8 research outputs found
Cross-reactivity between terrestrial snails (Helix species) and house-dust mite (Dermatophagoides pteronyssinus). II. In vitro study
- Author
- Publication venue
- 'Wiley'
- Publication date
- Field of study
Combining clinicopathological predictors and molecular biomarkers in the oncogenic K-RAS/Ki67/HIF-1α pathway to predict survival in resectable pancreatic cancer
- Author
- A H Tang
- A Maitra
- AU Ahmed
- B Lebe
- B Vogelstein
- CL Sawyers
- CL Wolfgang
- CM Ardito
- DD Von Hoff
- E Costello
- F Guillaumond
- G M Petersen
- GL Semenza
- H Zhong
- JM Winter
- JS Sebolt-Leopold
- JW Valle
- KJ Stanton
- M Hidalgo
- MH Katz
- MM Javle
- N Akakura
- N R Reed
- PJ Heagerty
- Q Chang
- R L Schmidt
- R Qin
- R Siegel
- RH Hruban
- RL Schmidt
- S T Chari
- T C Smyrk
- T Conroy
- T Kitada
- T Schnelldorfer
- T Shibaji
- TA Sohn
- TR Spivak-Kroizman
- WR Wilson
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- Field of study
The effect of rebound exercise and treadmill walking on the quality of life for patients with non-insulin-dependent type 2 diabetes
- Author
- AA Motala
- AE Carter
- AH Al-Shehri
- AL Dunn
- AM Jacobson
- AM Kriska
- AM Stys
- American Diabetes Association
- American Thoracic Society
- C Jenkinson
- EL González
- G Roglic
- J Hahl
- J Jensen
- JC Chan
- Jibril M. Nuhu
- JN Myers
- KJ McInnis
- M Javanbakht
- M Walker
- MA Testa
- ME Maruish
- MI Harris
- MJ Karvonen
- MM Engelgau
- NG Boule
- NJ Fortuin
- P Zimmet
- PO Lim
- R Kisan
- R KlevsgĂĄrd
- R Rubin
- RD Reid
- RR Rubin
- S Colagiuri
- S Wild
- Sonill S. Maharaj
- SQ Ardito
- SR Colberg
- SS Shapiro
- TA Bauer
- TW Rowland
- V Joshi
- WH Polonsky
- WH Polonsky
- WR Sukala
- WT Garvey
- Y Nakawatase
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- Field of study
Surgical Management of Hepatocellular Adenoma: Take It or Leave It?
- Author
- A Koffron
- A Weimann
- B Descottes
- B Descottes
- BF Flowers
- C Toso
- CH Hung
- CK Charny
- D Cherqui
- D Erdogan
- D Mathieu
- David A. Geller
- DJ Windt Van der
- DM Nagorney
- EK Paulson
- Erin R. Ochoa
- F Ardito
- FC Cobey
- G Ault
- H BĂĽhler
- H Tesluk
- HA Edmondson
- J Belghiti
- J Closset
- J Kim
- J Neuberger
- J. Wallis Marsh
- JA Ameriks
- Jason T. Heckman
- JB Rooks
- Jennifer Steel
- JH Foster
- JH Gold
- KR Reddy
- KY Chung
- L Arrive
- L Barthelmes
- L Carlis De
- L Grazioli
- L Wilkens
- LC Tao
- M Golli
- N Katkhouda
- P Aseni
- P Bioulac-Sage
- P Herman
- P Kerlin
- P Labrune
- P Marini
- PH Anderson
- R Weil 3rd
- S Rebouissou
- SC Gordon
- Shane E. Holloway
- SK Reddy
- Sung W. Cho
- T Ichikawa
- T Leese
- T Terkivatan
- T Terkivatan
- T. Clark Gamblin
- TD Atwell
- UP Steinbrecher
- V Paradis
- WH Marks
- WL Ramseur
- WR Jarnagin
- YW Chen
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- Field of study
RAS-targeted therapies: is the undruggable drugged?
