magellan

Report
Rivaroxaban compared with enoxaparin for
the prevention of venous thromboembolism
in acutely ill medical patients
Alexander T Cohen
On behalf of the MAGELLAN Steering Committee and Investigators
Potential conflicts
 Dr AT Cohen is a medical consultant for and has received
honoraria, consultancy and clinical trial funding from many
pharmaceutical companies, including:
 Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, BMS,
Daiichi Sankyo, GSK, Johnson and Johnson, Mitsubishi Pharma,
Pfizer, Sanofi-Aventis, Schering Plough and Takeda
 Dr Cohen is an advisor to the UK Government Health Select
Committee, the All-party Working Group on Thrombosis,
Department of Health, and the NHS on the prevention of
venous thromboembolism
 Dr Cohen is also an advisor to Lifeblood: The Thrombosis Charity
and is the founder of the European educational charity the
Coalition to Prevent Venous Thromboembolism
Presentation includes discussion of the following off-label use of a drug or medical device: No
Rivaroxaban is not currently approved for use in the United States
Attributable risk for deep vein thrombosis/
pulmonary embolism
Attributable
risk (%)
(95% CI)
Hospitalization with surgery
23.8
(20.3–27.3)
Hospitalization without surgery
21.5
(17.3–25.6)
Malignant neoplasm
18.0
(13.4–22.6)
Risk factor
Congestive heart failure
9.5
(3.3–15.8)
Neurological disease with
extremity paresis
6.9
(3.5–10.2)
Heit et al, 2002
Medical
patients
3
Contemporary studies of
hospitalized patients
Primary efficacy
endpoint* (%)
TE major
bleeding (%)
Placebo
14.9
1.1
Enoxaparin 40 mg od
5.5
1.7
Placebo
5.0
0.0
Dalteparin
2.8
0.4
Placebo
10.5
0.2
Fondaparinux
5.6
0.2
Placebo
4.0
0.3
Extended enoxaparin
2.5
0.8
Short-term thromboprophylaxis
MEDENOX (1999)1
PREVENT (2004)2
ARTEMIS (2006)3
Extended thromboprophylaxis
EXCLAIM (2010)4
MEDENOX, all venous thromboembolism (VTE) Day 1 to Day 14; PREVENT, asymptomatic
proximal deep vein thrombosis (DVT), symptomatic VTE and sudden death Day 1 to Day 21;
ARTEMIS, all VTE Day 1 to Day 15; EXCLAIM, proximal DVT, symptomatic PE or fatal PE Day 10
to Day 38
TE, treatment-emergent
1. Samama et al, 1999; 2. Leizorovicz et al, 2004; 3. Cohen et al, 2006; 4. Hull et al, 2010
4
Background and study questions
Background
 The optimal duration of thromboprophylaxis (short or extended)
and the acutely ill patient population most likely to benefit from
extended thromboprophylaxis is not well characterized
Study question
 Is 10 days of anticoagulation with rivaroxaban non-inferior
to enoxaparin?
 Is 35 days of anticoagulation with rivaroxaban superior to
enoxaparin followed by placebo?
Cohen et al, 2011
5
MAGELLAN: clinical trial design
Day 10
(6–14)
8,101 patients
randomized
Day 35
(31–39)
Day 90
(83–97)
Oral rivaroxaban 10 mg od 35±4 days
Patients
≥40 years
hospitalized for
acute medical
illness with
decreased level
of mobility
s.c. placebo
10±4 days
R
Follow-up
period
to Day 90
Oral placebo
35±4 days
s.c. enoxaparin
40 mg od 10±4 days
Ultrasonography
on day 10±4
*Events from Day 1 to Day 35
