9 research outputs found
Role of IL-1β in experimental cystic fibrosis upon P. aeruginosa Infection
- Author
- A Bragonzi
- A Saadane
- AM van Heeckeren
- AM van Heeckeren
- B Lubamba
- B Lubamba
- B Villeret
- Bernhard Ryffel
- Bob J. Scholte
- BP O'Sullivan
- Dieudonnée Togbe
- E Faure
- F Ben Mohamed
- F Huaux
- Flora Reverchon
- FS Sutterwala
- GK Griffin
- GU Meduri
- H Levy
- J Laval
- Jennifer Palomo
- JH van Doorninck
- JT Fisher
- Julie Piotet
- KM Hudock
- L Moreno-Vinasco
- Louis Fauconnier
- M Meyer
- M Paroni
- M Wilke
- Marc Le Bert
- Marieke Robinet
- Marta Stolarczyk
- MB Glaccum
- MC Gaspar
- MC Steward
- Min Wu
- MJ Schultz
- NA Turner
- P Gasse
- PJ French
- PR Durie
- R del Campo
- R Legssyer
- RK Ernst
- Ruvalic Buijs-Offerman
- S Kanangat
- S Stick
- S Tirkos
- SH Cheng
- T Nojiri
- T Secher
- TB Tsay
- TH Schroeder
- Tiffany Marchiol
- Valérie F. J. Quesniaux
- Y Shikama
- Y Zhou
- Publication venue
- 'Public Library of Science (PLoS)'
- Publication date
- 01/01/2014
- Field of study
Cystic fibrosis is associated with increased inflammatory responses to pathogen challenge. Here we revisited the role of IL-1β in lung pathology using the experimental F508del-CFTR murine model on C57BL/6 genetic background (Cftrtm1eur or d/d), on double deficient for d/d and type 1 interleukin-1 receptor (d/d X IL-1R1-/-), and antibody neutralization. At steady state, young adult d/d mice did not show any signs of spontaneous lung inflammation. However, IL-1R1 deficiency conferred partial protection to repeated P. aeruginosa endotoxins/LPS lung instillation in d/d mice, as 50% of d/d mice succumbed to inflammation, whereas all d/d x IL-1R1-/- double mutants survived with lower initial weight loss and less pulmonary collagen and mucus production, suggesting that the absence of IL-1R1 signaling is protective in d/d mice in LPS-induced lung damage. Using P. aeruginosa acute lung infection we found heightened neutrophil recruitment in d/d mice with higher epithelial damage, increased bacterial load in BALF, and augmented IL-1β and TNF-α in parenchyma as compared to WT mice. Thus, F508del-CFTR mice show enhanced IL-1β signaling in response to P. aeruginosa. IL-1β antibody neutralization had no effect on lung homeostasis in either d/d or WT mice, however P. aeruginosa induced lung inflammation and bacterial load were diminished by IL-1β antibody neutralization. In conclusion, enhanced susceptibility to P. aeruginosa in d/d mice correlates with an excessive inflammation and with increased IL-1β production and reduced bacterial clearance. Further, we show that neutralization of IL-1β in d/d mice through the double mutation d/d x IL-1R1-/- and in WT via antibody neutralization attenuates inflammation. This supports the notion that intervention in the IL-1R1/IL-1β pathway may be detrimental in CF patients
Delayed Resolution of Lung Inflammation in Il