- Author
- A Chaikuad
- A Chandra
- A Cruz-Migoni
- A Ho
- A Nakamura
- A Patgiri
- A Patnaik
- A Ribas
- A Rittmeyer
- A Varga
- A Yang
- AD Cox
- AG Robertson
- AJ Laude
- AM Bennett
- AM Eggermont
- AM Winter-Vann
- AN Shoushtari
- AP Algazi
- AW Tolcher
- AW Tolcher
- B Kruspig
- B Vanhaesebroeck
- BA Boone
- BA Frederick
- BB Friday
- BM Wolpin
- C Ambrogio
- C Lebbe
- C Mao
- C Navas
- C Robert
- C Robert
- C Sun
- CA Carter
- CA Pratilas
- Cancer Genome Atlas Network
- Cancer Genome Atlas Network
- Cancer Genome Atlas Network
- Cancer Genome Atlas Network
- Cancer Genome Atlas Network
- CD Weekes
- CE Burd
- CE Quevedo
- CG Kinsey
- CM Ardito
- CM Emery
- CM Johannessen
- CS Karapetis
- D Abankwa
- D Juric
- D Kessler
- D Lake
- D Rabara
- DA Fruman
- DA Ruess
- DB Johnson
- DB Whyte
- DH Palmer
- DM Houslay
- DM Owens
- DR Gentile
- DS Chen
- DT Le
- DT Le
- E Hirsch
- E Segelov
- E Tran
- E Vakana
- E Van Cutsem
- E Van Cutsem
- EB Garon
- EJ Morris
- EL Leung
- EM O’Reilly
- EM Van Allen
- EM Van Allen
- ES Leshchiner
- F Burrows
- F Janku
- F Skoulidis
- F Su
- FD Tsai
- FS Hodi
- G Bodoky
- G Hatzivassiliou
- G Hatzivassiliou
- G Hatzivassiliou
- G Richard
- G Zimmermann
- GF Xu
- GG Jones
- GI Shapiro
- GR Blumenschein Jr.
- H Ebi
- H Linardou
- H Lu
- HA Yu
- HJ Kim
- HP Moll
- HY Chen
- I Khan
- I Mohammed
- I Yen
- IA Prior
- J Bean
- J Bennouna
- J Brahmer
- J Canon
- J Caramel
- J Guldenhaupt
- J Hallin
- J Li
- J Villanueva
- J Weber
- JA Engelman
- JA Engelman
- JC Hunter
- JD Hainsworth
- JD Wolchok
- JJ Winter
- JM Eatrides
- JM Mason
- JM Ostrem
- JO Ebinu
- JP McGrath
- JR Veatch
- JS Weber
- JY Xue
- K Inouye
- K Lou
- K Nakamura
- K-A Monaco
- KA Manu
- KA Rauen
- KL Bryant
- KM Haigis
- KP Hoeflich
- KT Flaherty
- L Bonfini
- L Johnson
- L Kessler
- L Zimmer
- LA Garraway
- LB Alexandrov
- LC Young
- LDJ Buday
- LV Sequist
- M Aoki
- M Dance
- M Drosten
- M Drosten
- M Gehringer
- M Mao
- M Merchant
- M Mita
- M Molina-Arcas
- M Molina-Arcas
- M Okaniwa
- M Peeters
- M Reck
- M Sanclemente
- M Solman
- M Tartaglia
- M Wang
- MA Coelho
- MA Socinski
- MC Burns
- MC Schmid
- MD Hellmann
- MD Hellmann
- ME Dudley
- ME Welsch
- MJ Moore
- MJ Overman
- MK Dougherty
- MK Gjertsen
- MMF Trahey
- MP Patricelli
- MR Janes
- MT Blasco
- MT Mazhab-Jafari
- N Potenza
- NI Marin-Ramos
- NJ White
- P Castel
- P Dent
- P Lito
- P Lito
- P Prakash
- PA Ascierto
- PA Janne
- PA Schwartz
- PF Robbins
- PF Robbins
- PI Poulikakos
- PJR Ebert
- PL Bedard
- Q Sun
- Q Wang
- QJ Wang
- R Nazarian
- R Spencer-Smith
- R Sulahian
- R Yaeger
- RC Hillig
- RE Royal
