The Spanish ESTROFA-2 registry

The Spanish ESTROFA-2 The Spanish ESTROFA-2 registryregistry

Thrombosis in real practice with second Thrombosis in real practice with second generation Drug-eluting stents:generation Drug-eluting stents:

Endeavor, Xience and PromusEndeavor, Xience and Promus

Jose Mª de la Torre Hernandez, MD, PhDInterventional Cardiology Department

Hospital Universitario Marqués de ValdecillaSantander. 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 InterestDisclosure 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 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.

Participating centers

F Gimeno H. C. ValladolidJ A Diarte H. M. Servet, ZaragozaA Perez de Prado H. de LeonJ Sanchis H. Clinico, ValenciaR Lopez Palop H. San Juan, AlicanteF Hernandez H. 12 de Octubre, MadridJA Baz H. Meixoeiro, VigoI Lozano H. Central AsturiasJ Mauri H. G. Trias i Pujol, BadalonaJ M Vazquez H. J. Canalejo, La CoruñaJ M Hernandez H. V. de la Victoria, MalagaJ R Rumoroso H. Galdacano, BilbaoJ M Ruiz Nodar H. G. de AlicanteJ Martin Moreiras H. C. de SalamancaFernando Rivero H. La Princesa, MadridE Pinar H. V. de la Arrixaca, Murcia

Coordinator: Jose Mª De la Torre H.U.M de ValdecillaSantander

M Larman P. Guipuzcoa J Botas H.F. AlcorconJ A Bullones H. Carlos Haya, MalagaB Garcia H. Vall de Hebron BarcelonaJ Moreu H. V. De la Salud, Toledo F Alfonso H. Clinico, MadridJ Elizaga H.G. Marañon, MadridF Bosa H. C. U. de TenerifeR Melgares H. V. de las Nieves, GranadaA Gomez-Jaume H. Son Dureta, P. de

MallorcaA Sanchez Recalde H. La Paz, MadridR Trillo H. C. de S. de CompostelaJL Diez H. Dr. Peset, ValenciaJ D Cascon H. S. M. del Rosell, CartagenaJ A Fernandez H. P. de Hierro, MadridJ Jimenez H. G. AlbaceteJ Diaz H. J. Ramon Jimenez, Huelva

Participating centers

Stent Thrombosis Definition

ZES EESN=1916 N=1413 p

Age (yrs) 66.8 12 65.812 0.01Females 23.2% 23.7% 0.7Diabetes 30.5% 35.2% 0.004HBP 62% 64% 0.2Current smoker 28.7% 30% 0.8Hypercholesterolemia 54% 59% 0.004Renal failure 7.9% 8.7% 0.4LVEF, % 56.3 12 56.4 12 0.9Previous STEMI 18.9% 19% 0.9Previous PCI 21% 24.8% 0.01Previous CABG 5.7% 7.5% 0.04

Clinical characteristics(N=3329)

ZES EESN=1916 N=1413 p

ACS 75.5% 66.6% <0.0001STEMI + non STEMI 49.4% 39% <0.0001N lesions treated 1.45 0.8 1.51 0.8

0.03

Total stent length 34.4 22 35 22 0.4Abciximab 31.7% 28.2% 0.03

ASA+Clopidogrel:

Indefinitely 21% 15% 0.001

Def. (months) 10.9 2 11.2 1.90.001

2778 lesions 2133 lesionsLAD lesion 45% 52% <0.0001Total occlusion 3.2%% 4.4% 0.03Restenosis 4.7% 7% 0.0007Bifurcation 13.8% 16.6% 0.007Calcified 20.1% 20.6% 0.7Stent length (mm) 19.4 6 19.75.5 0.13Stent diameter (mm) 2.99 0.4 2.98 0.4 0.3

Procedural characteristics

1 m 6 m 12 m 18 m

EESPts. at risk 1413 950 347 35

Incidence 0.5%0.5% 1.2%1.2% 1.6%1.6% --

ZESPts. at risk 1916 1560 1004 585

Incidence 1%1% 1.8%1.8% 1.9%1.9% 2.1%2.1%

Definite+probable+possibleStent thrombosis

- - -- - - EES EESZESZES

P = 0.3P = 0.3

1 m 6 m 12 m 18 m

EESPts. at risk 1413 950 347 35

Incidence 0.5%0.5% 0.9%0.9% 1.4%1.4% --ZESPts. at risk 1916 1560 1004 585

Incidence 1%1% 1.4%1.4% 1.5%1.5% 1.8%1.8%

Definite+probableStent thrombosis


P = 0.3P = 0.3

1 m 6 m 12 m 18 m

EESPts. at risk 1413 950 347 35


Incidence 0.6%0.6% 0.9%0.9% 1%1% 1.2%1.2%

DefiniteStent thrombosis


P = 0.3P = 0.3

1 m 6 m 12 m 18 m

Pts. at risk 694 530 320 130Incidence 0.7%0.7% 1.1%1.1% 1.1%1.1% 1.6%1.6%

STEMI casesSTEMI cases(73% with ZES)(73% with ZES)


