10 research outputs found
TRAIP is a master regulator of DNA interstrand crosslink repair
- Author
- Publication venue
- Nature Publishing Group
- Publication date
- 06/03/2019
- Field of study
Cells often use multiple pathways to repair the same DNA lesion, and the choice of pathway has substantial implications for the fidelity of genome maintenance. DNA interstrand crosslinks covalently link the two strands of DNA, and thereby block replication and transcription; the cytotoxicity of these crosslinks is exploited for chemotherapy. In Xenopus egg extracts, the collision of replication forks with interstrand crosslinks initiates two distinct repair pathways. NEIL3 glycosylase can cleave the crosslink; however, if this fails, Fanconi anaemia proteins incise the phosphodiester backbone that surrounds the interstrand crosslink, generating a double-strand-break intermediate that is repaired by homologous recombination. It is not known how the simpler NEIL3 pathway is prioritized over the Fanconi anaemia pathway, which can cause genomic rearrangements. Here we show that the E3 ubiquitin ligase TRAIP is required for both pathways. When two replisomes converge at an interstrand crosslink, TRAIP ubiquitylates the replicative DNA helicase CMG (the complex of CDC45, MCM2–7 and GINS). Short ubiquitin chains recruit NEIL3 through direct binding, whereas longer chains are required for the unloading of CMG by the p97 ATPase, which enables the Fanconi anaemia pathway. Thus, TRAIP controls the choice between the two known pathways of replication-coupled interstrand-crosslink repair. These results, together with our other recent findings establish TRAIP as a master regulator of CMG unloading and the response of the replisome to obstacles
TRAIP is a master regulator of DNA interstrand crosslink repair
- Author
- Publication venue
- Nature Publishing Group
- Publication date
- 06/03/2019
- Field of study
Cells often use multiple pathways to repair the same DNA lesion, and the choice of pathway has substantial implications for the fidelity of genome maintenance. DNA interstrand crosslinks covalently link the two strands of DNA, and thereby block replication and transcription; the cytotoxicity of these crosslinks is exploited for chemotherapy. In Xenopus egg extracts, the collision of replication forks with interstrand crosslinks initiates two distinct repair pathways. NEIL3 glycosylase can cleave the crosslink; however, if this fails, Fanconi anaemia proteins incise the phosphodiester backbone that surrounds the interstrand crosslink, generating a double-strand-break intermediate that is repaired by homologous recombination. It is not known how the simpler NEIL3 pathway is prioritized over the Fanconi anaemia pathway, which can cause genomic rearrangements. Here we show that the E3 ubiquitin ligase TRAIP is required for both pathways. When two replisomes converge at an interstrand crosslink, TRAIP ubiquitylates the replicative DNA helicase CMG (the complex of CDC45, MCM2–7 and GINS). Short ubiquitin chains recruit NEIL3 through direct binding, whereas longer chains are required for the unloading of CMG by the p97 ATPase, which enables the Fanconi anaemia pathway. Thus, TRAIP controls the choice between the two known pathways of replication-coupled interstrand-crosslink repair. These results, together with our other recent findings establish TRAIP as a master regulator of CMG unloading and the response of the replisome to obstacles
