Supplementary Appendix
PROTECT steering committee
E Camenzind (Chairman), University of Geneva, Geneva, Switzerland
L Mauri, Brigham and Women's Hospital, Boston, MA, USA
W O'Neill, University of Miami Miller School of Medicine, Miami, FL, USA
P W Serruys, Erasmus MC, Thoraxcentrum, Rotterdam, the Netherlands
PhG Steg, INSERM U-1148, Université Paris Diderot, DHU-FIRE, AP-HP, Hôpital Bichat, Paris,
France. NHLI, Royal Brompton Hospital, Imperial College, London, UK
W Wijns, OLV Hospital, Aalst, Belgium
Data safety monitoring board (DSMB)
FWA Verheugt (Chairman), Lieve Vrouwe Gasthuis, Amsterdam, the Netherlands
ME Bertrand, Hôpital Cardiologique, Lille, France
R Califf, Duke Health ORG, Durham, NC, USA
D DeMets, University of Wisconsin Madison, Madison, Wisconsin, USA
L Wallentin, Akademiska Sjukhuset, Uppsala, Sweden
Clinical event committee (CEC)
W Bocksch, Universitaitsklinikum Tubbingen, Tubbingen, Germany
J Bosmans, UZA, Edegem, Belgium
H Garcia, Erasmus Medisch centrum, Rotterdam, the Netherlands
S Garg, Royal Blackburn Hospital, Blackburn, United Kingdom
C Hanet, Cliniques Universitaires Saint-Luc, Brussels, Belgium
J-PR Herrman, Onze Lieve VrouweGasthuis, Amsterdam, the Netherlands
H Kelbaek, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark
E Mc Fadden, Cork University Hospital, Wilton, Cork, Ireland
PW Radke, Universitätsklinikum Schleswig-Holstein, Lübeck, Germany
W Rutsch, Akademisches Lehrkrankenhaus der, Charité Universitätsmedizin Berlin, Berlin,
Germany
HH Tilsted, Aalborg Hospital, Aalborg, Denmark
J Wykrzykowska, Academisch Medisch Centrum, Amsterdam, the Netherlands
Independent statistician
E Boersma, University Medical Center Rotterdam Erasmus, Rotterdam, the Netherlands
Supplementary Figure Legend
Supplmentary Figure 1. Usage of dual antiplatelet therapy at discharge, 6 months, and
annually through 4 years. E-ZES=Endeavor zotarolimus-eluting stent. C-SES=Cypher
sirolimus-eluting stent.
Dual antiplatelet therapy defined as aspirin and a thienopyradine (clopidogrel, ticlopidine, or
other).
Supplementary Figure 2. Anticipated 3-year (A) and actual 4-year (B) rates of definite or
probable stent thrombosis
A. Anticipated 3-year rate
B. Actual 4-year rate
E-ZES=Endeavor zotarolimus-eluting stent. C-SES=Cypher sirolimus-eluting stent.
Supplementary Table 1. List of Investigators in PROTECT
Country (patients enrolled)
Site
Investigator
Argentina (n=6)
Hospital Italiano Regional del Sur
C Alvarez
Country (patients enrolled)
Site
Investigator
Sanatorio Otamendi
A Rodriguez
Southern Health, Monash Medical Center
I Meredith
St Vincent's Sydney
D Muller
St Vincent's Melbourne
R Whitbourn
Royal Adelaide
S Worthley
Fremantle
A Whelan
The Prince Charles Hospital
D Walters
Royal Perth Hospital
S Shetty
Box Hill Hospital
G New
The Wesley Hospital
S Cox
Gold Coast Hospital
R Batra
Northern Hospital
W van Gaal
John Hunter Hospital
G Bellamy
Landesklinikum St Pölten
H Mayr
Salzburger Landeskliniken
M Hammerer/ M Heigert
Wilhelminensp der Stadt Wien
K Huber
AKH Linz
C Steinwender/ F Leisch
OLVrouwziekenhuis
W Wijns
UZ Leuven (Gasthuisberg)
W Desmet
CHR Citadelle
J Boland
Cliniques Universitaires UCL