Cohen et al, 2011
Primary efficacy outcome
Day 10 (non-inferiority)
Ultrasonography
on day 35±4
Primary efficacy outcome
Day 35* (superiority)
6
MAGELLAN: study outcomes
Primary efficacy outcome
 Composite of:




Asymptomatic proximal DVT detected by mandatory ultrasonography
Symptomatic DVT (proximal or distal)
Symptomatic non-fatal pulmonary embolism (PE)
VTE-related death
 At Day 10 (test for non-inferiority)
 At Day 35 (test for superiority)
Main safety outcome
 Composite of major bleeding and non-major clinically relevant
bleeding observed not later than 2 days after the last intake of
double-blind study medication (treatment emergent)
Cohen et al, 2011
7
Sample size and assumptions
 Sample size: 2,876 valid patients per group was estimated to
obtain a joint power of at least 90%
Non-inferiority: Day 10
 Assumptions: 2.2% event rate in control group; 1.4% event rate in
the rivaroxaban group; relative risk reduction (RRR) ≥35%
 Non-inferiority margin: 1.5
Superiority: Day 35
 Assumptions: 4.0% event rate in the control group; 2.4% event
rate in the rivaroxaban group; RRR ≥40%
Cohen et al, 2011
Patient flow: Day 10 and Day 35 endpoints
Enoxaparin/placebo
Rivaroxaban
4,050
Randomized
(n=8,101)
4,051
3,997 (99%)
Safety
4,001 (99%)
3,232 (80%)
Modified intent to treat (mITT)
Day 10
3,271 (81%)
2,967 (73%)
Day 35
3,057 (75%)
2,938 (73%)
Per-protocol (PP)
Day 10
2,993 (74%)
2,516 (62%)
Day 35
2,586 (64%)
Patient characteristics*
Age, median (years)
Male (%)
Weight, mean (kg)
Body mass index, mean (kg/m2)
Median duration of hospitalization (days)
Creatinine clearance (%)†
<30 ml/min
30 to <50 ml/min
50 to ≤80 ml/min
>80 ml/min
Race (%)†
White
Asian
Other
*Safety population; †some data missing
Rivaroxaban
(N=3,997)
Enoxaparin/placebo
(N=4,001)
71.0
55.6
77.5
28.2
11.0
71.0
52.6
77.3
28.2
11.0
2
20
37
39
2
20
38
38
69
20
7
69
20
7
Underlying medical conditions*
Rivaroxaban
(N=3,997)
(%)
Enoxaparin/placebo
(N=4,001)
(%)
Acute infectious diseases
46
45
Heart failure
32
33
Acute respiratory insufficiency
27
29
Acute ischemic stroke
17
17
Active cancer
7
7
Acute inflammatory/rheumatic
diseases
4
4
Other medical conditions
1
1
≥2 underlying medical conditions
30
31
Acute medical conditions
*Safety population
Primary efficacy outcome: Day 10*
Rivaroxaban
(n=2,939)
n (%)
78 (2.7)
71 (2.4)
7 (0.2)
6 (0.2)
3 (0.1)
Primary efficacy outcome
Asymptomatic proximal DVT
Symptomatic lower extremity DVT
Symptomatic non-fatal PE
VTE-related death‡
0.713
0
0.968
1.334
1.00 1.50
Relative risk ratio
Superior
Enoxaparin
(n=2,993)
n (%)
82 (2.7)
71 (2.4)
6 (0.2)
2 (<0.1)
6 (0.2)
Noninferior
p=0.0025 for non-inferiority
(one-sided)
Inferior
*PP population, events up to Day 10+5 days; ‡includes cases where PE cannot be ruled out
Primary efficacy outcome: Day 35*
Rivaroxaban
(n=2,967)
n (%)
131 (4.4)
103 (3.5)
13 (0.4)
10 (0.3)
19 (0.6)
Primary efficacy outcome
Asymptomatic proximal DVT
Symptomatic lower extremity DVT
Symptomatic non-fatal PE
VTE-related death‡
0.618 0.771 0.962
0
1.00
Relative risk ratio
Superior
Noninferior
Enoxaparin/