1 m 6 m 12 m 18 m

EESPts. at risk 190 138 81 9


Incidence 0.7%0.7% 1.3%1.3% 1.3%1.3% 1.9%1.9%

STEMI casesSTEMI cases



P=0.5P=0.5

No thrombosis Def. + prob. thrombosis

N=3292 N=37 p

Age (yrs) 66.4 12 7012 0.06Females 23.4% 29.7% 0.5Diabetes 32.5% 54% 0.009HBP 63% 94% 0.0002Current smoker 28% 15% 0.1Hypercholesterolemia 56% 54.5% 0.9Renal failure 8.3% 17.2% 0.1LVEF, % 56.3 12 52.3 12.5 0.04Previous STEMI 19% 17.6% 0.9Previous PCI 22.6% 25.7% 0.8Previuos CABG 6.5% 10.8% 0.5

Differential characteristics in cases with and without thrombosis

No thrombosis Def. + prob. thrombosis

N=3292 N=37 p

ACS 71.7% 78.4% 0.5STEMI + non STEMI 45% 48.6% 0.7N lesions treated 1.47 0.8 1.67 10.1

Total stent length 34.6 22 39 22 0.1Abciximab 30% 27% 0.8

4850 lesions 61 lesionsLAD lesion 48% 52.5% 0.5Total occlusion 3.7%% 3.3% 0.8Restenosis 5.7% 4.9% 0.9Bifurcation 15% 21.3% 0.3Calcified 20.3% 20.6% 0.8Stent length (mm) 19.6 6 229 0.02Stent diameter (mm) 2.99 0.4 2.8 0.4 0.001

Differential characteristics in cases with and without thrombosis

Antiplatelet therapy indefinite and probable thrombosis

No late Laten=23 n=14

ASA+clopidogrel 21 10ASA 2Clopidogrel 1ASA + oral AC 1None 2*

Early dual txcessation 2 (8.7%) 2 (8.7%) 1 (7.1%)1 (7.1%)

Cessationof ASA mono-TX nana 1 (7.1%)1 (7.1%)

** Bleeding events Bleeding events

Definite + probable thrombosisNo late Late N=23 N=14 p

Females 17.4% 43% 0.1

Age 66.9 12 76 9.7 0.02

STEMI + non STEMI 34.7% 57% 0.3

ACS 65.2% 93% 0.1

LVEF 54 13 46 11 0.06

Lesions treated 1.47 0.8 2.1 1.50.1

Total stent length 35.5 22 43.2 25 0.3

Stent diameter 2.75 0.35 2.85 0.33 0.4

Differential characteristics in cases with late vs non-late thrombosis

HR (CI 95%) p

Age 1.037 (1.008-1.06) 0.01Diabetes 2.5 (1.374.5) 0.02Renal failure 2.3 (1.007-5.2) 0.04LVEF 0.97 (0.94-0.99) 0.03HBP 12 (2.9-50) 0.0006Stent length 1.03 (1.009-1.08) 0.04Stent diameter 0.48 (0.2-0.99) 0.03----------------------------------ZES 1.59 (0.81-3.1) 0.2

Univariant analysis for predictors ofdefinite and probable stent thrombosis

HR (CI 95%) p

LVEF 0.96 (0.94-0.99) 0.03

Stent diameter 0.35 (0.15-0.84) 0.02

HBP 7.3 (1.7-31) 0.007

-------------------

ZES 1.3 (0.6-2.9) 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 1st generation DES (1 yr definite thrombosis 1.2-1.7% (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;293:2126-2130 4 Daemen J et al. Lancet 2007;369:667-82 Ong A et al. J Am Coll cardiol 2005; 45: 2088-92 5 De la Torre et al. J Am Coll Cardiol 2008;51:986-903 Kuchulakanti PM et al. Circulation 2006; 113 : 1108-13

The Spanish ESTROFA-2 registry

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