- RG Amado
- RH Vonderheide
- RJ Nichols
- RJ Sullivan
- RJ Sullivan
- RJ Sullivan
- RS Herbst
- S Kobayashi
- S Misale
- S Muratcioglu
- S Pant
- S Pells
- S Sarkar-Banerjee
- S Thomson
- S Wee
- S Yang
- SB Boga
- SB Peng
- SE Hampton
- SJ Antonia
- SJ Moschos
- SJ Plowman
- SJ Plowman
- SJ Plowman
- SJ Ross
- SL Topalian
- SR Whittaker
- SV Bhagwat
- SV Sharma
- T Golan
- T Maurer
- T Tian
- T Wang
- TE Keenan
- The AACR Project GENIE Consortium
- TW Kim
- U Keilholz
- W De Roock
- W Li
- W Pao
- W Zou
- WC Lin
- WR Judd
- X Nan
- X Wang
- Y He
- Y Samuels
- Y Sun
- Y Xie
- Y Zhou
- YM Yao
- YN Chen
- Z Fang
- Z Karoulia
- ZQ Shi
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 15/08/2020
- Field of study
RAS (KRAS, NRAS and HRAS) is the most frequently mutated gene family in cancers, and, consequently, investigators have sought an effective RAS inhibitor for more than three decades. Even 10 years ago, RAS inhibitors were so elusive that RAS was termed 'undruggable'. Now, with the success of allele-specific covalent inhibitors against the most frequently mutated version of RAS in non-small-cell lung cancer, KRASG12C, we have the opportunity to evaluate the best therapeutic strategies to treat RAS-driven cancers. Mutation-specific biochemical properties, as well as the tissue of origin, are likely to affect the effectiveness of such treatments. Currently, direct inhibition of mutant RAS through allele-specific inhibitors provides the best therapeutic approach. Therapies that target RAS-activating pathways or RAS effector pathways could be combined with these direct RAS inhibitors, immune checkpoint inhibitors or T cell-targeting approaches to treat RAS-mutant tumours. Here we review recent advances in therapies that target mutant RAS proteins and discuss the future challenges of these therapies, including combination strategies
Packaging
- Author
- A Asada
- A Burkitt
- A Clark
- A Drift van der
- A Gangulee
- A Gayet
- A Jongeans
- A Kager
- A Kusy
- A Nyblom
- A Pfahnl
- A Pfahnl
- A Salmela
- A Shimazaki
- A Sjogren
- A Snopek
- A Socolovsky
- A Socolovsky
- A Socolovsky
- A Socolovsky
- A Tamura
- A Verbokken
- AA Appen
- AA Bilotti
- AA Bokrinskaya
- AA Friesem
- AA Kaposi
- AA Khalilov
- AA Rifkin
- AA Rossoshinskii
- AB Blushinskii
- AB Crawford
- AC Watson
- AD Andrade
- AD Close
- AE Ruehli
- AE Ruehli
- AE Ruehli
- AF Dyson
- AF Schmeckenbecher
- AF Schmeckenbecher
- AG Bennett
- AG Cozens
- AG Dentai
- AG Kokkas
- AH Agajanian
- AH Johnson
- AI Tamburrino
- AJ Pikor
- AJ Streb
- AJ Streb
- AL Medesha
- AM Manolescu
- AM Stommel
- AN Luce Jr.
- Anon.
- Anon.