placebo
(n=3,057)
n (%)
175 (5.7)
133 (4.4)
15 (0.5)
14 (0.5)
30 (1.0)
Absolute risk reduction: 1.3%
Relative risk reduction: 22.9%
p=0.0211 for superiority
(two-sided)
Inferior
*mITT population, events up to Day 35+6 days; ‡4 confirmed fatal PEs but includes cases where PE
cannot be ruled out
Safety outcomes
Rivaroxaban
(n=3,997)
Enoxaparin/
placebo
(n=4,001)
n (%)
n (%)
111 (2.8)
RR
p value
49 (1.2)
2.3
<0.0001
24 (0.6)
11 (0.3)
2.2
0.0318
164 (4.1)
67 (1.7)
2.5
<0.0001
43 (1.1)
15 (0.4)
2.9
0.0004
56 (1.4)
19 (0.5)
3.0
<0.0001
19 (0.5)
4 (0.1)
4.8
0.0045
Day 1 to 10 (principal safety outcome)
Clinically relevant bleeding*
Major bleeding
Day 1 to 35 (principal safety outcome)
Clinically relevant bleeding*
Major bleeding
Day 10 to 35
Clinically relevant bleeding*
Major bleeding
*Major plus non-major clinically relevant bleeding
Safety population; treatment-emergent bleeding
Components of major bleeding
Rivaroxaban
(n=3,997)
Day 1 to 10
Enoxaparin/
placebo
(n=4,001)
n (%)
n (%)
24 (0.6)
11 (0.3)
Fall in Hb ≥2g/dL
17 (0.4)
7 (0.2)
Transfusions ≥2 units of blood
15 (0.4)
4 (0.1)
5 (0.1)
1 (<0.1)
Major bleeding*
Fatal
Day 1 to 35
Major bleeding*
43 (1.1)
15 (0.4)
Fall in Hb ≥2g/dL
31 (0.8)
10 (0.2)
Transfusions ≥2 units of blood
24 (0.6)
8 (0.2)
7 (0.2)
1 (0.1)
Fatal
*Patients could have more than 1 event
Other outcomes: Day 35
Outcomes
Rivaroxaban Enoxaparin/placebo
(N=3,997)
(N=4,001)
(%)
(%)
Net clinical benefit*
9.4
7.8
Any cardiovascular event
1.8
1.6
All-cause mortality
5.1
4.8
Liver function
ALT >3× ULN + bilirubin >2× ULN‡
0.2
0.2
*The composite of asymptomatic proximal DVT, symptomatic DVT, symptomatic non-fatal PE,
VTE-related death, treatment-emergent major plus non-major clinically relevant bleeding in the mITT
population
‡Day 90+7 data
Contemporary studies of
hospitalized patients
Primary efficacy
endpoint* (%)
TE major
bleeding
(%)
14.9
1.1
5.5
1.7
Placebo
4.0
0.3
Extended enoxaparin
2.5
0.8
Enoxaparin/placebo
5.7
0.4
Extended rivaroxaban
4.4
1.1
Short-term thromboprophylaxis
MEDENOX (1999)1 Placebo
Enoxaparin 40 mg od
Extended thromboprophylaxis
EXCLAIM (2010)4
MAGELLAN
MEDENOX, all VTE Day 1 to Day 14; EXCLAIM, proximal DVT, symptomatic PE or fatal PE Day
10 to Day 38; MAGELLAN, asymptomatic proximal DVT, symptomatic VTE and VTE-related
death Day 1 to Day 35
TE, treatment-emergent
1. Samama et al, 1999; 2. Leizorovicz et al, 2004; 3. Cohen et al, 2006; 4. Hull et al, 2010
17
Summary
 MAGELLAN met its primary efficacy endpoints
 Day 10: rivaroxaban was non-inferior to enoxaparin in reducing the
risk of VTE
 Day 35: extended thromboprophylaxis was superior to enoxaparin
followed by placebo in reducing the risk of VTE
 Overall bleeding rates were low, but significantly higher in the
rivaroxaban arm across the entire study period
 Rates of other adverse events, including liver and cardiovascular
events, were similar in both arms
18
Conclusion
 MAGELLAN confirms that there is a continued risk of VTE
beyond the initial period of hospitalization or immobilization in
acutely ill patients
