7 research outputs found
Chromatin loop anchors are associated with genome instability in cancer and recombination hotspots in the germline
- Author
- A Auton
- A Canela
- A Gardini
- A Liaw
- A Losada
- AL Valton
- AR Quinlan
- AS Kudlicki
- B Charlesworth
- B Gel
- B Schuster-Bockler
- BJ Taylor
- BL Moore
- C Bertoli
- C Grey
- CE Grant
- CJ Lord
- CM Carvalho
- CM Manville
- Colin A. Semple
- CS Walsh
- CT Ong
- CY McLean
- D Hnisz
- D Perera
- DG Lupianez
- DR Zerbino
- E Guillou
- E Hatchi
- E Splinter
- Encode Project Consortium
- EP Nora
- F Baudat
- F McNicoll
- F Pratto
- G Coop
- G Fudenberg
- G Fudenberg
- G McVicker
- GA McVean
- J Feichtinger
- J MacArthur
- J Weischenfeldt
- JA Rosenfeld
- JA Stamatoyannopoulos
- JHI Haarhuis
- JM Engreitz
- JN Strathern
- JR Dixon
- JS Gehring
- K Brick
- K Hilmi
- L Uuskula-Reimand
- LJ Valentijn
- M Peifer
- MA Reijns
- MH Nichols
- PA Northcott
- R Hänsel-Hertsch
- R Katainen
- R Sabarinathan
- S Besenbacher
- S Courbet
- S Groschel
- S Morganella
- S Myers
- S Myers
- S Nik-Zainal
- SS Rao
- SV Lensing
- TJ Hudson
- TL Bailey
- TW Glover
- TW Glover
- V Dileep
- VB Kaiser
- Vera B. Kaiser
- W Winckler
- WA Flavahan
- WM Hicks
- Y Drier
- Y Liu
- Y Zhang
- Z Tang
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 01/07/2018
- Field of study
Abstract Background Chromatin loops form a basic unit of interphase nuclear organization, with chromatin loop anchor points providing contacts between regulatory regions and promoters. However, the mutational landscape at these anchor points remains under-studied. Here, we describe the unusual patterns of somatic mutations and germline variation associated with loop anchor points and explore the underlying features influencing these patterns. Results Analyses of whole genome sequencing datasets reveal that anchor points are strongly depleted for single nucleotide variants (SNVs) in tumours. Despite low SNV rates in their genomic neighbourhood, anchor points emerge as sites of evolutionary innovation, showing enrichment for structural variant (SV) breakpoints and a peak of SNVs at focal CTCF sites within the anchor points. Both CTCF-bound and non-CTCF anchor points harbour an excess of SV breakpoints in multiple tumour types and are prone to double-strand breaks in cell lines. Common fragile sites, which are hotspots for genome instability, also show elevated numbers of intersecting loop anchor points. Recurrently disrupted anchor points are enriched for genes with functions in cell cycle transitions and regions associated with predisposition to cancer. We also discover a novel class of CTCF-bound anchor points which overlap meiotic recombination hotspots and are enriched for the core PRDM9 binding motif, suggesting that the anchor points have been foci for diversity generated during recent human evolution. Conclusions We suggest that the unusual chromatin environment at loop anchor points underlies the elevated rates of variation observed, marking them as sites of regulatory importance but also genomic fragility