Use of anticoagulants and antiplatelet agents in stable outpatients with coronary artery disease and atrial fibrillation. International CLARIFY registry
- Author
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- Publication venue
- 'Public Library of Science (PLoS)'
- Publication date
- 01/01/2015
- Field of study
European Society of Cardiology: Cardiovascular Disease Statistics 2019
- Author
- Abdelhamid Magdy
- Abid Leila
- Abir-khalil Saadia
- Achenbach Stephan
- Addad Faouzi
- Ahmeti Artan
- Aladashvili A
- Aliyev Farid
- Anguita Manuel
- Artan Goda
- Aurel Demiraj
- Bajare Iveta
- Bajraktari Gani
- Banu Cristiana
- Baptista Sérgio
- Bardinet Isabel
- Bax Jeroen
- Becker Dávid
- Beissel Jean
- Beleslin Branko
- Beltrame John F
- Bergovec Mijo
- Berisha Gezim
- Berkinbayev Salim
- Bestehorn K
- Boateng Dennis
- Boskovic Aneta
- Bozkurt Engin
- Buttigieg Sandra C
- Carballo David
- Casadei Barbara
- Cequier Ángel
- Chettibi Mohammed
- Chioncel Ovidiu
- Christodoulides Theodoros
- Christou Christos
- Claeys Marc
- Crowley James
- Csanádi Zoltán
- Dalton Barbra
- Daval Ghislain
- De Benito Rubio Víctor
- De Courtelary Paola Thellung
- De Smedt Delphine
- Dikic Ana Djordjevic
- Dizdarević Hudić Larisa
- El Ghamari Fathi
- Ellafi Khaled
- Elsendoorn M W
- Erglis Andrejs
- Erkin Mirrakhimov
- Erol Mustafa Kemal
- Felice Tiziana
- Flather Marcus
- Foscoli Marina
- Fras Zlatko
- Gabrielli Domenico
- Gale Chris P
- Gamkrelidze A
- Gatzov Plamen Marinov
- Gil Victor Machado
- Gilard Martine
- Goudevenos John
- Hammoudi Naima
- Hansen Henrik Steen
- Hatala Robert
- Hindricks Gerhard
- Hlivák Peter
- Holmvang Lene
- Huculeci Radu
- Imantayeva Gulnara
- Indolfi Ciro
- Jahangirov Tofig
- James Stefan
- Jankowski Piotr
- Jegere Sanda
- Johansson Bengt
- Jóna Hrafnkelsdóttir Þórdís
- Kabbani Samer
- Kaliská Gabriela
- Kampus Priit
- Katus H
- Kayıkçıoğlu Meral
- Kazakiewicz Dzianis
- Kearney Peter
- Kenda Miran
- Kereselidze Maia
- Kostov Jorgo
- Kovalenko Volodymyr
- Kristensen Steen Dalby
- Kurbanov Ravshanbek
- Kušljugić Zumreta
- Lancellotti Patrizio
- Le Heuzey Jean-yves
- Lettino Maddalena
- Linhart Ales
- Ludman Peter
- Maggioni Aldo P
- Manak Nikolay
- Marjan Bosevski
- May Heidi T
- Metzler Bernhard
- Milicic Davor
- Mimoso Jorge
- Mimoza Lezha
- Mjølstad Ole Christian
- Mohammed Malek
- Mossialos Elias A
- Moustra Hera Heracleous
- Mrochak Aliaksandr
- Mulder B J M
- Muñiz Javier
- Nesukay Elena
- Niemelä Matti
- Oganov Raphael
- Pasquet Agnès
- Pedrazzini Giovanni B
- Pepoyan Sergey
- Petersen Steffen E
- Platonov Pyotr
- Ponikowski Piotr
- Popescu Bogdan A
- Popovici Mihail
- Rabrenovic Miroslav
- Radovanovic Mina Radosavljevic
- Ray Simon
- Rissanen Tuomas T
- Rustamova Yasmin
- Ryödi Essi
- Saadeh Georges
- Saamay Abilova
- Sakalyte Gintare
- Sarkis Antoine
- Sebastiao David
- Shebli Hussam Eddin
- Shlyakhto Evgeny
- Shokry Khaled
- Siostrzonek Peter
- Sisakian Hamayak
- Slapikas Rimvydas
- Smajić Elnur
- Srbinovska-kostovska Elizabeta
- Steigen Terje
- Taborsky Milos
- Tavazzi Luigi
- Timmis Adam
- Tokmakova Mariya Petkova
- Torbica Aleksandra
- Townsend Nick
- Tsioufis Costas
- Tóth Kálmán
- Urbinati Stefano
- Van Rossum A C
- Vardas Panos
- Viigimaa Margus
- Vinereanu Dragos
- Weidinger Franz