 Based on the pre-specified net clinical benefit analysis, a
consistently positive benefit-risk balance was not seen across the
heterogeneous, acutely ill patient population studied, and further
analysis is required to identify which groups of patients in
MAGELLAN may derive benefit from thromboprophylaxis with
rivaroxaban
19
Acknowledgements
Steering Committee: Alexander Cohen MBBS (Chairman); Harry Büller MD PhD;
Alexander Mebazaa MD PhD; Sebastian Schellong MD; Geno Merli MD; Victor Tapson
MD; Russell Hull MBBS; Dayi Hu MD PhD; Lloyd Haskell MD; Theodore Spiro MD
Data Safety and Monitoring Board: Alain Leizorovicz MD (Chairman); Gordon Lowe MD;
Charles Francis MD; Robin Roberts MT; Shotai Kobayashi MD PhD
Bayer: Global Clinical Leader, Theodore Spiro MD; Medical Experts: Eva Mühlhofer MD
& Melanie Hemmrich MD; Statistician: Dr. Horst Beckmann; Study Managers:
Andrea Duszczyszyn, Lynda Fielding, Teresa Twomey; Study Data Manager: Karin Müller;
Johnson & Johnson: Physician: Lloyd Haskell MD
Countries and individual sites: Argentina (7 sites); Australia (11 sites); Austria
(14 sites); Belgium (10 sites); Brazil (8 sites); Bulgaria (8 sites); Canada (13 sites); Chile
(2 sites); China (43 sites); Colombia (8 sites); Croatia (6 sites); Czech Republic (7 sites);
Denmark (5 sites); Estonia (4 sites); Finland (2 sites); France (22 sites); Germany
(27 sites); Greece (10 sites); Hong Kong (2 sites); Hungary (8 sites); India (14 sites);
Indonesia (3 sites); Israel (10 sites); Italy (21 sites); Japan (32 sites); Korea (7 sites);
Latvia (6 sites); Lithuania (10 sites); Luxembourg (2 sites); Malaysia (3 sites); Mexico
(12 sites); The Netherlands (4 sites); New Zealand (3 sites); Norway (4 sites); Pakistan
(3 sites); Peru (7 sites); Poland (14 sites); Portugal (10 sites); Russia (8 sites); Singapore
(6 sites); Slovakia (5 sites); Slovenia (6 sites); South Africa (14 sites); Spain (11 sites);
Sweden (9 sites); Switzerland (6 sites); Taiwan (5 sites); Thailand (3 sites); Turkey
(6 sites); Ukraine (16 sites); UK (7 sites); US (72 sites)
Acknowledgements
INVESTIGATORS: DR. F BOTTARO, DR. H HENDLER, DR. B GRAND, DR. A MYKIETIUK, DR. M HOJMAN, DR. O CABERLOTTO, DR. R SALERNO, PROF. E PILGER, DR. N BAUER,
PROF. P SIOSTRZONEK, PROF. R KIRCHMA, DR. W FORTUNAT, DR. C WENISCH, PROF. DR. A WELTERM, DR. L ERLACHEROA, DR. H-R SCHONR, DR. B BAUER, DR. E GRAFL,
PROF. F KEIL, PROF. P BALCKE, PROF. F WEIDINGE, PROF. H SALEM, DR. M LEYDEN, PROF B CHONG, PROF B CHONG, DR. P CARROLL, DR. D COLQUHOUN, DR D JACKSONA,
PROF. E GANA, PROF. S HALL, DR D SERISIERA, PROF R BAKER, PROF. D BLOCKMANS, DR. K HENDRICKX, DR. H STRIEKWOLD, DR. G VAN ROEY, DR. M-E VANDEN ABEELE,
DR. C JACQUY, DR. A DELOBBE, PROF. A SOUPART, DR. L VAN ZANDWEGHE, DR. A VAN HOOF, PROF. V MINCHEVA, PROF. S MILANOV, DR. L LYUBENOV, DR. S NENKOVA,
DR. D DIMOV, DR. M TASEVA, PROF. Y IVANOV, PROF. D POPOV, DR. B GARICOCHEA, DR. C CAVALHEIRO, DR D CHAMONE, DR. J BIZZACCHI, DR. E FISS, DR. A LOPES,
DR. B VAN BELLEN, DR. R RDO MOREIRA, DR. A SHUAIB, DR. F DUBE, DR. D KUTSOGIANNIS, DR. S VERREAULT, DR. B BUCK, DR. A ROUSSIN, DR. G MODDEL, DR. G STOTTS,