- Author
- Publication venue
- 'American Thoracic Society'
- Publication date
- Field of study
Cystic fibrosis transmembrane conductance regulator (CFTR) modulators have differential effects on cystic fibrosis macrophage function
- Author
- A Di
- AA Tarique
- AC Tang
- AS Moghaddam
- AV Misharin
- BT Kopp
- BW Ramsey
- C Shi
- C Sorio
- C Sorio
- CE Wainwright
- CE Wainwright
- CL Shrestha
- E Mahenthiralingam
- EM Bruscia
- EM Bruscia
- Emanuela M. Bruscia
- JA Bartlett
- JR Peters-Hall
- Kaivon Assani
- KB Hisert
- KM Hudock
- L Paemka
- LM Yonker
- LS Schlesinger
- M Leveque
- M Leveque
- N Rieber
- Nicholas W. Keiser
- PB Van de Weert-van Leeuwen
- PX Zhang
- R Barnaby
- S Noel
- SA Riquelme
- TJ Cory
- VS Shah
- VS Shah
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- Field of study
MiR‐155 regulates neutrophil extracellular trap formation and lung injury in abdominal sepsis
- Author
- Al‐Haidari AA
- Aman J
- Angelberger P
- Arumugam TV
- Asaduzzaman M
- Bacon KB
- Bansal S
- Bartel DP
- Basit A
- Blanco FF
- Borzone G
- Brinkmann V
- Carraway MS
- De Silanes IL
- Elton TS
- Fan XC
- Faraoni I
- Fuchs TA
- Han Y
- Hawez A
- Hudock KM
- Jiménez‐Alcázar M
- Kilkenny C
- Lefrançais E
- Levi M
- Li X
- Liang Y
- Luo L
- Ma Y
- Mitsunari K
- Moradi F
- Nagase T
- Parrillo JE
- Remick DG
- Rittirsch D
- Sabbione F
- Saffarzadeh M
- Segal AW
- Tacke F
- Valencia‐Sanchez MA
- Wan MX
- Wang Y
- Zhang G‐J
- Zhang XW
- Publication venue
- 'Wiley'
- Publication date
- Field of study
Role of IL-1β in Experimental Cystic Fibrosis upon P. aeruginosa Infection
- Author
- A Bragonzi
- A Saadane
- AM van Heeckeren
- AM van Heeckeren
- B Lubamba
- B Lubamba
- B Villeret
- Bernhard Ryffel
- Bob J. Scholte
- BP O'Sullivan
- Dieudonnée Togbe
- E Faure
- F Ben Mohamed
- F Huaux
- Flora Reverchon
- FS Sutterwala
- GK Griffin
- GU Meduri
- H Levy
- J Laval
- Jennifer Palomo
- JH van Doorninck
- JT Fisher
- Julie Piotet
- KM Hudock
- L Moreno-Vinasco
- Louis Fauconnier
- M Meyer
- M Paroni
- M Wilke
- Marc Le Bert
- Marieke Robinet
- Marta Stolarczyk
- MB Glaccum
- MC Gaspar
- MC Steward
- Min Wu
- MJ Schultz
- NA Turner
- P Gasse
- PJ French
- PR Durie
- R del Campo
- R Legssyer
- RK Ernst
- Ruvalic Buijs-Offerman
- S Kanangat
- S Stick
- S Tirkos
- SH Cheng
- T Nojiri
- T Secher
- TB Tsay
- TH Schroeder
- Tiffany Marchiol
- Valérie F. J. Quesniaux
- Y Shikama
- Y Zhou
- Publication venue
- 'Public Library of Science (PLoS)'
- Publication date
- Field of study
The Influence of Programmed Cell Death in Myeloid Cells on Host Resilience to Infection with Legionella pneumophila or Streptococcus pyogenes
- Author
- A Chawla
- A Choy
- A Karlström
- A Sica
- AA Khweek
- AC Kirby
- AE Lin
- AM Copenhaver
- AM Jamieson
- AM Timmer
- Amanda M. Jamieson
- AO Amer
- B Chang
- BG Byrne
- C Aikawa
- C Fieber
- C Shi
- CL Case
- CS Faherty