- AP Kemeny
- AP Turley
- AP Youmans
- AR Gerhard
- AR Hart
- AR Macdonaid
- AR Owens
- AS Shah
- AT English
- AV Fraioli
- AV Grimm
- AW Henderson
- AW Postlehwaite
- AW Scott
- AY Chen
- B Bianco
- B Britton
- B Chew
- B Coker
- B Diel
- B Harrison
- B Mazurek
- B Miladinovic
- B Piwczyk
- B Reich
- B Reich
- B Reich
- B Shelpuk
- B Wedzicha
- B Williams
- B Wozniakowski
- B Wurst
- BB Iperen van
- BC Fetcher
- BC Roberts
- BC Rogers
- BD Platonov
- BE Sear
- BH Cranston
- BJ Parker
- BJ Sealy
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- BL Weiss
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- CG Schoppe
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- D Abenaim
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- H Lobl
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- KO Leedy
- L Altman
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- L Parham
- L Pittroff
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- L Sztankovics
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- LD Howe Jr.
- LF Miller
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- LJ Eckert
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- LM Spandorfer
- LR Greenman
- LS Buchoff
- LS Goldman
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- LT Browne
- LV Gregor
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- LW Brown
- LW Condra
- M Cabezas
- M Caughey
- M Cichetti
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- M Kashiwabara
- M Koltai
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- M Lazar
- M Mika
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- M Riel
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- P Abley
- P Balakrishma
- P Becker
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- S Stephen
- S Yoshimura
- SA Abbas
- SB Marshall
- SC Bawa
- SE Grossman
- SE Grossman
- SE Grossman
- SE Scrupski
- SE Scrupski
- SE Scrupski
- SE Scrupski
- SE Scrupski
- SI Bruder
- SJ Feltham
- SJ Stein
- SL Hurst
- SM Roback
- T Balmer
- T Coats
- T Hayasaka
- T Ihochi
- T Kamo
- T Mann
- T Mizusawa
- T Okabe
- T Okabe
- T Suzuki
- T Yanagisawa
- TA Hooke
- TA Wiley
- TB Gillis
- TC Reissing
- TE Brady
- TH Briggs
- TH Chang
- TH Ramsey
- TH Ramsey
- TH Ramsey
- TH Ramsey Jr.
- TJ Dowling
- TJ Faith Jr.
- TJ Matcovich
- TL Bittner
- TM Foster
- TT Hitch
- UC Paek
- V Doetsch
- V Ghergia
- V Platter
- V Stoicheva
- VC Marcotte
- VI ValDman
- VT Guntlow
- W Aung
- W Aung
- W Bantz
- W Bielawski
- W Buhler
- W Dollt
- W Eberhardt
- W Gerling
- W Kleber
- W Kovel
- W Maslankiewicz
- W Pletscher
- W Roman
- W Schoberl
- W Spathling
- W Ulmer
- W Westfall
- W Worotinski
- W Wuich
- WA Brantley
- WA Edel
- WB Hugle
- WB Joyce
- WB Pennebaker
- WC Miller
- WC Mow
- WD Bascom
- WE Blodgett
- WE Donath
- WE Loeb
- WE Simpson
- WE Wilson
- WF Finch
- WG Ashman
- WG Dryden
- WH Chang
- WH Class
- WH Legat
- WL Clough
- WM Flock
- WN Bolster
- WR DeBoskey
- WR Swiss
- WS Meadows
- WS Routh
- WT Chen
- Y Kubota
- Y Kunihiro
- Y Nagai
- Y Taketa
- Y Taketa
- Y Taketa
- Y Taketa
- YMF Marikar
- YP Ermolaev
- YP Yermolaev
- Z Czechowska
- Z Illyefalvi Vitez
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 01/01/1976
- Field of study
Evolocumab and clinical outcomes in patients with cardiovascular disease
- Author
- Abelson M
- Aboufakher R
- Abrahamsen Te
- Accini Mendoza Jl
- Acheatel R
- Ackermann D
- Adamkova V
- Adams M
- Adlam D
- Aggarwal R
- Aggarwal S
- Ahsan A
- Ainsworth P
- Airody Govinda R
- Akai A
- Ako J
- Al-Bahrani A
- Al-Joundi T
- Aldegather J