Extension and Folding of Nascent Peptides on Ribosomes
- Author
- A Yonath
- AS Spirin
- AS Spirin
- AS Spirin
- B Hardesty
- B Hardesty
- C Bemabeu
- D Moazed
- FM Richards
- G Blobel
- H Chantrenne
- H Noll
- H-J Rheinberger
- HF Noller
- HF Noller
- J Gooch
- J Watson
- JA Mendoza
- LA Ryabova
- LI Malkin
- LS Victorova
- NB Tarussova
- OW Odom
- OW Odom
- OW Odom
- PY Chou
- R Hartman
- R Lill
- S Atherton
- S Fahnestock
- TE Creighton
- VA Kolb
- W Kudlicki
- WD Picking
- WD Picking
- WL Picking
- WL Picking
- WM Jou
- WP Smith
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 01/01/1993
- Field of study
i-BLESS is an ultra-sensitive method for detection of DNA double-strand breaks
- Author
- A Canela
- A Guedin
- A Mehta
- A Mitra
- A Piazza
- A Piazza
- A Varizhuk
- AS Kudlicki
- BA Evert
- C Richardson
- CL White
- D Botstein
- D Rhodes
- DE Bassett Jr
- EA Hoffman
- EP Mimitou
- J Overhauser
- JM Cherry
- K Paeschke
- KD Mills
- KW Yuen
- L Colleaux
- L Miller-Fleming
- LH Hartwell
- LM Petek
- M Lisby
- MM Vilenchik
- N Crosetto
- R Rodriguez
- R Shroff
- RC Wiegand
- RK Szilard
- S Negrini
- SV Lensing
- V Turinetto
- W Dang
- W Ma
- WH Chung
- WX Yan
- Y Lin
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- Field of study
Identification of G-quadruplex clusters by high-throughput sequencing of whole-genome amplified products with a G-quadruplex ligand
- Author
- A Bedrat
- A Untergasser
- A Verma
- AR Quinlan
- AS Kudlicki
- B Onel
- B Zamiri
- C Timmer
- CC Hardin
- D Rhodes
- D Sen
- DH Bay
- H Li
- J Abraham Punnoose
- J Eddy
- J Eddy
- J Lin
- JL Huppert
- JT Robinson
- K Cao
- K Guo
- K Iida
- K Iida
- K Paeschke
- K Silander
- KV Diveshkumar
- L Blanco.
- M Sakuma
- M Tera
- MJ Law
- ML Bochman
- MM Ribeiro
- P Catasti
- P Mani
- PB Woiczikowski
- R Rodriguez
- T Koressaar
- TA Brooks
- VS Chambers
- W Yoshida
- WI Sundquist
- WJ Chung
- WJ Kent
- Y Kanoh
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- Field of study
Computational Analysis of G-Quadruplex Forming Sequences across Chromosomes Reveals High Density Patterns Near the Terminal Ends
- Author
- A Bugaut
- A von Hacht
- AJ MacQueen
- AK Todd
- AM Zahler
- AS Kudlicki
- CM Phillips
- CM Phillips
- CM Phillips
- D Gomez
- D Karolchik
- D Sen
- Donald M. Miller
- DR Zerbino
- EA Venczel
- Eric C. Rouchka
- Fenfei Leng
- FJ Anscombe
- H Arthanari
- HM Wong
- J Eddy
- J-D Beaudoin
- J-D Beaudoin
- JF Fisette
- JL Huppert
- JL Huppert
- Julia H. Chariker
- KR Rosenbloom
- L Petraccone
- M Krzywinski
- M Qin
- M Subramanian
- M-C Didiot
- ML Bochman
- MM Ribeiro
- N Maizels
- P Kumar
- P Sirand-Pugnet
- R Edgar
- RS Hawley
- S Cogoi
- S Kumari
- S Ray
- SL Palumbo