- Witkowski Adam
- Wolak Arik
- Wragg Andrew
- Wright Lucy
- Xuereb Robert G
- Zahger Doron
- Zavatta Marco
- Zeiher A
- Zellweger Michael Johannes
- Ztot Samir
- Zuhlke Liesl
- Zvirblyte Ruta
- Publication venue
- 'Oxford University Press (OUP)'
- Publication date
- 01/01/2019
- Field of study
Aims The 2019 report from the European Society of Cardiology (ESC) Atlas provides a contemporary analysis of cardiovascular disease (CVD) statistics across 56 member countries, with particular emphasis on international inequalities in disease burden and healthcare delivery together with estimates of progress towards meeting 2025 World Health Organization (WHO) non-communicable disease targets. Methods and results In this report, contemporary CVD statistics are presented for member countries of the ESC. The statistics are drawn from the ESC Atlas which is a repository of CVD data from a variety of sources including the WHO, the Institute for Health Metrics and Evaluation, and the World Bank. The Atlas also includes novel ESC sponsored data on human and capital infrastructure and cardiovascular healthcare delivery obtained by annual survey of the national societies of ESC member countries. Across ESC member countries, the prevalence of obesity (body mass index ≥30 kg/m2) and diabetes has increased two- to three-fold during the last 30 years making the WHO 2025 target to halt rises in these risk factors unlikely to be achieved. More encouraging have been variable declines in hypertension, smoking, and alcohol consumption but on current trends only the reduction in smoking from 28% to 21% during the last 20 years appears sufficient for the WHO target to be achieved. The median age-standardized prevalence of major risk factors was higher in middle-income compared with high-income ESC member countries for hypertension {23.8% [interquartile range (IQR) 22.5–23.1%] vs. 15.7% (IQR 14.5–21.1%)}, diabetes [7.7% (IQR 7.1–10.1%) vs. 5.6% (IQR 4.8–7.0%)], and among males smoking [43.8% (IQR 37.4–48.0%) vs. 26.0% (IQR 20.9–31.7%)] although among females smoking was less common in middle-income countries [8.7% (IQR 3.0–10.8) vs. 16.7% (IQR 13.9–19.7%)]. There were associated inequalities in disease burden with disability-adjusted life years per 100 000 people due to CVD over three times as high in middle-income [7160 (IQR 5655–8115)] compared with high-income [2235 (IQR 1896–3602)] countries. Cardiovascular disease mortality was also higher in middle-income countries where it accounted for a greater proportion of potential years of life lost compared with high-income countries in both females (43% vs. 28%) and males (39% vs. 28%). Despite the inequalities in disease burden across ESC member countries, survey data from the National Cardiac Societies of the ESC showed that middle-income member countries remain severely under-resourced compared with high-income countries in terms of cardiological person-power and technological infrastructure. Under-resourcing in middle-income countries is associated with a severe procedural deficit compared with high-income countries in terms of coronary intervention, device implantation and cardiac surgical procedures. Conclusion A seemingly inexorable rise in the prevalence of obesity and diabetes currently provides the greatest challenge to achieving further reductions in CVD burden across ESC member countries. Additional challenges are provided by inequalities in disease burden that now require intensification of policy initiatives in order to reduce population risk and prioritize cardiovascular healthcare delivery, particularly in the middle-income countries of the ESC where need is greatest