DR. H DESAI, DR. J-M BOULANGER, DR. F SILVER, DR. N DANEAULT, DR. C BERGERON, DR. M BANYAI, PROF. I BAUMGARTNER, PROF. A SCHIFFER, DR. A IMHOF, DR. C JEAN,
DR. P NUSSBAUME, DR. G BUGEDO, DR. H TORRES, PROF. D HU, PROF C WANG, PROF. Y WANG, DR. Y YANG, PROF. Y CHEN, DR C SHEN, PROF. J LIU, PROF. S WU, PROF. W LI,
PROF Z ZHAO, DR. Q XIU, PROF. S-Y ZHANG, DR. T HU, PROF. X YAN, DR. L GAI, DR. Y ZHAO, PROF. Q HUA, PROF. H LI, PROF. J LI, PROF. DP ZHANG, DR. B XU, PROF. Q WAN,
PROF. R CHEN, PROF. S XIAN, DR. Y LIU, PROF. Q GAO, DR. C LIU, DR. G QI, PROF. P CHEN, PROF. S SUN, PROF. K YANG, DR. C WU, PROF. H WANG, PROF. L YANG,
PROF. X QIN, DR. S GUO, PROF. Y SUN, DR. Y WANG, DR. Y-S LI, PROF. Y ZHOU, DR. K-N CHEN, DR. J WU, DR. J ZHANG, DR. D FAJARDO, DR. R BOTERO, DR. R RADA,
DR. L GOMEZ, DR. L URIBE, DR. J CEDANO, DR. J VELASQUEZ, DR. C JARAMILLO, PROF. A LINHART, DR. O MAYER, DR. K GORICAN, DR. V PROCHAZKA, DR. J FIKSA, DR. I MACEL,
DR. J SEDLACEK, PROF. W PETERMA, PROF. B MUHLBAUER, DR. J BARTH, DR. H LAWALL, PROF. C POHL, PROF. T KLOTZ, PROF. J-D. RINGE, PROF. J SCHMIDT LUCK,
DR. T HEINTGES, DR. I SCHOFFAUER, DR. A DORMANN, DR. W THEELEN, DR. F-M. DROUVEN, PROF. C NIEDERAU, PROF. B SANNER, DR. H-R MILSTREY, DR. M BORST,
PROF. J VOM DAHL, DR. H HINDAHL, DR. E STØLBEN, PROF. S SCHELL, DR. J BEYER-WESTENDORF, DR. R VELTKAMP, PROF. S MOBIUS-WINK, PROF. C ESPINO,
PROF. M LESCHKE, PROF. I SCHARRER, DR. H NIELSEN, DR. S AVNSTRØM, DR. C TUXEN, DR. T NIELSEN, DR. O ØSTERGAARD, DR. T UUETOA, DR. T MARANDI, DR. M LEMBER,
DR. O KOLBASSOVA, DR. M MONREAL, DR. A CASTRO, DR. C TOLOSA, DR. F CONGET, DR. JA NIETO RODRIGU, DR. R TIRADO MIRANDA, DR. A MARIA GUIL, DR. J BISBE,
DR. F CERETO CASTRO, DR. J TRUJILLO SANTOS, DR. J VILLALTA, DR. R LASSILA, DR. J KARMAKOSKI, PROF. P MISMETTI, PROF. D MOTTIER, PROF. J SCHMIDT, PROF. I QUERE,
PROF. C LE JEUNNE, PROF. D VITAL-DURAND, PROF. I MAHE, DR. R RIHANI, PROF. J-F BERGM, PROF. P DEBOURDEAU, DR. M LAMBERT, PROF. D STEPHAN, PROF. B LORCERIE,
PROF. P LACROIX, DR. A PROUST, PROF. D FARGE-BAN, PROF. C-H MARQUETTE, DR. D BRISOT, DR. C FOURNIER, DR. A DUCHEMIN, DR. S AQUILANTI, PROF. M GALINIER,
DR. M SCULLY, DR. A COHEN, DR. P KESTEVEN, DR. M ELLIOTT, DR J LUCKIT, DR. P RAFFERTY, DR. R DURAIRAJ, PROF. H BASSARIS, PROF. A SKOUTELIS, DR. F VLASTOS,
DR. M TOUBIS, DR. G PANOUTSOPOUL, DR. S APSOKARDOS, DR. D BABALIS, DR. A KARAFOULID, DR. A KATSIVAS, DR. S PATSILINAKOS, PROF. LKS WONG, DR. RSM WONG,
PROF. M BERGOVEC, PROF. M SAMARZIJA, DR. S ZUPANCIC-SALEK DR. S HAJNSEK, DR. A KNEZEVIC, DR. R STEINER, DR. J NIKL, DR. I KONDAKOR, DR. G NYIRATI, DR. G JAKAB,
DR. Z SZAKACS, DR. F NAGY, DR. N SZEGEDI, DR. Z FRANKFURTER, DR. K TAMBUNAN, PROF. HARMANI KALIM, DR. M MACHFØD, DR. D ZELTSER, PROF. S OREN DR. M LISHNER,
PROF. R ZIMLICHMAN, DR. Z STHØGER, DR. H OSAMAH, DR. M ELIAS, PROF T HAYEK, DR. G TELMAN, DR. N ELIAS, DR. S BHAIRAPPA, DR. A CHEVIRI, DR. M GADKARI,