- V Brázda
- V Marcel
- V Matys
- VS Chambers
- W Huang
- Y Zhang
- ZT-Y Tsai
- Publication venue
- 'Public Library of Science (PLoS)'
- Publication date
- Field of study
Chemical components
- Author
- A Adoutte-Panvier
- A Agthoven Van
- A Coddington
- A Decken Von Der
- A Genot
- A Genot
- A Hampe
- A Inagaki
- A Inagaki
- A Krystosek
- A Kumar
- A Larsen
- A Lin
- A Lin
- A Lin
- A Lind
- A Metspalu
- A Pestana
- A Pestana
- A Rodgers
- A Savic
- A Trewavas
- A Uschewa
- A-M Ladhoff
- AA Azad
- AA Azad
- AA Azad
- AA Azad
- AA Hadjiolov
- AAJ Lugnier
- AB Bransgrove
- AB Henderson
- AC Peacock
- AD Rankine
- AD Rankine
- AD Rankine
- AG Lambertson
- AG Lambertson
- AG Lambertson
- AG Lambertson
- AG Lambertsson
- AG Saponara
- AG Wildeman
- AGWJ Lausink
- AHGC Rijven
- AJ Agthoven
- AJ Bendich
- AK Abraham
- AL Lu
- AM Gressner
- AM Gressner
- AM Gressner
- AM Gressner
- AM Gressner
- AM Gressner
- AM Gressner
- AM Gressner
- AM Gressner
- AM Hill
- AM Lambowitz
- AM Lambowitz
- AM Maxam
- AM Reboud
- AR Stevens
- AR Subramanian
- AR Subramanian
- AS Spirin
- AW Prestayko
- AW Prestayko
- B Allet
- B Attardi
- B Batts-Young
- B Dujon
- B Henkel
- B Jergil
- B Peeters
- B Peeters
- B Perlis
- B Piechulla
- B Schulz-Harder
- B Schulz-Harder
- B Sollner-Webb
- B Wittmann-Liebold
- BC Sturgill
- BC Sturgill
- BD Korant
- BD Korant
- BEH Maden
- BEH Maden
- BEH Maden
- BEH Maden
- BEH Maden
- BEH Maden
- BEH Maden
- BEH Maden
- BG Barrell
- BG Forget
- BG Forget
- BG Forget
- BG Lane
- BJ Cox
- BL Jones
- BR Jordan
- BR Jordan
- BR Jordan
- BR Jordan
- BR Jordan
- C Barber
- C Bernabeu
- C Bernabeu
- C Blat
- C Bogert Van Den
- C Correze
- C Eil
- C Eil
- C Eil
- C Freienstein
- C Glotz
- C Gualerzi
- C Gualerzi
- C Gualerzi
- C Gualerzi
- C Haegeman
- C Judes
- C Rodrigues-Pousada
- C Smith
- C Vaslet
- C Waldron
- C Wikman
- C Zwieb
- C-C Li
- C-Y Ting Shih
- C-YT Shin
- CC Liew
- CC Liew
- CC Nesset
- CC Sherton
- CC Sherton
- CC Sherton
- CD Ashby
- CE Samuel
- CJ Bostock
- CJ Goldenberg
- CJ Leaver
- CJ Leaver
- CJ Leaver
- CJ Madrzak
- CM Bowman
- CS Rubin
- D Barritault
- D Becker-Ursic
- D Boersma
- D Boersma
- D Cavanagh
- D Grierson
- D Kabat
- D Kabat
- D Kabat
- D Koffler
- D Konecki
- D Lightfoot
- D Monier
- D Munsche
- D Sankoff
- D Sankoff
- D Schiffman
- D Trachewsky
- DA Tepfer
- DE Leister
- DE Leister
- DE Matthews
- DG Comb
- DG Hughes
- DG Hughes
- DJ Kuter
- DJ Kuter
- DK Burns
- DP Leader
- DP Leader
- DP Leader
- DP Leader
- DP Leader
- DP Leader
- DP Leader
- DP Leader
- DP Leader
- DP Leader
- DR Pring
- DR Samols
- DR Tolan
- DT Dubin
- DT Dubin
- DT Dubin
- DZ Staynov
- E Belmonte
- E Berger
- E Collatz
- E Collatz
- E Collatz
- E Coppin-Raynal
- E Darzynkiewicz
- E Godwin
- E Kaltschmidt
- E Kaltschmidt
- E Niles
- E Otaka
- E Otaka
- E Selker
- EH McConkey
- EH McConkey
- EH McConkey
- EM Orozco Jr.