Malware Counter-Proliferation and the Wassenaar Arrangement
- Author
- Ben Popper
- Brian Fung
- Chris Grier
- Colin Anderson
- Colin Anderson
- Cora Currier
- Damballa
- Dan Goodin
- Dennis Fisher
- Elizabeth Clarke
- Federico Biancuzzi
- Guillaume Bonfante
- Henry Farrell
- Jen Ellis
- Jennifer Granick
- Julia Wolf
- Karim K Shehadeh
- Kenneth A Dursht
- Kurt Thomas Huang
- Lillian Ablon
- Lucian Constantin
- Mailyn Fidler
- Marquis-Boire
- Marti Motoyama
- Michael Lipson
- Michael Mimoso
- Michael Yip
- Mikko Hypponen
- Nick Ellsmore
- Pamela Samuelson
- S Shepherd
- Sariel Moshe
- Sergey Bratus
- Stan Adams
- Stefan Frei
- T J Holt
- Team Cymru
- Thomas Dullien
- Thomas Dullien
- Tim Maurer
- Trey Herr
- Trey Herr
- Trey Herr
- Trey Herr
- Wassenaar Arrangement
- Publication venue
- 'Elsevier BV'
- Publication date
- 01/01/2016
- Field of study
IL-17 Induces Inflammation-Associated Gene Products in Blood Monocytes, and Treatment with Ixekizumab Reduces Their Expression in Psoriasis Patient Blood
- Author
- Abuabara
- Ahlehoff
- Back
- Boring
- Claire Q.F. Wang
- Claudia A. Mimoso
- David Shrom
- Davidovici
- Di Gregoli
- Ding
- Dixon
- Ernst R. Dow
- Holm
- Jacobsson
- James G. Krueger
- Kerekes
- Kristine E. Nograles
- Krueger
- Madhur
- Mastroianni
- Mayte Suárez-Fariñas
- Mehta
- Michael P. Heffernan
- Mizutani
- Moura
- Okubo
- Papp
- Pietrzak
- Robert W. Hoffman
- Rousselle
- Shahrara
- Smith
- Strober
- Suárez-Fariñas
- Tzellos
- Wen
- Woollard
- Yost
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- Field of study
2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation
- Author
- Abir-Khalil Saadia
- Aboyans Victor
- Achenbach Stephan
- Agewall Stefan
- Aladashvili Alexander
- Andreotti Felicita
- Atalar Enver
- Averkov Oleg
- Badimon Lina
- Bang Lia
- Barrabés José A.
- Barón-Esquivias Gonzalo
- Baumgartner Helmut
- Bax Jeroen J.
- Bax Jeroen J.
- Becker Dávid
- Beishenkulov Medet
- Bolognese Leonardo
- Borger Michael A.
- Brotons Carlos
- Budaj Andrzej
- Bueno Héctor
- Carerj Scipione
- Carneiro Antonio Vaz
- Chew Derek P.
- Chilingaryan Aram
- Collet Jean Philippe
- Dean Veronica
- Eftychiou Christos
- El Etriby Adel
- Erol Çetin
- Fitzsimons Donna
- Gaemperli Oliver
- Gencer Baris
- Ginghina Carmen
- Grosu Aurel
- Guðnason Thorarinn
- Hasenfuss Gerd
- Held Claes
- Kedev Sasko
- Kirchhof Paulus
- Kjeldsen Keld
- Kolh Philippe
- Koning René
- Lancellotti Patrizio
- Lancellotti Patrizio
- Landmesser Ulf
- Larsen Alf Inge
- Latkovskis Gustavs
- Lip Gregory Y H
- Magri Caroline Jane
- Marandi Toomas
- Matetzky Shlomi
- Mehilli Julinda
- Miličić Davor
- Mimoso Jorge M Vieira
- Mourali Mohamed Sami
- Mueller Christian
- Mukherjee Debabrata
- Mussagaliyeva Aisulu
- Najafov Ruslan
- Nedeljkovic Milan A.
- Neumann Franz Josef
- Nihoyannopoulos Petros
- Parkhomenko Alexander
- Patrono Carlo
- Pereira Bruno
- Peters Ron J G
- Piepoli Massimo F.
- Pietilä Mikko
- Ponikowski Piotr
- Postadzhiyan Arman
- Rickli Hans
- Roffi Marco
- Roffi Marco
- Serpytis Pranas
- Sinnaeve Peter R.
- Storey Robert F.