E Schroeder / P Chenu
CHU Sart-Tilman
V Legrand
Ottawa Heart Institute
M Labinaz
London Health Sciences Center
P Teefy
Hôpital Laval
O Bertrand
Beijing Fuwai Hospital
R Gao
Zhongshan Hospital Fudan Univ
J Ge
Faculty Hospital Brno Bohunice
P Kala
Mas Hospital Usti nad Labem
P Cervinka
Dominican Republic (n=44)
CEDIMAT
P Ureña
Finland (n=29)
Kuopio University Hospital
J Hartikainen
Australia (n=414)
Austria (n=144)
Belgium (n=265)
Canada (n=52)
China (n=252)
Czech Republic (n=19)
Country (patients enrolled)
Site
Investigator
France (n=952)
AP-HP, Hôpital Bichat
PG Steg
Clinique Pasteur
J Fajadet
CHU Rangueil - Toulouse
D Carrie
Hôpital de la Cavale Blanche, Brest
M Gilard
Polyclinique des Fleurs
P Barragan
CHU Lille
A Sudre / J-M Lablanche
Clinique Saint-Hilaire, Rouen
R Koning
Hôpital Charles Nicolle-CHU Rouen
H Eltchaninoff
Clinique Saint Augustin
O Darremont
Polyclinique de la Louvière
F Leroy
CHU Michallon – Grenoble
B Bertrand
Clinique Saint- Pierre
G Robert
CHU Jean Minjoz – Besancon
F Schiele
Clinique Saint-Gatien, Tours
S Chassaing
Nouvelles Cliniques Nantaises
E Bressollette / P Brunel
Hôpital Trousseau – CHU
L Quilliet
Clinique Rhone-Durance
J Brunet
Hôpital Henri Duffaut
M Pansieri
AP-HP Hôpital Lariboisiere
G Sideris / V Stratiev
AP-HP, Hôpical Henri Mondor
E Teiger
Hôpital Pontchaillou - Rennes
H Lebreton
Hôpital La Timone, Marseille
J-L Bonnet
Clinique Saint Martin
B Karsenty
CH Pau
N Delarche
CHU Clermont Ferrand
J-R Lusson / J Cassagnes
Klinikum Coburg
J Brachmann
Universitätsklinikum Lübeck
V Kurowski
M Luther UnivKlin Kröllwitz
M Buerke
Med Hochschule Hannover
A Schäfer / B Schieffer
Herz- und Diabeteszentrum
W Scholtz / M Wiemer
Klinikum der J W Goethe Univ
S Fichtlscherer / V Schächinger
Germany (n=1369)
Country (patients enrolled)
Site
Investigator
Klinikum der Univ München Großhadern
C Kupatt / P Boekstegers
Klinikum der J Gutenberg Univ
T Münzel / S Genth-Zotz
Universitätsklinikum Freiburg
C Bode
Universitätsklinikum Heidelberg
N Frey
Herz Zentrum Bad Krozingen
F-J Neumann
Charité - Campus B Franklin
C Skurk / B Witzenbichler / K Pels
Herzzentrum Dresden
R Strasser
Asklepios Klinik St Georg
K-H Kuck
Krankenh der Barmh Brüder
K-E Hauptmann
Univ Klinikum Hamburg-Eppendorf
K Sydow / S Baldus / T Heitzer
Lukas Krankenhaus
M Haude
Klinikum Bogenhausen
E Hoffmann
Klinikum Villingen-Schwenningen
W Jung
Vivantes Klin im Friedrichshain
H Ince / S Hoffmann
Städtisches Klinikum Karlsruhe
C Schmitt
Vivantes Humboldt-Klinikum
M Dissmann
Klinikum Nürnberg
M Pauschinger
Städtische Kliniken Darmstadt
G Werner
University Magdeburg
R Braun-Delleus
Marienhof Koblenz
D Burkhardt / M Manz
Onassis Cardiac Surgery Center
V Voudris
1st IKA
D Sionis
Queen Elizabeth Hospital
M-L Kang-Yin
Pamela Youde Nethersole Eastern Hospital
T-S Tse
Hungary (n=107)
Semmelweis University
B Merkely
India (n=506)
Jaslok Hospital & Res Centre
A Mehta
The Heart Care Clinic
K Parikh
Max Heart and Vascular Institute
V Kumar / P Chandra
Apollo Hospital, Hyderabad
P Rath
Ruby Hall Clinic
S Hiremath
St James' Hospital
P Crean
Greece (n=55)
Hong Kong (n=59)
Ireland (n=33)
Country (patients enrolled)
Site
Investigator
University Hospital Galway
K Daly