- EMB Rodrigues
- ER Burka
- EW Lamon
- EW Lamon
- F Amaldi
- F Amaldi
- F Creusot
- F Galibert
- F Hernandez
- F Kanda
- F Laceur
- F Noll
- F Noll
- F Noll
- F Sanchez-Madrid
- F Sanchez-Madrid
- F Sor
- F Sor
- F Takaiwa
- F Takaiwa
- F Takaiwa
- FA Ventimiglia
- FAM Alberghina
- FAM Alberghina
- FN Chang
- FN Chang
- G Attardi
- G Belanger
- G Bellemare
- G Blobel
- G Bruening
- G Dessev
- G Faye
- G Faye
- G Freyssinet
- G Freyssinet
- G Freyssinet
- G Galling
- G Hallermayer
- G Kramer
- G Lemieux
- G Lutsch
- G Lutsch
- G Oda
- G Spohr
- G Stöffler
- G Stöffler
- G Stöffler
- G Thomas
- G Thomas
- GA Floyd
- GA Howard
- GA Howard
- GA Howard
- GA Luoma
- GA Luoma
- GA Luoma
- GC Majumder
- GE Blair
- GE Fox
- GG Brownlee
- GG Brownlee
- GJ Acton
- GJ Thomas Jr.
- GJ Thomas Jr.
- GK Haselbacbcer
- GK Haselbacher
- GM Hataway
- GM Rubin
- GM Rubin
- GM Veldman
- GM Walton
- GM Walton
- GN Pavlakis
- GN Stöffler
- GW Tischendorf
- H Alberty
- H Bielka
- H Bielka
- H Bielka
- H Bielka
- H Bielka
- H Bielka
- H Bielka
- H Bielka
- H Bielka
- H Boedtker
- H Busch
- H Böhm
- H Fabian
- H Hori
- H Hori
- H Hori
- H Hori
- H Hori
- H Ishikawa
- H Ishikawa
- H Ishikawa
- H Ishikawa
- H Ishikawa
- H Jäckle
- H Kalthoff
- H Komiya
- H Komiya
- H Komiya
- H Komiya
- H Komiya
- H Küntzel
- H Ochiai
- H Pratt
- H Rothschild
- H Spiess
- H Spiess
- H Theise
- H Theise
- H Thomas
- H Thomas
- H Welfle
- H Welfle
- H Welfle
- H Welfle
- H Welfle
- H Welfle
- H Welfle
- H Yamamura
- H-G Wittmann
- H-K Hochkeppel
- H-P Ramjoue
- HJ Bohnert
- HJ Gould
- HJ Gould
- HJ Gould
- HJ Rahmsdorf
- HJ Rahmsdorf
- HN Lightfoot
- Huynh-Van-Tan
- Huynh-Van-Tan
- HWS King
- HWS King
- I Eperon
- I Grummt
- I Horak
- I Horak
- I Horak
- I Junghahn
- I Rosnitschek
- I Tazawa
- I Winicov
- IC Sundkyist
- IG Wool
- IG Wool
- IG Wool
- IM Kennedy
- IS Edelman
- J Behlke
- J Benhamou
- J Benhamou
- J Bequeret
- J Delaunay
- J Delaunay
- J Delaunay
- J Delaunay
- J Delaunay
- J Delaunay
- J Delaunay
- J Gordon
- J Hebert
- J Hindley
- J Ishiguro
- J Klein
- J Klootwijk
- J Klootwijk
- J Klootwijk
- J Klootwtjk
- J Kruppa
- J Langner
- J Langner
- J Marvaldi
- J Panijel
- J Panijel
- J Retèl
- J Sandermann
- J Shine
- J Shine
- J Shine
- J Stahl
- J Stahl
- J Stulz
- J Sy
- J Wikman-Coffelt
- J Woledge
- J-C Homberg
- J-F Houssais
- J-J Madjar
- J-L Darlix
- J-P Cecchini
- J-P Waller
- JA Hunt
- JA Hunt
- JA Lewis
- JA Traugh
- JA Traugh
- JA Traugh
- JA Traugh
- JA Traugh
- JB Curry
- JB Curry
- JD Watson
- JE Loeb
- JF Dice
- JF Giorgini
- JF Thompson
- JG Meyer-Bertenrath
- JG Meyer-Bertenrath
- JH Sinclair
- JH Strauss Jr.