DR. K PRADEEP KUMAR, DR. A NAIK, DR. A OOMMAN, DR. K KUCHIMANCHI, DR. A MAHAJAN, DR. D TALWAR, DR. P GRANT, DR. J WHIG, DR. G AVVARU, DR. RM PL RAMANATHAN,
DR. C RAGHU, PROF. G AGNELLI, DR. W AGENO, DR. M GIORGI PIERFRANCESC, DR. C LODIGIANI, DR. M SILINGARDI, DR. R POGGIO, PROF. S SIRAGUSA, DR. E MORRA,
DR. A DE BLASIO, DR. G CASTAMAN, DR. R BUZZONI, DR. A FONTANELLA, DR. A FALANGA, DR. R LANDOLFI, PROF. M PINI, DR. E DE GAUDENZI, PROF. P PARISE, DR. M BONDI,
DR. M BERRETTINI, PROF. F VIOLI, DR. R QUINTAVALLA, DR. S NISHI, DR. K UTSUGISAWA, DR. T UCHIYAMA, DR. Y MOMIYAMA, DR. K FUKUI, DR. E TANAKA, DR. M NAGAOKA,
DR. T OZAWA, DR. S SAKAGAMI, DR. T TSUJI, DR. N YAMADA, DR. O HATAJI, DR. A WADA, DR. T ICHINOSE, DR. J FUNADA, DR. Y NAKAMURA, DR. S ANDO, DR. K FUJIMOTO,
DR. S MEKARU, DR. K OSHIRO, DR. Y SHIOHIRA, DR. O OKAZAKI, DR. A SHIMIZU, DR. M KATO, DR. H IBATA, DR. S IMAI, DR. H IKEFUJI, DR. T SAITO, DR. K ITO, DR. T MIO,
DR. H KANI, DR. H NAKAGAWA, DR. D-W KANG, DR. C-S CHUNG, DR. B-W YOON, DR. Y-S LEE, DR. D YEUNOH, DR. SM BANG, DR. Y-K KIM, DR. B ALEKNIENE, DR. Z BUTKIENE, DR. R
PETRAUSKIENE, PROF. A BAGDONAS, DR. G GUMBREVICIUS, DR. A VITKAUSKAS, DR. V BASIJOKIENE, DR. S STONKUS, DR. V GRISKEVICIENE, DR. R NORVILIENE, DR. P MULLER,
DR. S RAUH, DR. U KUPCS, DR. V ROZITIS, DR. I STUKENA, DR. D KRIEVINS, DR. N PONTAGA,DR. I AIZSILNIECE, DR. R PEREA SANCHEZ, DR. J GONZALEZ GARZA, DR. M GOMEZ
LARA, DR. J CARDOZA AMADOR, DR. A TANAKA CHAVEZ, DR. V VELASCO RODRIGU, DR. F NARES OCHOA, DR. M VAZQUEZ LOPEZ, DR. C ROMERO LOPE, DR. J GALLEGOS
MARTINEZ, DR. D HERNANDEZ GAETA, DR. M HERVER CABRERA, DR. S PIAW CHIN, DR K HAN SIM, DR. B WAN AHMAD WAN AZMAN, DR. R FIJNHEERD, DR. H CATE, DR. A DEES.
DR. AM KREUK, DR. R TORP, DR. I STOKSTAD, DR. F SCHJESVOLD, DR. W GHANIMA, DR. S JACKSON, DR. D SIMPSON, DR. P OCKELFORD, DR. R COTRINA, DR. M SALAS PEREZ,
DR. V ULLOA PEREZ, DR. Z MONCADA VILELA, DR. F ARRIETA DIAS, DR. O SALAZAR CANDIO, DR. R CASTILLO LEON, DR. Z AZIZ, DR. G UN NABI TAYYAB, DR. N RIZVI, PROF. A
SZCZEKLIK, PROF. L WALASEK, DR. M BOJARSKALOS, PROF. T PASIERSKI, DR M GUTOWSKA-JABLONS, DR. W KRYSIAK, DR. T ZECHOWICZ, PROF. K JAHNZ-ROZYK, DR. E
MIREK-BRYNIARSKA, PROF. M GORSKA, DR. M BIEDRZYCKA, DR. A GOCH, DR M OGOREK, DR. A SYDOR, DR. K WRZESINSKI, DR. F FERREIRA, PROF. L PROVIDENCIA, DR. A
MARTINS, DR. F GOMES, PROF. F SANTOS, PROF. P BETTENCOURT, PROF. J DUCLA SOARES, DR. A MELLO E SILVA, DR. T RODRIGUES, DR. A FERREIRA, DR. S KHATKOVA, DR A
SOTNIKOV, PROF. T FEDOROVA, PROF. G AROUTYNOV, PROF. M GLEZER, PROF. VN MOISEEV, DR. N SHILKINA, DR. O ERSHOVA, DR. P SVENSSON, DR. I TORSTENSSON, DR. A
SJAELANDER, DR. J OSTERGREN, DR. I TIMBERG, DR A-C LASKA, DR. PG WIKLUND, DR. E BERTHOLDS, DR. M CWIKIEL, DR. T HOW ONG, DR. R TAN, DR. A NG, DR. G CHUA, DR H
WOOI GAN, PROF. O TENG TANG, DR. M JEREB, DR. B ZVAN, DR. M FLEZAR, DR. G TRATAR, DR. ML SOK, DR. V GORJUP, DR. L GASPAR, DR. J STEVLIK, DR. V SPISAK, DR. F
KOVAR, DR. M SZENTIVANYI, PROF. C PERMPIKUL, DR. A WATTANATHUM, DR. C POTHIRAT, PROF. S KUCUKOGLU, PROF. B ILERIGELEN, PROF. E GOKER, PROF. H SIRIN, PROF.