- Studenčan Martin
- Swanson Neil
- Terzić Ibrahim
- Torbicki Adam
- Tsioufis Kostantinos
- Valgimigli Marco
- Weidinger Franz
- Widimsky Petr
- Windecker Stephan
- Windecker Stephan
- Zamorano Jose Luis
- Publication venue
- 'Silicea - Poligraf, LLC'
- Publication date
- 01/03/2016
- Field of study
2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation
- Author
- Abir-Khalil Saadia
- Aboyans Victor
- Achenbach Stephan
- Agewall Stefan
- Aladashvili Alexander
- Andreotti Felicita
- Atalar Enver
- Averkov Oleg
- Badimon Lina
- Baigent Colin
- Bang Lia
- Bar\uf3n-Esquivias Gonzalo
- Barrab\ue9s Jos\ue9 A.
- Baumgartner Helmut
- Bax Jeroen J.
- Bax Jeroen J.
- Becker D\ue1vid
- Beishenkulov Medet
- Bolognese Leonardo
- Borger Michael A.
- Brotons Carlos
- Budaj Andrzej
- Bueno H\ue9ctor
- Bugiardini Raffaele
- Carerj Scipione
- Carneiro Antonio Vaz
- Casselman Filip
- Chew Derek P.
- Chilingaryan Aram
- Collet Jean-Philippe
- Cuisset Thomas
- Dean Veronica
- Eftychiou Christos
- El Etriby Adel
- Erol \uc7etin
- Fitzsimons Donna
- Gaemperli Oliver
- Gencer Baris
- Ginghina Carmen
- Grosu Aurel
- Gu\uf0nason Thorarinn
- Halle Martin
- Hasenfuss Gerd
- Held Claes
- Kedev Sasko
- Kirchhof Paulus
- Kjeldsen Keld
- Kolh Philippe
- Koning Ren\ue9
- Lancellotti Patrizio
- Lancellotti Patrizio
- Landmesser Ulf
- Larsen Alf Inge
- Latkovskis Gustavs
- Lip Gregory Y. H.
- Magri Caroline Jane
- Marandi Toomas
- Matetzky Shlomi
- Mehilli Julinda
- Mili\u10di\u107 Davor
- Mimoso Jorge M. Vieira
- Mourali Mohamed Sami
- Mueller Christian
- Mukherjee Debabrata
- Mussagaliyeva Aisulu
- Najafov Ruslan
- Nedeljkovic Milan A.
- Neumann Franz-Josef
- Nihoyannopoulos Petros
- Parkhomenko Alexander
- Patrono Carlo
- Pereira Bruno
- Peters Ron J. G.
- Piepoli Massimo F.
- Pietil\ue4 Mikko
- Ponikowski Piotr
- Postadzhiyan Arman
- Rickli Hans
- Roffi Marco
- Roffi Marco
- Serpytis Pranas
- Sinnaeve Peter R.
- Storey Robert F.
- Studen\u10dan Martin
- Swanson Neil
- Terzi\u107 Ibrahim
- Torbicki Adam
- Tsioufis Kostantinos
- Valgimigli Marco
- Weidinger Franz
- Widimsky Petr
- Windecker Stephan
- Windecker Stephan
- Zamorano Jose Luis
- Publication venue
- 'Silicea - Poligraf, LLC'
- Publication date
- 01/01/2016
- Field of study
N/
Spherically-symmetric solutions in general relativity using a tetrad-based approach
- Author
- A Friedmann
- A Friedmann
- A Gullstrand
- A Lasenby
- A Mitra
- AE Romano
- AE Romano
- AE Romano
- AN Lasenby
- Anthony N. Lasenby
- BC Nolan
- C Clarkson
- CC Dyer
- CC Dyer
- CW Misner
- D Alonso
- D Lynden-Bell
- D Winter
- Do Young Kim
- DY Kim
- F Melia
- F Melia
- F Melia
- F Melia
- F Melia
- F Melia
- F Melia
- G Lemaître
- G Lemaître
- GC McVittie
- GC McVittie
- GF Lewis
- GF Lewis
- GFR Ellis
- H Bondi
- HP Robertson
- HP Robertson
- HP Robertson
- J Garcia-Bellido
- J Plebanski
- JJ Wei
- JJ Wei
- JJ Wei
- JJ Wei
- JP Mimoso
- JR Oppenheimer
- K Bolejko
- K Kainulainen
- K Lake
- L Nottale
- M Bilicki
- M Harwit
- M Lavinto
- M Lavinto
- Michael P. Hobson
- MJ Rees
- MN Célérier
- N Brouzakis
- N Brouzakis
- N Kaloper
- P Fleury
- P Fleury
- P Le Painlevé
- P Oirschot van
- PD Lasky
- R Caldwell
- R Kantowski
- R Nandra
- R Nandra
- R Nandra
- RA Sussman
- RA Sussman
- RA Sussman
- RA Sussman
- RA Vanderveld
- RC Tolman
- S Alexander
- S Campo del
- S Nadathur
- SD Brechet
- SJ Szybka
- SN Zhang