- Aldrete Velasco Ja
- Alfieri A
- Alt I
- Alzohaili O
- Amerena J
- Amin J
- Amoedo R
- Amuchastegui M
- Anderson T
- Andreka P
- Andreotti F
- Angoulvant D
- Ansell B
- Antalik L
- Antkowiak-Piatyszek K
- Appel K
- Arakawa T
- Arana Londoño C
- Ardissino D
- Ardito Wr
- Arkhipov M
- Arsenescu-Georgescu C
- Asamoah N
- Ascaso Gimilio Jf
- Atar S
- Atassi K
- Athyros V
- Auerbach E
- Awtry E
- Baass A
- Badariene J
- Badat A
- Badila E
- Bae J
- Baigent C
- Bain S
- Baird I
- Baker J
- Balbay Y
- Baldari D
- Ballantyne C
- Bammert A
- Banach M
- Bandh S
- Banerjee S
- Banik M
- Banikova A
- Barbarash O
- Barcinas R
- Barnum O
- Barroso de Souza Wk
- Bart B
- Barton J
- Bata I
- Batalla E
- Bayat J
- Bazzoni Ruiz Ae
- Bednarkiewicz Z
- Beer Hj
- Begg A
- Beltrame J
- Bendermacher P
- Benton R
- Berger C
- Bergeron J
- Bergler-Klein J
- Berglund S
- Berlacher P
- Bernstein M
- Bertolet B
- Bertolim Precoma D
- Bhagwat R
- Bhargava R
- Bhushan R
- Biasucci Lm
- Bilianou H
- Blagden M
- Blaha V
- Blasko P
- Blicharski T
- Blignaut S
- Blokhin A
- Blumberg E
- Bodanese Lc
- Bokern M
- Bolshakova O
- Bonaca Mp
- Bonnet B
- Bosiljanoff P
- Boswijk D
- Botero Lopez R
- Bourhaial H
- Bousboulas S
- Brabec T
- Brezina B
- Bronnum-Schou J
- Brotanek J
- Broughton R
- Brown C
- Brown Wv
- Bubnova M
- Budoff M
- Burgess L
- Burianova H
- Burrough B
- Butler R
- Buysschaert I
- Bystryk L
- Capps N
- Cappuccio F
- Cardona Muñoz Eg
- Carhart R
- Cariou B
- Carr K
- Case C
- Castellanos Bueno R
- Catez E
- Caulfield M
- Cayla G
- Cech V
- Cepelak M
- Ceska R
- Cha J
- Chandra L
- Chapman K
- Charlier F
- Charng Mj
- Charvat J
- Chauhan A
- Cheek Hb
- Chehayeb R
- Chen J
- Chen X
- Chen Y
- Chenu P
- Cheung D
- Cho Y
- Choi D
- Chopra Vk
- Chorin E
- Christensen T
- Christofides E
- Cifkova R
- Civeira Murillo F
- Cizinsky S
- Clardy D
- Claxton E
- Clements B
- Cobos Jl
- Coching Rm
- Coetzer Tf
- Coisne D
- Collins J
- Colombo H
- Coman I
- Conejeros Kindel C
- Connolly D
- Constance C
- Contzen C
- Cordero Fort A
- Cornel Jh
- Coronel Arroyo Ja
- Cosmi F
- Cottin Y
- Cox N
- Crater T
- Crean P
- Croce K
- Cross D
- Crowley D
- Cruickshank K
- Cuadrado Ja
- Cui H
- Cui Y
- Cummings M
- Cuneo C
- Cunha Borges Jl
- Cure Cure Ca
- Cygler J
- Dabrowska M
- Dabrowski M
- Dahlén G
- Dai H
- Dan Ga
- Danias P
- Darius H
- Dauber I
- Dave K
- Davila W
- Davis Br
- Davis G
- Davis M
- Dawood S
- de Belder M
- De Caterina R
- De Ferrari Gm
- De Jong Dm
- De La Cruz A
- De la Peña Topete Gdj
- De los Rios Ibarra Mo
- De Meulemeester M
- De Nooijer C
- De Raedt H
- de Sa Cunha R
- De Souza J
- Dear H
- Deedwania Pc
- Delarche N
- Delgado E
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- Den Hartog F
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- Desai A
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- Desire A
- Dill S
- Diogo J
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- Dobkin L
- Dobratz D
- Donnelly P
- Douglas F
- Dowell A
- Doyle T
- Dronov D
- du Toit M
- Du Y
- Duarte Barbosa Ec
- Dubaniewicz W
- Duchesne L
- Dunaj M
- Dunbar R
- Durlach V
- Dutra O
- Duzenli M
- Dwivedi Sk
- Dyke C
- Dzupina A
- Earl J
- Eaton C
- Ebenbichler C
- Eberli F
- Ebrahim I
- Edes I
- Eglite R
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- El Shahawy M
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- Elbl L
- Eliaschewitz Fg
- Elisaf M
- Ellery A
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- Erickson B
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- Estepar Ra
- Ezhov Mv