- JJ Buskirk Van
- JJ Buskirk Van
- JJ Madjar
- JJ Müller
- JJ Pene
- JK Hoober
- JK Vass
- JL Nichols
- JM Kelly
- JM Kelly
- JM Verma
- JMW Slack
- JMW Slack
- JMW Slack
- JN Davidson
- JP Goddard
- JP Morrow
- JP Vandrey
- JR Greenberg
- JR Prey
- JR Rawson
- JW Macinnes
- K Egawa
- K Higashi
- K Higo
- K Igarashi
- K Inaba
- K Kanai
- K Kristiansen
- K Kristiansen
- K Kristiansen
- K Kristiansen
- K Nishikawa
- K Nishikawa
- K Nishikawa
- K Nishikawa
- K Nishikawa
- K Ogata
- K Ohtsuki
- K Sakuma
- K Takai
- K Terao
- K Terao
- K Terao
- K Tsurugi
- K Tsurugi
- K Tsurugi
- KD Tartof
- KG Skryabin
- KL Roy
- KL Roy
- KL Roy
- KM Oakden
- KR Luehrsen
- KXL Sfrague
- L Bitte
- L Dalgarno
- L Gyurjan
- L Kokileva
- L Reijnders
- L Reijnders
- L Simpson
- L Weber
- LA Grivell
- LE Hatlen
- LJ Korn
- LJ Mets
- LJ Mets
- LL Houston
- LMC Hall
- LP Yisentin
- M Arpin
- M Brügger
- M Cannon
- M Cazillis
- M Crotjzet
- M Crouzet
- M Cuny
- M Fehlmann
- M Fehlmann
- M Fuke
- M Fuke
- M Fuke
- M Fuke
- M Fuke
- M Girolamo Di
- M Goerl
- M Kaerlein
- M Kaerlein
- M Kel’ve
- M Klagsbrun
- M Knälmann
- M Longuet
- M Miyazaki
- M Miyazakt
- M Pellegrini
- M Perrot
- M Pierre
- M Reporter
- M Reporter
- M Saleem
- M Salevi
- M Salim
- M Salim
- M Sanecka-Obacz
- M Spencer
- M Wegnez
- M Yamamoto
- M-E Eladari
- M-E Eladari
- M-P Ollier
- M-T Ploumhans
- MA Machatt
- MA Siwecka
- MA Treloar
- MA Treolar
- MA Wild
- MC Liau
- MD Griswold
- ME Eladari
- ME Eladari
- ME Eladari
- ME Soergel
- MG Hamilton
- MG Hamilton
- MG Hamilton
- MH Vaughan
- MI Levyant
- MI Levyant
- MI Levyant
- MJ Averner
- MJ Miller
- ML Birnstiel
- ML Cawthon
- ML Fenwick
- ML Petermann
- MOJ Olson
- MR Hanson
- MR Hartley
- MS Ahmad
- MS Odintsova
- MSN Khan
- MSN Khan
- MSN Khan
- MSN Khan
- MSN Khan
- MSN Khan
- MT Jalkanen
- MW Gray
- MW Gray
- MW Gray
- N Barden
- N Fischer
- N Granboulan
- N Grankowski
- N Grankowski
- N Hanna
- N Hanna
- N Nagabhushan
- N Ohta
- N Scherberg
- N-H Chua
- NA Gumilevskaya
- NH Lubsen
- NJ Bigley
- NR Pace
- NR Pace
- NT Van
- O Hagenbüchle
- O-G Issinger
- O-G Issinger
- O-G Issinger
- O-G Issinger
- OC Ingebretsen
- OHW Martini
- OHW Martini
- OHW Martini
- OHW Martini
- OHW Martini
- OHW Martini
- OW Odom
- P Borst
- P Cammarano
- P Cammarano
- P Cayeux
- P Fellner
- P Heizmann
- P HüVös
- P Hüvös
- P Jeanteur
- P Jonge de
- P Jonge de
- P Noll
- P Noll
- P Noll
- P Sanchez-Madrid
- P Sanger
- P Siekevitz
- P Siekevitz
- P Stambrook
- P Tiollais
- P Valenzuela
- P Westermann
- P Westermann
- P Westermann