- SW Hawking
- T Biswas
- T Clifton
- V Marra
- V Marra
- W Israel
- W Israel
- W Valkenburg
- Y Dabrowski
- ÉÉ Flanagan
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- Field of study
Ezetimibe added to statin therapy after acute coronary syndromes
- Author
- Aagnes I
- Aambakk MB
- Aase O
- Aaser E
- Abdel-Latief A
- Abell T
- Aboufakher R
- Abramson B
- Abrantes J
- Achilli A
- Adams A
- Adams K
- Adamus J
- Addington J
- Adgey A
- Adjei A
- Agarwal J
- Aggarwal A
- Aggarwal K
- Aggarwal R
- Agocha A
- Agraou B
- Aguirre O
- Ahmed A
- Ahmed O
- Ahsan A
- Airaksinen J
- Airoldi F
- Aji J
- Akkad H
- Akubzanova E
- Al-Ani R
- Al-Jumaily J
- Alameda J
- Albirini A
- Albuquerque A
- Albuquerque D
- Alcasena S
- Alexander J
- Alfonso F
- Ali MI
- Alings MA
- Allall O
- Allen J
- Allen RP
- Allred S
- Almeira AS
- Alonso L
- Alsagheer S
- Alshaher M
- Altschuller A
- Alvarez J
- Alvarez J
- Alvarez Y
- Alves A
- Amidon T
- Amos M
- Anaszewicz M
- Andersen M
- Andersen O
- Andersson E
- Andersson G
- Andrade G
- Andrade M
- Andrea B
- Andreou C
- Antonangelo A
- Antorrena I
- Appel K
- Arana C
- Aranda M
- Araujo J
- Arce R
- Ardito RV
- Ardito W
- Arend C
- Arias V
- Armada E
- Armstrong P
- Arnold A
- Arnold M
- Arntsen BI
- Arora P
- Aros F
- Arriagada G
- Arriagada G
- Artaecheverria J
- Arvesen K
- Arvigo L
- Ash Y
- Aske R
- Ata N
- Atar D
- Atar S
- Atassi K
- Atieh M
- Atkinson C
- Atzenhofer-Baumgartner K
- Auer J
- Aug L
- Ausen K
- Aycock G
- Aylward P
- Aylward P
- Ayres T
- Azize G
- Azrin M
- Azzolini P
- Babu R
- Bach R
- Badings EA
- Baeza N
- Baig M
- Baiz A
- Bajcsi É
- Balaguera J
- Balcells E
- Baldari D
- Baldus S
- Bali H
- Ballantyne C
- Ballmer P
- Banerjee S
- Bang-Hansen T
- Banikova A
- Bankowski D
- Banks K
- Bansal M
- Baraona F
- Barber C
- Barber C
- Barbir M
- Barillas O
- Barnes D
- Barnett O
- Barr C
- Barrett J
- Barringhaus K
- Barron M
- Bartels GL
- Basilio E
- Bass M
- Bassand J
- Bassand JP
- Bassand JP
- Basso V
- Bata I
- Battikadi S
- Battin D
- Bauer B
- Baumanns S
- Bautista J
- Bayat J
- Bayer M
- Bayer M
- Bayles A
- Bazzi A
- Beaudry M
- Bedoya R
- Been M
- Belicova M
- Bell K
- Belle L
- Beloscar J
- Beltran R
- Beltrano MC
- Ben-Aharon J
- Ben-Yehuda O
- Benetar J
- Bengtsson PO
- Bennermo M
- Bennett J
- Benyahya L
- Beresford P
- Berezniakov I
- Berger M
- Berger-Kucza A
- Bergeron J
- Berglund M
- Berglund R
- Bergsten J
- Berk M
- Berli M
- Bernardi D
- Berra F
- Berrospi P
- Bertolet B
- Bescos L
- Bethea C
- Bethencourt A
- Betti I
- Betzu R
- Bhalla H
- Bhalodkar N
- Bhargava M
- Bhargava R
- Bhargavi M
- Bhesania T
- Biasucci L
- Biedermann B
- Bikkina M
- Bilazarian S
- Bilodeau N
- Bin Ismail O
- Binaghi G
- Birkemeyer R
- Birnbaum Y
- Bishop A
- Bishop B
- Bishop C
- Bissett J
- Bissett J
- Bittel B
- Bitzer V
- Bjornstad H
- Blacher MG
- Blais D
- Blank E
- Blazing M
- Blazing M
- Blazing M
- Blazing Michael A.
- Blessing E
- Block D
- Bluguermann J
- Blumberg E
- Bobek M
- Bocconcelli P
- Bocconcelli P
- Bodanese L
- Bodenstein W
- Boehm S
- Bogomolny N
- Bohle D
- Bohlscheid V
- Bohorquez R
- Bohula Erin A.
- Boliek W
- Bolli R
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- Bouvier JM
- Bowden W
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- Branzi A
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- Braunwald Eugene