Rabin Med Center, Belinson Campus
R Kornowski
Rambam Medical Center
A Kerner
Meir MC
M Mosseri
Barzilay MC
G Jafari
Az Osp S Giovanni di Dio e Ruggi D'Aragona
P Giudice
Policlinico "A Gemelli"
C Trani
Ospedale S Maria Nuova
A Manari
Ospedale S Giovanni - Addolorata
F Prati
Ospedale Lancisi
G Gabrielli / A Pangrazi
S Donato USL 8
L Bolognese
Chonnam University Hospital
M-H Jeong
Dong-A University Hospital
M-Y Kim
Seoul Nat Univ Hospital
H-S Kim
ASAN Medical Center
S-J Park
P Stradins University Hospital
A Erglis
Hospital "Gailezers"
A Kalnins
Luxembourg (n=1)
INCCI
D Wagner
Malaysia (n=74)
National Heart Institute (IJN)
R Zambahari
Sarawak General Hospital
T-K Ong / K Sim
Amphia Ziekenh Molengracht
P den Heijer
VU Medisch Centrum
Y Appelman
St Antonius Ziekenhuis
M-J Suttorp
Univ Med Centrum Groningen
E Lipsic / B de Smet
Catharina Ziekenhuis
J Koolen
Univ Medisch Centrum Utrecht
P Stella
Wellington Hospital
S Harding
Ascot Integrated Hospital
J Warwick / A Maslowski
Wakefield Hospital
M Abernethy
Waikato Hospital
G Devlin
Haukeland Universitets Sykehus
S Rotevatn
Israel (n=64)
Italy (n=123)
(South) Korea (n=254)
Latvia (n=126)
Netherlands (n=535)
New Zealand (n=85)
Norway (n=34)
Country (patients enrolled)
Site
Investigator
Feiringklinniken
Y Myreng
SPSK No1, ACK AMG
D Ciecwierz
WSS imdr WlBieganskiego
J Peruga
4 Wojskowy Szpital Kliniczny
K Reczuch
Hospital Santa Cruz
R Campante Teles
Hospital Fernando Fonseca
P Farto E Abreu
Centro Hospital de Coimbra
A Leitão-Marques
Hospital Garcia Orta
H Pereira
Romania (n=54)
Univ Hospital of Bucharest
D Vinereanu
Saudi Arabia (n=262)
Prince Sultan Cardiac Center
S Alkasab
King Fahd Medical City
H Mhish / M Al Kurdi
King Faisal Specialist Hospital
F Al Turki
National Heart Center
P Wong
National University Hospital
S-G Teo
Hospital Puerta de Hierro
F-J Goicolea Ruigomez
Hospital Vírgen de la Arrixaca
M Valdés Chávarri
Hospital de Son Dureta
A Bethencourt Gonzalez
Hospital de Meixoeiro
A Iñiguez Romo
Hospital Infanta Cristina
J López Minguez
Hospital Clín Univ V Victoria
J-M Hernández García
Hospital Juan Ramón Jiménez
J Diaz Fernández
Hospital Univ V de la Macarena
R Ruiz Salmeron
Hospital Univ La Princesa
A Benedicto / L Martinez Elbal
Hospital Univ Marqués Valdecilla
J Zueco
Hospital de San Juan de Alicante
RF López-Palop
Hospital Virgen de las Nieves
R Melgares
Centrallasarettet Västerås
E Diderholm / A Kåregren / O
Herterich
Universitetssjukhuset i Lund
G Olivencrona
Universitetssjukhuset Örebro
O Fröbert
Hôpitaux Universitaire Genève
M Roffi / V Verin
Centre Hospitalier Universitaire Vaudois
G Girod
Poland (n=86)
Portugal (n=177)
Singapore (n=34)
Spain (n=328)
Sweden (n=201)
Switzerland (n=63)
Country (patients enrolled)
Taiwan (n=66)
UK (n=1658)
USA (n=178)
Site
Investigator
Kantonsspital Aarau AG
A Vuilliomenet
Chang Gung Memorial Hospital LK
I-C Hsieh
Chang Gung Mem Hospital KS
C-J Wu
Glenfield Hospital
A Gershlick
Papworth Hospital
C Densem
Queen Elizabeth Medical Centre
S Doshi
Royal Victoria Hospital
G Manoharan
King's College Hospital
P McCarthy
James Cook University Hospital
M De Belder
Cardiothoracic Centre
J Mills
Manchester Royal Infirmary
F Fath-Ordoubadi