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- Fairlie H
- Falck G
- Fan Kyy
- Farhat N
- Farris N
- Farshid A
- Fedele Francesco
- Fernandes Manenti Er
- Fernandez S
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- Ferreira J
- Ferri C
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- Filipová S
- Finlayson J
- Fiore G
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- Fiserova N
- Fishbein G
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- Focil A
- Forgosh L
- Fortuin F
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- Fox C
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- Freidlin M
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- Friart A
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- Funazaki T
- Gabra N
- Gaciong Za
- Gan Hw
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- Gao X
- Garbocz P
- Garrahy P
- Gaudet D
- Gaunt R
- Gavish D
- Ge Z
- Geadah C
- Gelfand E
- Georgiev Bg
- Germar A
- Ghali J
- Gilpatrick M
- Giugliano G
- Giugliano Robert P.
- Glenny Ja
- Go A
- Go Y
- Goel A
- Goldenberg E
- Goloshchekin B
- Golovchenko O
- Gonnelli S
- Gonsorcik J
- Gonzalez Juanatey Jr
- Gonzalez-Galvez G
- Goralski M
- Gordeev I
- Gorog D
- Gossard D
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- Gotchev D
- Gouni-Berthold I
- Graham J
- Greenwald J
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- Grubb S
- Gruberg L
- Grzegorzewski B
- Gu Y
- Gupta D
- Gupta M
- Gustiene O
- Guyton J
- Guzik T
- Gyrina O
- Habaluyas R
- Hack T
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- Hage Korban E
- Hajko E
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- Hall A
- Halperin F
- Hamet P
- Hammett C
- Hamroff G
- Han Kh
- Handelsman Y
- Hanefeld M
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- Hanusch U
- Hare Po
- Harris M
- Hart R
- Hartleib M
- Harvey J
- Hasbani Eg
- Hasin Y
- Hata Y
- Hatalova K
- Hatharasinghe R
- Haught Wh
- He Y
- Hearne S
- Heller S
- Henderson D
- Henein S
- Hengstenberg C
- Hennekens Ch
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- Herczeg B
- Herman L
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- Hersbach F
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- Hershson A
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- Higashi Y
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- Hornyik A
- Horrigan M
- Hosokawa S
- Hove J
- Hovland A
- Hoye A
- Hrabar A
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- Hsia C
- Hsieh I
- Hsieh Y
- Huang C
- Huang H
- Huang W
- Huber K
- Huling R
- Hulinsky V
- Huynh T
- Hysing J
- Ibrahim H
- Iida H
- Ilkowski J
- Illescas Diaz Jj
- Im K
- Inage T
- Inoko M
- Isermann B
- Issa B
- Issa M
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- Iteld B
- Ivan P
- Iwade K
- Izar Mc
- Izumiya Y
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- Jain A
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- Jasinkevica I
- Jehle A
- Jelinek P
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- Jeong M
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- Jerabek O
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- Jocson G
- Joffe I
- Johansson P
- Johnston J
- Joshi A
- Juang J
- Juergens C
- Jukema Jw
- Jupp B
- Kadokami T
- Kahri J
- Kahrmann G
- Kaigawa K
- Kaik J
- Kajiyama S
- Kakurina N
- Kanevsky E
- Kania G
- Kanno M
- Kapp C
- Karadi I
- Karakas M
- Karalis I
- Karen I
- Karpenko O
- Kashyap M
- Kassner U
- Kast P
- Katsuda Y
- Kawabata K
- Kawamitsu K
- Kawasaki T
- Kayikcioglu L
- Kazdera P
- Keech Anthony C.
