hernandez H. 12 de octubre Madrid Main investigator: Dr. Jose Mª de la Torre Hernandez Santander Felipe Hernandez H. 12 de octubre Madrid Marcelo San Martin H. Meixoeiro Vigo Iñigo Lozano H. Central Asturias Oviedo Josefina Mauri H. G. Trias i Pujol Badalona Armando Perez de Prado H. de Leon Leon Jose M. Vazquez H. Canalejo La Coruña Juan Sanchis H. C. de Valencia Valencia Jose M. Hernandez H. V. de la Victoria Malaga J. R. Rumoroso H. Galdacano Bilbao Jose A. Diarte H. M. Servet Zaragoza Juan M. Ruiz Nodar H. G. de Alicante Alicante Javier Rodriguez H. C. de Salamanca Salamanca J.R. Lopez Minguez H. I. Cristina Badajoz Eduardo Pinar H. V. de la Arrixaca Murcia F. Alfonso H. C. de Madrid Madrid Jose M. de la Torre H. M. de Valdecilla Santander

DES Usage in Spain Use of DES in Spain has grown (5% in 2002 to 52% in 2005) over time and across centers 2002 2003 2004 2005 2% to 30% 12% to 45% 18% to 70% 36% to 73%

ESTROFA: Site & Patient Selection 17 centers across Spain with 400 to 1300 PCI / year DES use at study sites: 20% to 73% Data Collection: Detailed report (standardized) of every DES thrombosis since the introduction of DES in each institution, retrospective and prospective. Detailed characterization (standardized data-base) of all the patients treated with DES and no-ST Adjudication process by independent-one person MD event review No funded According to confidential regulations in Spain.

ESTROFA: Stent Thrombosis Definition Angiographic documentation of complete occlusion (TIMI flow grade 0 or 1) or presence of flow limiting thrombus (TIMI flow grade 2 or 3) within or adjacent to a previously successfully implanted DES. For cases > 1 month after procedure an associated acute coronary syndrome had to be present

ESTROFA: Follow-Up Clinical follow up was obtained from the hospital registries and medical records where clinical data of the patient visits were collected For patients who had events at another hospital, medical records and discharge summaries were requested Clinical follow up to 4 years (median 18 months)

ESTROFA: Preliminary Results (15 Centers) Overall stent thrombosis 162 (1,2%) SES PES 1,35% 1.1% p=0,2 Acute (< 24h) 20 (0,15%) Subacute (1-30 days) 76 (0,56%) Late ( 1-6 months) Very late (> 6 months)* 15 (0,11%) 51 (0,37%) * Vey late: Median 11,4 months; range 6-46 months

ESTROFA: DES thrombosis treatment and outcomes In- hospital outcome Outcomes Late Follow-up (13 10 m) 82% presented as STEMI 18% presented with cardiogenic shock 7 pts died (5 cardiac: 4 sudden, 1 post-CABG) 4 re-thrombosis 3 pts underwent CABG 1 pt had a heart transplant (4 on waiting list with ICD) 6 pts had a new PCI Thrombectomy 58 (36%) New stent implanted (DES 55%) 72 (44%) Abciximab 120 (74%) TIMI III obtained 146 (90%) In-hospital deaths Re- thrombosis 14 (8,6%) 4 (2,4%)

ESTROFA: outcomes for Late vs non-Late events Acute/Subacute Late N=96 N=66 Death 11 (11,4%) 10 (15%) ns In hospital 7 (7,3%) 7 (10,6%) In follow up 4 (4,5%) 3 (5%) Re-Thrombosis 5 (5,2%) 3 (4,5%) ns

Risk factors for DES Thrombosis No thrombosis Thrombosis N=13338 N=162 p value Age (yrs) 63 11 6012 0,006 Males 77% 75% 0,8 Diabetes 29% 30% 0,8 HBP 46% 47% 0,8 Renal failure 3% 5% 0,2 LVEF, % 54 11 50 11 0,02 ACS 58% 80% <0,0001 STEMI 12% 38% <0,0001 LAD lesion 50% 71% <0,0001 Total occlusion 11% 20% 0,0005 Restenosis 9% 13% 0,1 Bifurcation (2 stents) 3% 6% 0.14 Stent length (mm) 19 7 2510 <0,0001 Stent diameter (mm) 2,86 0,3 2,83 0,4 0,5 Abciximab 15% 27% <0,001