Southampton General Hospital
I Simpson
Leeds General Infirmary
J Greenwood
Cheltenham General Hospital
R Chamberlain-Webber / Z Khan
New Cross Hospital
J Cotton
City General Hospital
M Gunning
Morriston
D Smith
Royal Bournemouth
S Talwar
Royal Sussex County Hospital
S Holmberg
Freeman
I Purcell
University Hospital of Wales
R Anderson
Castle Hill Hospital
S Thackray / F Alamgir
Mayday Hospital
N Goulielmos / K Beatt
Basildon Hospital CTC
P Kelly
Sharp Chula Vista Med Center
M Moussavian
Cooper University Hospital
J Aji
Ocala Regional Medical Center
R Prashad
Dallas VA Medical Center
J Hastings / A Zankar / S Banerjee
Bethesda North Hospital
S Lewis
AnMed Health
B McLaurin
Emory University Hospital
J Douglas
Country (patients enrolled)
Site
Investigator
Methodist Hospital
S Brener
Aurora St Lukes
A Gupta
University Hospital - Augusta
L Walters
Bridgeport Hospital
M Driesman
Baptist Hospital - Pensacola FL
R Aycock
Doctors Hospital at Renaissance
C Mego
University of Massachusetts
D Fisher
Maimonides Medical Center
R Frankel
Washington Hospital Center
L Satler
Supplementary Table 2A. Baseline Demographics and Patient Characteristics
Characteristic
E-ZES
C-SES
(n = 4357)
(n = 4352)
Age, years
62.3±10.6
62.1±10.7
0.50
Male sex
76.7 (3340/4357)
76.0 (3308/4352)
0.48
Body mass index, kg/m2
27.8±4.4
27.9±4.5
0.24
Diabetes mellitus
26.9 (1174/4357)
28.4 (1236/4352)
0.13
6.5 (285/4357)
7.4 (323/4352)
0.11
Hypertension
64.6 (2814/4357)
63.4 (2759/4352)
0.26
Hyperlipidaemia
61.9 (2695/4357)
62.8 (2734/4352)
0.35
History of smoking
57.7 (2515/4357)
57.4 (2500/4352)
0.80
24.9 (1084/4357)
25.2 (1098/4352)
0.71
Premature coronary artery disease in firstdegree relative (n = 7540)
34.2 (1288/3768)
34.8 (1312/3772)
0.59
Previous myocardial infarction
20.3 (885/4357)
20.8 (907/4352)
0.54
Previous CABG
4.6 (199/4357)
5.1 (224/4352)
0.21
Previous PCI
12.3 (534/4357)
12.8 (556/4352)
0.48
Previous stroke
3.1 (133/4357)
3.1 (136/4352)
0.85
25.8 (1123/4357)
26.0 (1130/4352)
0.85
8.2 (356/4357)
8.8 (384/4352)
0.28
Insulin dependent
Current smoker
p value
Procedure indication
All (acute) myocardial infarctions
ST elevation myocardial infarction
Non–ST-elevation myocardial infarction
17.6 (767/4357)
17.1 (746/4352)
0.57
Unstable angina
18.3 (796/4357)
19.3 (842/4352)
0.21
Stable angina
49.5 (2156/4357)
48.3 (2101/4352)
0.27
Silent ischaemia
6.5 (282/4357)
6.4 (279/4352)
0.93
Left ventricular ejection fraction (%) (n =
4489)
58.8±12.6
58.3±12.6
0.17
Serum creatinine (µmol/L) (n = 8152)
87.6±31.5
88.3±38.4
0.37
Complex patients*
58.0 (2526/4357)
58.1 (2528/4352)
0.93
Data given as percentage (n/N) or mean±standard deviation.
* Defined as placement of a stent in a patient with at least one of the following clinical or lesion
characteristics: renal insufficiency (creatinine level: ≥140 μmol/L [1·6 mg/dL]), ejection fraction: <30%,
acute myocardial infarction ≤72 hours, >1 lesion per vessel, >2 vessels with stents, lesion length >27
mm, bifurcation lesion, lesion in bypass graft, in-stent restenosis, unprotected left main artery, lesion
with thrombus, or total occlusion.7
CABG, coronary artery bypass graft; PCI, percutaneous coronary intervention.