- CV Nogueira
- D Fay
- D Hashimoto
- D Schneberger
- D Viasus
- DM Cerqueira
- DM Mosser
- DS Schneider
- DW Fraser
- E Gwyer Findlay
- EK Wright
- ES Van Amersfoort
- F Geissmann
- FR DeLeo
- H Ashida
- H Puthalakath
- HW Virgin
- I Mishalian
- JA Tsatsaronis
- JE McDade
- JS Ayres
- K Krause
- K Labbé
- K Tateda
- Kellyanne Duncan
- KM Hudock
- Lester Kobzik
- LY Gao
- M Cemma
- M Cemma
- M Dinis
- M Molmeret
- M Perl
- Mary O'Riordan
- Mary S
- MC Maiuri
- MD Tate
- MF Fontana
- MR Elliott
- MSF Pereira
- N Gratz
- N Kayagaki
- Nina Gratz
- NL La Gruta
- Pavel Kovarik
- PF Mercer
- Pia Gamradt
- PJ Gough
- PJ Murray
- PW Smit
- Q Lu
- R Chovatiya
- R Kim
- R Medzhitov
- RS Goldszmid
- RS Hotchkiss
- S Banga
- S Edin
- S Gordon
- S Luo
- S Ramaiah
- S Shin
- Sandra Högler
- SB Thacker
- SJ Riedl
- SL Fink
- SL Fink
- SP Blatt
- T Narasaraju
- Thomas Decker
- V Deretic
- Y Aachoui
- Yun Xu
- Publication venue
- 'Public Library of Science (PLoS)'
- Publication date
- Field of study
Epithelial mesenchymal transition (EMT): a universal process in lung diseases with implications for cystic fibrosis pathophysiology
- Author
- A Elizur
- A Mitra
- A Pardo-Saganta
- A Yasukawa
- AC Parsons
- AG Valdivieso
- AM Gonzalez-Guerrico
- B Hu
- C Xiao
- CH Heldin
- CW Jang
- DL Worthley
- DM Minor
- DN Sheppard
- DY Rhyu
- E Roscioli
- EL Rawlins
- F Lutful Kabir
- G Greenburg
- G Zhou
- GC Blobe
- GW Lawson
- H Chen
- H Fujimoto
- H Katagiri
- H Sun
- HR Jonsdottir
- J Baulida
- J Gribbin
- J Li
- J Milara
- J Milara
- J Yang
- J Zavadil
- JA Voynow
- JE Rasmussen
- JK Watson
- JM Collaco
- JM Summy
- JP Maloney
- JR Johnson
- JT Zhang
- K Hosaka
- KK Kim
- KM Hudock
- L Chen
- L Fang
- L Liu
- L Zhang
- L Zhu
- LA Borthwick
- LA Bremer
- LF Loffredo
- LR Stolzenburg
- M Korpal
- M Selman
- M Zeisberg
- ML Drumm
- MM Massip Copiz
- MM Massip-Copiz
- MQ Mahmood
- MQ Mahmood
- NV Jordan
- O Ojo
- P Bonniaud
- P Maisonneuve
- P Spagnolo
- PA Sloane
- PM Quinton
- R Kalluri
- R Shaykhiev
- R Shaykhiev
- R Tarran
- RC Boucher
- RY Wu
- S Agarwal
- S Gronthos
- S Lamouille
- S Nyabam
- S Saito
- SK Halder
- SM Kim
- SM Snodgrass
- SQ Liang
- SS Sohal
- SS Sohal
- ST Gohy
- SV Raju
- SY Moon
- T Grosse-Steffen
- T Wang
- TL Hackett
- VL Battula
- W Zhang
- WH Teo
- X Lan
- X Liu
- X Yang
- XL Zhou
- Y Hou
- Y Kurita
- Y Li
- Y Shirogane
- Y Wang
- YL Zhao
- Z Xiang
- ZC Yang
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- Field of study
Photochemistry of Nucleic Acid Bases and Their Thio- and Aza-Analogues in Solution
- Author
- A Favre
- A Favre
- A Holý
- A Massey
- A Massey
- A Reuther
- A Reuther
- A Sharonov
- AA Lamola
- AF El-Yazbi
- AL Sobolewski
- AM Ababneh
- B Cohen
- B Cohen
- B Kohler
- B Wardle
- BA West
- BA West
- BA West
- BA West
- BE Billinghurst
- BE Billinghurst
- BJ Broughton
- BP Ruzsicska
- C Canuel
- C Middleton
- C Reichardt