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- Britto F
- Broadwater S
- Bronnum-Schou J
- Brossoit R
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- Brunelli C
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- Brussee H
- Bryniarski L
- Budzon S
- Bueno M
- Buerke M
- Buerke M
- Bugos V
- Buijs EM
- Buijs F
- Bullivant M
- Burgess L
- Burghard S
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- Burton J
- Buss I
- Bustamante G
- Butcher R
- Butkus E
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- Calderón MJ
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- Calpar I
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- Cannon Christopher P.
- Canto J
- Cappelen H
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- Carswell BS
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- Chiariello M
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- Childs A
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- Christopher J
- Christy L
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- da Costa FA
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- De Caterina R
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- De Ferrari Gaetano M.
- De Ferrari GM
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- de Lemos J
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- De Lucca Paul
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- de Souza J
- de Teresa E
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- Delahaye F
- Delgado J
- Delio-Cox B
- Della Siega A
- Dellatorre M
- Dellborg M
- Dellborg M
- Dellborg M
- Delport E
- Demarcq JM
- Dempsey K
- Den Hartog FR
- DeRaad R
- Desai V
- Desalca M
- DeSimone L
- DeVault S
- Devlin G
- Dhooghe G
- Di Biase M
- Di Fazio J
- Di Pasquale G
- Diadema B
- Dias D
- Dickinson D
- Dietz S
- Dietz W
- Diffenback M
- Dignen K
- Dijkshoorn-Giesen AH
- Dimenna J
- Diogo A
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- Doerr M
- Dohmann H
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- Donnelly B
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- Dos Santos LB
- Doty W
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- Doughty A
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- Dourmap-Collas C
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- Drexel H
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- Duarte YC
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- Dunselman PH
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- Elsner G
- Emanuele V
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- Fageraas ER
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- Fahdi I
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- Forgione C
- Forgione M
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- Giugliano Robert P.
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- Goldberg R
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- Gunderson J
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- Gurfinkel E
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- Gurlek C
- Gutierrez C
- Gutierrez M
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- Guzniczak E
- Gyetvai I
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- Wiviott Stephen D.
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- Édes I
- Östberg 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