- Keeling P
- Kellnerova I
- Kereiakes D
- Kerr Saraiva Jf
- Khalife K
- Khan A
- Khan B
- Khan M
- Khandait V
- Khanoyan P
- Khurana S
- Kim B
- Kim M
- Kim S
- Kim W
- Kinasz L
- King M
- Kingston D
- Kinova E
- Kirma C
- Kirstein J
- Kiss R
- Kitova L
- Kiyosue A
- Kjaernli T
- Kjaerulf Jensen H
- Klausen Ic
- Klimsa Z
- Klug E
- Klutstein M
- Knusel B
- Kobalava Z
- Kochiadakis G
- Koga Y
- Kohli N
- Koike A
- Kok J
- Koleckar P
- Kolovou G
- Kondagunta V
- Konieczny M
- Kooij A
- Kopaczewski J
- Kopytsya M
- Koren M
- Kork A
- Korsgaard Thomsen K
- Korzh O
- Kosek Z
- Kosior D
- Kostenko V
- Kostner K
- Kothiwale V
- Kovar F
- Kozlowski L
- Kozuma K
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- Kracoff O
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- Kraydashenko O
- KraŃ–z I
- Krejcova H
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- Kubica J
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- Ladyjanskaia G
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- Landzberg J
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- Norheim P
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- Oku K
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- Orourke D
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- Youngman D
- Younis L
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- Zabowka M
- Zahn L
- Zamorano Gomez Jl
- Zarich S
- Zateyshchikov D
- Zdrenghea D
- Zechowicz T
- Zeig S
- Zemanek J
- Zeng X
- Zhang L
- Zhang X
- Zhao S
- Zheng Y
- Zheng Z
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- Zhurba S
- Zidkova E
- Zieba B
- Ziegler O
- Zilahi Z
- Zrazhevskiy K
- Ă–stergren J
- Publication venue
- 'Massachusetts Medical Society'
- Publication date
- 01/01/2017
- Field of study
BACKGROUND Evolocumab is a monoclonal antibody that inhibits proprotein convertase subtilisin-kexin type 9 (PCSK9) and lowers low-density lipoprotein (LDL) cholesterol levels by approximately 60%. Whether it prevents cardiovascular events is uncertain. METHODS We conducted a randomized, double-blind, placebo-controlled trial involving 27,564 patients with atherosclerotic cardiovascular disease and LDL cholesterol levels of 70 mg per deciliter (1.8 mmol per liter) or higher who were receiving statin therapy. Patients were randomly assigned to receive evolocumab (either 140 mg every 2 weeks or 420 mg monthly) or matching placebo as subcutaneous injections. The primary efficacy end point was the composite of cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization. The key secondary efficacy end point was the composite of cardiovascular death, myocardial infarction, or stroke. The median duration of follow-up was 2.2 years. RESULTS At 48 weeks, the least-squares mean percentage reduction in LDL cholesterol levels with evolocumab, as compared with placebo, was 59%, from a median baseline value of 92 mg per deciliter (2.4 mmol per liter) to 30 mg per deciliter (0.78 mmol per liter) (P<0.001). Relative to placebo, evolocumab treatment significantly reduced the risk of the primary end point (1344 patients [9.8%] vs. 1563 patients [11.3%]; hazard ratio, 0.85; 95% confidence interval [CI], 0.79 to 0.92; P<0.001) and the key secondary end point (816 [5.9%] vs. 1013 [7.4%]; hazard ratio, 0.80; 95% CI, 0.73 