- C Reichardt
- C Reichardt
- C Reichardt
- C Salet
- C Salet
- C Salet
- C Santhosh
- C Schweitzer
- C Yang
- C Yang
- C-H Tseng
- CC-W Cheng
- CE Crespo-Hernández
- CE Crespo-Hernández
- CE Crespo-Hernández
- CE Crespo-Hernández
- CL Thomsen
- CM Marian
- CM Perrett
- CT Middleton
- D Asturiol
- D Asturiol
- D Jiang
- D Onidas
- D Voet
- DA McGovern
- DL Kozlowski
- DN Nikogosyan
- EHG Backus
- EN Spremulli
- F Buchner
- F Laermer
- F Santoro
- F Santoro
- F Seela
- F-A Miannay
- FP Gasparro
- G Cui
- G Mędza
- G Wenska
- G Wenska
- G Wenska
- G Wenska
- GJ Fisher
- GJ Fisher
- GM Roberts
- GT Wondrak
- H Görner
- H Görner
- H Kuramochi
- H Saigusa
- HG Zachau
- HR Hudock
- HR Hudock
- I Chorny
- I Conti
- I Penn
- IH Brown
- J Cadet
- J Chen
- J Kára
- J Miyazaki
- J Peon
- J Skoda
- J Wierzchowski
- J Wierzchowski
- J Wierzchowski
- J Wierzchowski
- J-ML Pecourt
- J-ML Pecourt
- JA Montgomery
- JA Poulsen
- JB Nielsen
- JB Nielsen
- JC Bolinger
- JJ Cavaleri
- JJ Szymczak
- JM Ploeser
- JN Freskos
- JN Murrell
- JP Gobbo
- JP Gobbo
- JP Gobbo
- JR Platt
- K Heihoff
- K Kleinermanns
- K Komeda
- K Kosma
- K Raska
- K Taras-Goślińska
- K Taras-Goślińska
- K Taras-Goślińska
- KL Wells
- KM Meisenheimer
- L Blancafort
- L Martinez-Fernandez
- L Martínez-Fernández
- L Serrano-Andrés
- L Serrano-Andrés
- M Barbatti
- M Daniels
- M Daniels
- M Etinski
- M Etinski
- M Lim
- M Merchán
- M Merchán
- M Pollum
- M Richter
- M Shiga
- M Towrie
- M-T Chenon
- M-T Chenon
- MA El-Sayed
- MA El-Sayed
- MC Cuquerella
- MC Stuhldreier
- MG Pleiss
- MJ Peak
- MK Kuimova
- MK Shukla
- MK Shukla
- MM Alam
- MN Lipsett
- MS Chen
- MS Cooke
- MS Vries de
- MZ Zgierski
- N Huse
- N Igarashi-Yamamoto
- NJ Turro
- NR Attard
- NR El-Brollosy
- O Reelfs
- P Drašar
- P Hamm
- P Karran
- P Karran
- P Klán
- P O'Donovan
- P Vigny
- PA Swenson
- PC Mishra
- PF Swann
- PM Hare
- PM Hare
- PM Hare
- PM Keane
- PR Callis
- PR Callis
- Q Zheng
- R Arce
- R Brem
- R Haywood
- R Improta
- R Roblin
- R Schindler
- R Weinshilboum
- RA Vogt
- RE Handschumacher
- RJ Malone
- RV Bensasson
- S Aloïse
- S Mai
- S Marguet
- S Matsika
- S Matsika
- S Matsika
- S Mouret
- S Quinn
- S Yamazaki
- S Yasari
- SE Kaba
- SJ Milder
- SM Bishop
- SS Ng
- SW Prodgeon
- T Climent
- T Climent
- T Elsaesser
- T Gustavsson
- T Gustavsson
- T Gustavsson
- T Gustavsson
- T Gustavsson
- T Gustavsson
- T Gustavsson
- T Kobayashi
- T Kobayashi
- T Kobayashi
- T Kobayashi
- T Pancur
- T Takaya
- V Botan
- V Gomzi
- V Karunakaran
- V Vendrell-Criado
- VJ Hemmens
- W Domcke
- W-M Kwok
- W-M Kwok
- WW Hauswirth
- X Ren
- X Zhang
- X-M Zhu
- Y Harada
- Y Harada
- Y Nosenko
- Y Sanghvi
- Y Zhang
- Y Zhang
- Y Zhang
- Y Zhang
- Z Lan
- Z Lan
- Z Wang
- Ł Szyc
- 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
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- Bohorquez R
- Bohula Erin A.