ESTROFA: antiplatelet therapy at the time of thrombosis <6 months >6 months N=111 N=51 ASA+Clopidogrel 76 (68%) 2 (4%) ASA 13 (12%) 35 (68%) -Early dual disc. 12 2 Clopidogrel 10 (9%) 2 (4%) -Early dual disc. 10 1 Coumadin 0 1 (2%) Nothing 12 (11%) 11 (21,5%) Early dual disc. 12 2 Disc. of ASA - 9 Early stop dual tx 30,6% 10% Stop mono Tx -- -- 17,6% Time to thrombosis after non-early stop of Clopidogrel: -median 155 days -range (32-1280 days)

Differential characteristics in ACUTE-SUBACUTE vs LATE events Acute/Subacute Late p N=96 N=66 Age 61 ±12 58 ±13 0,09 Females 31% 15% 0,03 Diabetes 38% 20% 0,02 Renal insuf. 8% 0% 0,04 EF 53 ±11 49 ±11 0,07 LAD 70% 77% 0,4 ACS 85% 76% 0,2 STEMI 35% 41% 0,5 Stent length 26 ±12 23 ± 11 0,06 Stent diameter 2,78 ±0,3 2,9 ±0,4 0,05 Stent subexpansion by angio. 23% 9% 0,03 Cypher 30% Taxus 10%

Differential characteristics in ACUTE-SUBACUTE vs LATE vs VERY LATE Ac/Subac. Late Very Late <1m 1-6m >6m n=96 n=15 n=51 Age 61 ±12 63 ±12 56,5 ±12 * Males 69% 74% 88%* Diabetes 38% 40% 14%* Renal insuf. 8% 0% 0%* EF 53 ±11 48 ±14 52 ±10 ACS 85% 86% 73% STEMI 35% 40% 41% LAD 70% 73% 78,4% Stent length 26 ±12 25 ±10 22 ±12* Stent diameter 2,78 ±0,3 2,85 ±0,4 2,92 ±0,4* Stent subexp by angio. 23% 0% 12% * p<0,05 for comparison Ac/Sub. vs Very late

ESTROFA: Independent predictors for Acute and Sub-acute stent thrombosis OR (CI 95%) p value ACS 2,7 (1,4-5) 0,002 STEMI 4 (2,8-6) 0,0001 Renal insuf. 4,7 (1,7-13) 0,002 Female sex 2 (1,25-3) 0,008 LAD 2,1 (1,3-3,4) 0,002 Stent Length (per mm ) 1,08 (1,06-1,1) 0,0001 Vessel 2,5mm 1,7 (1,07-2,7) 0,03

ESTROFA: Independent predictors for Late stent thrombosis OR (CI 95%) p value STEMI 7,5 (4-14) 0,0001 LAD 3,9 (2,1-7,2) 0,0001 Stent length 1,06 (1,02-1,08) 0,004

ESTROFA: Independent predictors for Very Late stent thrombosis OR (CI 95%) p value STEMI 6,2 (3-13) 0,0001 LAD 3,5 (1,8-7) 0,0003

TOTAL 13500 pts LAD Rest 6750 (50%) 6750 Thrombosis rates 6750 (50%) 6750 Thrombosis rates Total 1,7% 0,68% Acute-subacute 0,9% 0,5% Late (1-6m) 0,22% 0% Very late (>6m) 0,6% 0,18%

TOTAL 13500 pts STEMI Rest 1620 (12%) 11880 Thrombosis rates 1620 (12%) 11880 Thrombosis rates Total 3,8% 0,8% Acute-subacute 2,1% 0,5% Late (1-6m) 0,4% 0,06% Very late (>6m) 1,3% 0,25%

TOTAL 13500 pts STEMI-LAD Rest 800 (6%) 12700 Thrombosis rates 800 (6%) 12700 Thrombosis rates Total 5,6% 0,9% Acute-subacute 2,75% 0,58% Late (1-6m) 0,75% 0,07% Very late (>6m) 2,1% 0,26%

ESTROFA Conclusions Documented stent thrombosis was infrequent (1.2% overall) with DES The incidence up to 6 months (~ 0.82%) seems similar to that seen with BMS The incidence after 6 months was approximately 0.4% for both Cypher and Taxus DES, and is higher than BMS In our experience overall ST incidence tended to be numerically, but not significantly, higher with SES compared to PES. Main predictors of stent thrombosis < 6 months include: -Inadequate antiplatelet therapy, STEMI, LAD, longer stent length, small stent diameter and renal failure Of these, only the STEMI indication and LAD location were predictors of stent thrombosis after 6 months The risk of ST is very low (0.8%) in patients without STEMI.