to 0.88; P<0.001). The results were consistent across key subgroups, including the subgroup of patients in the lowest quartile for baseline LDL cholesterol levels (median, 74 mg per deciliter [1.9 mmol per liter]). There was no significant difference between the study groups with regard to adverse events (including new-onset diabetes and neurocognitive events), with the exception of injection-site reactions, which were more common with evolocumab (2.1% vs. 1.6%). CONCLUSIONS In our trial, inhibition of PCSK9 with evolocumab on a background of statin therapy lowered LDL cholesterol levels to a median of 30 mg per deciliter (0.78 mmol per liter) and reduced the risk of cardiovascular events. These findings show that patients with atherosclerotic cardiovascular disease benefit from lowering of LDL cholesterol levels below current targets
Ezetimibe added to statin therapy after acute coronary syndromes
- Author
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- Aambakk MB
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- Tarastchuk JC
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- Ă…ngman K
- Édes I
- Ă–stberg S
- Publication venue
- 'Massachusetts Medical Society'
- Publication date
- 01/01/2015
- Field of study
BACKGROUND: Statin therapy reduces low-density lipoprotein (LDL) cholesterol levels and the risk of cardiovascular events, but whether the addition of ezetimibe, a nonstatin drug that reduces intestinal cholesterol absorption, can reduce the rate of cardiovascular events further is not known. METHODS: We conducted a double-blind, randomized trial involving 18,144 patients who had been hospitalized for an acute coronary syndrome within the preceding 10 days and had LDL cholesterol levels of 50 to 100 mg per deciliter (1.3 to 2.6 mmol per liter) if they were receiving lipid-lowering therapy or 50 to 125 mg per deciliter (1.3 to 3.2 mmol per liter) if they were not receiving lipid-lowering therapy. The combination of simvastatin (40 mg) and ezetimibe (10 mg) (simvastatin-ezetimibe) was compared with simvastatin (40 mg) and placebo (simvastatin monotherapy). The primary end point was a composite of cardiovascular death, nonfatal myocardial infarction, unstable angina requiring rehospitalization, coronary revascularization ( 6530 days after randomization), or nonfatal stroke. The median follow-up was 6 years. RESULTS: The median time-weighted average LDL cholesterol level during the study was 53.7 mg per deciliter (1.4 mmol per liter) in the simvastatin-ezetimibe group, as compared with 69.5 mg per deciliter (1.8 mmol per liter) in the simvastatin-monotherapy group (P<0.001). The Kaplan-Meier event rate for the primary end point at 7 years was 32.7% in the simvastatin-ezetimibe group, as compared with 34.7% in the simvastatin-monotherapy group (absolute risk difference, 2.0 percentage points; hazard ratio, 0.936; 95% confidence interval, 0.89 to 0.99; P = 0.016). Rates of pre-specified muscle, gallbladder, and hepatic adverse effects and cancer were similar in the two groups. CONCLUSIONS: When added to statin therapy, ezetimibe resulted in incremental lowering of LDL cholesterol levels and improved cardiovascular outcomes. Moreover, lowering LDL cholesterol to levels below previous targets provided additional benefit