- Boliek W
- Bolli R
- Bolsman C
- Bonatti S
- Bondi L
- Bondio M
- Bone C
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- Boos C
- Botero R
- Bottzauw J
- Botwin S
- Boudriot E
- Bouvier JM
- Bowden W
- Bozek B
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- Brady A
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- Branzi A
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- Braunwald Eugene
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- Brike C
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- Britto F
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- Brossoit R
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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
- Burley T
- Burton J
- Buss I
- Bustamante G
- Butcher R
- Butkus E
- Butter C
- Buzetti C
- Byfuglien A
- Cabrera-Santamaria A
- Calderón MJ
- Calic S
- Califf
- Calpar I
- Calzolari D
- Campbell C
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- Campos C
- Cannon C
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- Cannon Christopher P.
- Canto J
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- Capucci A
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- Carell E
- Carey C
- Carlessi C
- Carlevaro O
- Carling-Chambers L
- Carlsson F
- Carmelo M
- Carr K
- Carrageta M
- Carrageta M
- Carrageta M
- Carrié D
- Carswell BS
- Cartasegna L
- Caruso O
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- Cassadonte F
- Cassavar D
- Cassel G
- Castoldi M
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- Catarino C
- Caussin C
- Cauthren T
- Cavallini C
- Ceder-Brolin K
- Centeno E
- Centurion C
- Cepeda M
- Cequier A
- Chadwyn D
- Chae SC
- Chalavarya G
- Chambers J
- Chandler G
- Chandna H
- Chandna H
- Chandna H
- Chandra P
- Chandraratna P
- Chandrasekaran S
- Chang D
- Chang G
- Chang K
- Chang K
- Chang M
- Charng M
- Chattree K
- Chavarri M
- Chavez V
- Chee K
- Chernick R
- Chessa P
- Cheung S
- Chew D
- Chhabra A
- Chian-Yi W
- Chiariello M
- Chilakamarri V
- Childs A
- Childs C
- Chiodi L
- Chiu A
- Cho M
- Choi Y
- Cholewa M
- Chopra A
- Chopra V
- Christopher J
- Christy L
- Chronos N
- Chu A
- Chui K
- Chung W
- Ciampricotti R
- Cianflone D
- Cicia G
- Cihalik C
- Ciliberti D
- Cirillo W
- Ciuti G
- Cizinsky S
- Clarke A
- Clarus S
- Clausen H
- Clausen H
- Clavero X
- Clemmensen P
- Cleveland D
- Cleveland T
- Cloud B
- Cobos M
- Cocco N
- Coelho O
- Coetzee C
- Coffin N
- Coffman A
- Cohen B
- Cohen LE
- Cohen Y
- Coisne D
- Coldwell J
- Colfer H
- Collins J
- Collins J
- Collins T
- Colombo H
- Commerford P
- Conaway D
- Connolly T
- Constance C
- Conti M
- Cooke J
- Cooke L
- Corbalan R
- Corbalan R
- Corbett C
- Cortada J
- Corut S
- Cossett J
- Costa M
- Costantini C
- Costello T
- Cottin Y
- Coviaux F
- Coy K
- Craig M
- Crandall L
- Crawford K
- Cristaldi J
- Cristell N
- Cronje T
- Cross D
- Crutchfield B
- Cryderman C
- Csapó K
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- Ångman K
- 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