- P Westermann
- P Westermann
- P Westermann
- P Wrede
- PA Lava-Sanchez
- PA Scolntk
- PF Spahr
- PG Connors
- PG Dondi
- PH Schur
- PI Payne
- PI Payne
- PI Payne
- PJ Ford
- PJ Ford
- PJ Ford
- PJ Payne
- PK Sarkar
- PK Wellauer
- PK Wellauer
- PK Wellauer
- PL Wejksnora
- PL Wollenzien
- PM Rubtsov
- POP Ts’o
- PR Whitfeld
- PS Leboy
- PW Gray
- PWL Tas
- R Amons
- R Amons
- R Amons
- R Baer
- R Brimacombe
- R Brimacombe
- R Kanamaru
- R Kominami
- R Levis
- R Mache
- R Miassod
- R Reyes
- R Schneeman
- R Spencer
- R Vigne
- R Vigne
- R Williamson
- R Williamson
- RA Bosselman
- RA Bosselman
- RA Bosselman
- RA Bosselman
- RA Collins
- RA Cox
- RA Cox
- RA Cox
- RA Cox
- RA Cox
- RA Cox
- RA Cox
- RA Cox
- RA Cox
- RA Cox
- RA Cox
- RA Etten Van
- RA Garrett
- RA Weinberg
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- RB Koser
- RB Low
- RB Low
- RB Schutgens El
- RC Bos Van Den
- RC Brand
- RC Brand
- REH Wettenhall
- REH Wettinsall
- RG Rupp
- RJ Baer
- RJ Baer
- RJ Cedergren
- RJ Cotter
- RK Busch
- RL Gourse
- RL Gourse
- RL Hallberg
- RM Mackay
- RM Mackay
- RM Mackay
- RM Schwartz
- RN Nazar
- RN Nazar
- RN Nazar
- RN Nazar
- RN Nazar
- RN Nazar
- RN Nazar
- RN Nazar
- RN Nazar
- RN Nazar
- RN Nazar
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- RN Nazar
- RN Nazar
- RN Nazar
- RN Nazar
- RP Perry
- RS Cunningham
- RS Cunningham
- RT Garvin
- RV Miller
- RY Latt
- S Ackerman
- S Awata
- S Azhar
- S Böhm
- S Böhm
- S Crews
- S Daubert
- S Fogel
- S Gowda
- S Hashimoto
- S Hashimoto
- S Higo
- S Kelly
- S Maruyama
- S Maruyama
- S Olsnes
- S Osawa
- S Ramagopal
- S Roberts
- S Roberts
- S Zinker
- S Zinker
- SA Garbi
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- SJS Hardy
- SK Chatterjee
- SM Lastick
- SM Lastick
- SM Lastick
- SS Kerwar
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- SW Applebaum
- T Fujisawa
- T Fujisawa
- T Hultin
- T Hultin
- T Itoh
- T Itoh
- T Itoh
- T Itoh
- T Kruiswijk
- T KruiswijK
- T Kruiswijk
- T Kruiswijk
- T Kruiswtjk
- T Schmidt
- T Yagura
- TA Bickle
- TA Dyer
- TA Walker
- TD Barela
- TE Martin
- TE Martin
- TI Sukhova
- TO Sitz
- TV Grancharova
- U Schibler
- U Schneider
- U Swida
- U Ücer
- UE Loening
- UE Loening
- UK Schubart
- V Mutolo
- VA Erdmann
- VA Erdmann
- VA Erdmann
- VA Erdmann
- VE Reichenberger Jr.
- VH Vernay Du Jr.
- W Czempiel
- W Kudlicki
- W Kudlicki
- W Kudlicki
- W McClements
- W Möller
- W Zillig
- WF Doolittle
- WH Anderson
- WJ Murphy
- WL Hofeman
- WL Hoffman
- WL Hoffman
- WL Hoffman
- WL Hoffman
- WM Stanley Jr.