U YILMAZ, PROF. S NALBANTGIL, DR. Y-H LIN, DR. B-F GUO, DR. C-L HAN, DR. K-G SHYU, DR. K YIN-CHING CHUANG, DR. V SKREBKOV, PROF. V SORKIN, PROF. Y SVYSHCHENKO,
PROF. O KORZH, PROF. S GENYK, PROF. L VORONKOV, DR. V TSELUYKO, DR. O KARPENKO, PROF. I VAKALIUK, DR. M PEREPELIUK, PROF. O LEGKONOGOV, DR. V KOVAL, DR. A
POLYAKOV, DR. Y GONCHAROVA, DR. T RYABICHENKO, PROF. M VATUTIN, DR. A HEYDER, DR. R MURRAY, DR. P RASTOGI, DR. M PLAUTZ, DR. R YUSEN, DR. R LAVENDER, DR. G
MERLI, DR. A JAFFER, DR. P MEHRA, DR. G JOHNSON, DR. P MANOS, DR. S KAATZ, DR. V NADAR, DR. T WUN, DR. J MASSON, DR. R LERNER, DR. A SEIBERT, DR. R MCLAFFERTY,
DR. J WELKER, DR. P WRIGHT JR., DR. K RAJAMANI, DR. D SCHULLER, DR. A SHARMA, DR. J SIMMONS, DR. F WHITTIER, DR. J WARD, DR. N DABOUL, DR. S CHASTAIN, DR. J
DEXTER, DR. J UPDEGROVE, DR. W REITER, DR. S STOLTZ, DR. S CONRAD, DR. M HAZELRIGG, DR. T LING, DR. D CHEN, DR. K MAYNOR, DR. W FRENCH, DR. D DIETRICH, DR. C
LAWTON, DR. J BRENSILVER, DR. B HELLER, DR. C ALBRECHT III, DR. C COWLEY, DR. S MAHAL, DR. S ANDERSON, DR. W TØ, DR. P POKHAREL, DR. M FONTES,
DR. H MINKOWITZ, DR. M CONCHA, DR. R STEIN, DR. M PEBERDY, DR. T BIRCH, DR. R LIGHT, DR. G SOFF, DR. M COX, DR. A NATHANSON, DR. R FEI, DR. J REYES, DR. M KAZIMIR,
DR. D WILLIAMS, DR. T ZIEDALSKI, DR. G HILL JR, DR. J SUEN, DR. C GREENBERG, DR. P MEHTA, DR. K WAXMAN, DR. W PATTON, DR. A COMEROTA, DR. C THURM, DR. E
GONZALES, DR. P JETTY, DR. M BENNINGHOFF, DR. M BIDAIR, DR. O QUINTANA, DR. D ADLER, PROF. L DREOSTI, DR. JOHAN ENGELBRECHT, DR. C KØGELENBERG, DR B
RAPOPORT, DR. A ROODT, DR. C SMITH, DR. F STEENKAMP, DR. R SOMMERS, DR. H JANSE VAN RENSBURG, DR. B BLOY, DR. H NORTJE, DR. W RABIE, DR. E VAN
NIEUWENHUIZEN, DR. L VAN ZYL

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