Supplementary Table 2B. Baseline Lesion and Procedure Characteristics
Variable
E-ZES
C-SES
(n = 4357 patients)
(n = 4352 patients)
(n = 6151 lesions)
(n = 6139 lesions)
p value
Lesion characteristics
Vessel location (by lesion)
0.13
Left anterior descending
47.1 (2900/6151)
46.0 (2827/6139)
Left circumflex
23.0 (1417/6151)
22.5 (1380/6139)
Right coronary artery
28.9 (1776/6151)
30.1 (1850/6139)
Left main
0.7 (43/6151)
1.0 (61/6139)
Bypass graft
0.2 (15/6151)
0.3 (21/6139)
Restenosis after previous PTCA
0.3 (18/6150)
0.4 (26/6139)
0.23
In-stent restenosis
1.0 (63/6150)
1.1 (65/6139)
0.86
Chronic total occlusion*
2.9 (177/6149)
2.7 (168/6139)
0.66
Bifurcation
16.9 (1038/6149)
15.9 (977/6139)
0.15
Moderate/severe calcification (vs none or mild)
27.8 (956/6149)
30.2 (1851/6139)
0.004
Tortuosity: moderate or severe (vs mild)
22.7 (1394/6146)
23.0 (1414/6139)
0.68
TIMI flow 0 or 1
15.5 (956/6149)
14.4 (887/6139)
0.09
Thrombus
7.6 (467/6149)
7.9 (486/6139)
0.52
ACC/AHA lesion class B2/C
53.7 (3300/6147)
55.7 (3421/6139)
0.025
Reference vessel diameter (mm)
3.0±0.5 (N=6141)
3.0±0.5 (N=6125)
0.030
Minimal luminal diameter (mm)
0.5±0.4 (N=6142)
0.5±0.4 (N=6127)
0.99
Diameter stenosis (%)
82.8±13.0 (N=6146)
82.7±12.8
(N=6129)
0.79
Lesion length (mm)
17.7±9.3 (N=6141)
17.7±9.1
(N=6125)
0.74
Number of vessels treated per patient
1.20±0.45
1.20±0.46
0.46
Number of lesions treated per patient
1.40±0.71
1.39±0.71
0.84
Number of stents per patient
1.63±0.99
1.59±0.96
0.054
Procedure characteristics
Variable
E-ZES
C-SES
p value
(n = 4357 patients)
(n = 4352 patients)
(n = 6151 lesions)
(n = 6139 lesions)
Total stent length/patient (mm)
31.28±20.80
31.20±20.75
0.85
Number of stents per lesion
1.16±0.49
1.13±0.46
0.001
Lesions with pre-dilatation
67.5 (4152/6151)
69.4 (4262/6140)
0.023
Unfractionated heparin
92.1 (4011/4356)
92.0 (4003/4351)
0.91
Low-molecular-weight heparin
5.0 (216/4356)
5.4 (234/4351)
0.38
Direct thrombin inhibitor
4.2 (182/4356)
3.8 (167/4351)
0.44
Glycoprotein IIb/IIIa inhibitor
17.9 (780/4356)
18.4 (799/4351)
0.60
Residual stenosis (%)
1.9±9.2
2.2±10.1
0.097
TIMI 2/3
99.4 (6116/6151)
99.4 (6104/6139)
1.00
Lesion success†
99.6 (6032/6055)
99.4 (6006/6044)
0.055
Device success‡
96.9 (5869/6055)
95.5 (5773/6044)
<0.0001
Procedure success§
97.0 (4145/4272)
96.9 (4135/4266)
0.75
Peri-procedure medication
Post-procedure characteristics
Data given as percentage (n/N) or mean±standard deviation
* TIMI 0; no unstable angina; no myocardial infarction within 72 hours.
† Attainment of <50% residual stenosis of the target lesion using any percutaneous method.
‡ Attainment of <50% residual stenosis of the target lesion using only the assigned device.
§ Attainment of <50% residual stenosis of all the target lesions and no in-hospital MACE.
ACC/AHA, American College of Cardiology/American Heart Association; PTCA, percutaneous coronary
angioplasty; TIMI, Thrombolysis In Myocardial Infarction.
Supplementary Figures
Supplmentary Figure 1. Usage of dual antiplatelet therapy at discharge, 6 months, and
annually through 4 years.
E-ZES=Endeavor zotarolimus-eluting stent. C-SES=Cypher sirolimus-eluting stent.
Dual antiplatelet therapy defined as aspirin and a thienopyradine (clopidogrel, ticlopidine, or
other).
Supplementary Figure 2. Anticipated 3-year (A) and actual 4-year (B) rates of definite or
probable stent thrombosis
A. Anticipated 3-year rate
E-ZES=Endeavor zotarolimus-eluting stent. C-SES=Cypher sirolimus-eluting stent.
B. Actual 4-year rate
E-ZES=Endeavor zotarolimus-eluting stent. C-SES=Cypher sirolimus-eluting stent.