- WY Chooi
- WY Chooi
- Y Cenatiempo
- Y Kuriyama
- Y Leick
- Y Ohtaka
- Y Tanaka
- YC Choi
- YC Choi
- YC Choi
- YC Choi
- YP Wong
- YS Bylinkina
- Z Schwarz
- É Fekete
- Ö Gaal
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 01/01/1982
- Field of study
Edoxaban versus warfarin in patients with atrial fibrillation
- Author
- Abdullakutty J
- Abi-Mansour P
- Abril SB
- Accini J
- Accini M
- Acikel M
- Acikel M
- Adachi C
- Adams K
- Adams K
- Adamus J
- Adler J
- Adler P
- Agarwal D
- Aggarwal R
- Aggarwal R
- Agirov M
- Agraou B
- Ahmad A
- Ahmadpour H
- Ahuad Guerrero R
- Ajioka M
- Akhter F
- Akihisa U
- Akilli H
- Al-Maliky T
- Al-Zoebi A
- Albert L. Waldo
- Albisu J
- Albulescu P
- Alexander J
- Alexandrova L
- Alexopoulos D
- Alexopoulos D
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- Aliyar P
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- Ŝpinar J
- Publication venue
- 'Massachusetts Medical Society'
- Publication date
- 01/01/2013
- Field of study
Contains fulltext :
125374.pdf (publisher's version ) (Open Access)BACKGROUND: Edoxaban is a direct oral factor Xa inhibitor with proven antithrombotic effects. The long-term efficacy and safety of edoxaban as compared with warfarin in patients with atrial fibrillation is not known. METHODS: We conducted a randomized, double-blind, double-dummy trial comparing two once-daily regimens of edoxaban with warfarin in 21,105 patients with moderate-to-high-risk atrial fibrillation (median follow-up, 2.8 years). The primary efficacy end point was stroke or systemic embolism. Each edoxaban regimen was tested for noninferiority to warfarin during the treatment period. The principal safety end point was major bleeding. RESULTS: The annualized rate of the primary end point during treatment was 1.50% with warfarin (median time in the therapeutic range, 68.4%), as compared with 1.18% with high-dose edoxaban (hazard ratio, 0.79; 97.5% confidence interval [CI], 0.63 to 0.99; P<0.001 for noninferiority) and 1.61% with low-dose edoxaban (hazard ratio, 1.07; 97.5% CI, 0.87 to 1.31; P=0.005 for noninferiority). In the intention-to-treat analysis, there was a trend favoring high-dose edoxaban versus warfarin (hazard ratio, 0.87; 97.5% CI, 0.73 to 1.04; P=0.08) and an unfavorable trend with low-dose edoxaban versus warfarin (hazard ratio, 1.13; 97.5% CI, 0.96 to 1.34; P=0.10). The annualized rate of major bleeding was 3.43% with warfarin versus 2.75% with high-dose edoxaban (hazard ratio, 0.80; 95% CI, 0.71 to 0.91; P<0.001) and 1.61% with low-dose edoxaban (hazard ratio, 0.47; 95% CI, 0.41 to 0.55; P<0.001). The corresponding annualized rates of death from cardiovascular causes were 3.17% versus 2.74% (hazard ratio, 0.86; 95% CI, 0.77 to 0.97; P=0.01), and 2.71% (hazard ratio, 0.85; 95% CI, 0.76 to 0.96; P=0.008), and the corresponding rates of the key secondary end point (a composite of stroke, systemic embolism, or death from cardiovascular causes) were 4.43% versus 3.85% (hazard ratio, 0.87; 95% CI, 0.78 to 0.96; P=0.005), and 4.23% (hazard ratio, 0.95; 95% CI, 0.86 to 1.05; P=0.32). CONCLUSIONS: Both once-daily regimens of edoxaban were noninferior to warfarin with respect to the prevention of stroke or systemic embolism and were associated with significantly lower rates of bleeding and death from cardiovascular causes. (Funded by Daiichi Sankyo Pharma Development; ENGAGE AF-TIMI 48 ClinicalTrials.gov number, NCT00781391.)