4 research outputs found
Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease
- Author
- A Abbate
- A Abhyankar
- A Adams
- A Agafina
- A Akyea-Djamson
- A Alan
- A Alfieri
- A Alfrey
- A Alvarisqueta
- A Amos
- A Anadiotis
- A Anneveldt
- A Antolick
- A Arthur
- A Aslam
- Abaci F
- Abdullakutty J
- Abhaichand R
- Abib E Jr
- Aboufakher R
- Abrantes J
- Abreu M
- Abulencia K
- Acampora D
- Acampora M
- Accini Mendoza Jl
- Aceto L
- Acevedo B
- Acevedo L
- Acheatel R
- Actis Mv
- Adams M
- Adjic Nc
- Affaki Gs
- Agarwal Dk
- Aggarwal Rk
- Agosta Gf
- Aguilar M
- Aguilar M
- Ahire N
- Ahmad I
- Ahmed Sh
- Ahn Y
- Aish B
- Aiub F
- Aiub J
- Ajax K
- Ajioka M
- Akai Y
- Akatova E
- Akrap B
- Al Joundi T
- Al-Khalili F
- Albisu J
- Alcalde Jm
- Alcide P
- Alfonso T
- Allen J
- Alllison Dc
- Almaliky T
- Amerena J
- Andersen K
- Andor M
- Angelova I
- Angiolillo D
- Anita S
- Anker Sd
- Antalik L
- Antonicelli R
- Aparicio Cv
- Apel T
- Apostolovic S
- Ara M
- Aragorn L
- Arango Jl
- Araujo Fonseca M
- Ardissino D
- Arenas Leon Jl
- Arevalo S
- Argiolas G
- Arif I
- Armas E
- Aron G
- Arora S
- Asafu-Adjaye N
- Ashcom T
- Ashford M
- Ashino K
- Asim Oktay Ao
- Assarsson E
- Ata B
- Ather N
- Atieh M
- Aull L
- Avalos V
- Avdonina N
- Awasthi Ak
- Axthelm C
- Ayala M
- Ayasse D
- Ayasse M
- Azizad M
- Azize Gm
- B Becker
- Baar M
- Babu R
- Backer T
- Badea C
- Baden M
- Baehl S
- Baek C
- Baeumer A
- Bagi Es
- Bai A
- Bailey K
- Bailey S
- Bair S
- Baker A
- Baker C
- Bakhai A
- Bakker H
- Baksi A
- Baldin Mg
- Bali Hk
- Ballantyne C
- Ballmajo M
- Balode A
- Balukova E
- Bang Sa
- Banker D
- Banker K
- Baquero A
- Barbarash Ol
- Barbato E
- Barbosa E
- Barnett S
- Baron S
- Barreto M
- Barroso A
- Barroso W
- Bartkowiak A
- Bartosh L
- Bartuseviciene S
- Bashir K
- Baszak J
- Bata Ir
- Bayram E
- Beall K
- Beaudry M
- Beauregard La
- Beckett L
- Belejchak P
- Belle Isle J
- Belohlavek J
- Bendelow T
- Bender D
- Benedetti G
- Benjamin S
- Benton J
- Berdoff R
- Berger V
- Bergeron P
- Bergholtz T
- Bergler-Klein J
- Berk M
- Berli Ma
- Bernstein M
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- Berulfsen A
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- Bhadade S
- Bilazarian S
- Bilodeau N
- Binder A
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- Bisne V
- Bitzer V
- Blagdon M
- Blahey M
- Blankenberg S
- Blazsek Z
- Bloch S
- Blom Kb
- Bluemel J
- Blumberg C
- Blumenthal R
- Bocanera M
- Bodanese L
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- Bohra P
- Bohula E
- Boivin Mc
- Bolduc H
- Boley K
- Bolognesi Mg
- Bolsmann C
- Boman K
- Bonner J
- Borrayo Na
- Boström På
- Botelho R
- Botta C
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- Boulanger K
- Bourgeois S
- Bouvy C
- Bowen L
- Boyarkin M
- Bradley A
- Brady L
- Bramlet D
- Brath H
- Braun P
- Bredlau C
- Brickman T
- Briggs S
- Briké C
- Brodmann M
- Brons S
- Brousalis L
- Brouwer M
- Brown C
- Brown N
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- Buchannan C
- Budaj A
- Budassi N
- Budkova J
- Bugan V
- Buhlman S
- Bulashova O
- Bunschoten P
- Burke W
- Burley T
- Burova N
- Burris H
- Burton C
- Burton J
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- Bøen Rh
- C Clavier-Firmin
- C Conradie
- C Contzen
- C Cotes
- C Covert
- C Cuneo
- Caballero-Valiente B
- Cabau Jr
- Calabrese A
- Campanale Eg
- Candusso R
- Cantor W
- CANTOS Trial Group. Krum H
- Capova L
- Carabajal T
- Carr K
- Carrillo J
- Caruso G
- Casala J
- Caso P
- Casoinic F
- Castillo J
- Castillo T
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- Cendali G
- Cepinskiene L
- Cerda L
- Cermak O
- Chachalis G
- Chaggar S
- Chambers J
- Chamblee T
- Chang K
- Chang Kc
- Chang Wh
- Charlier F
- Charmarthi B
- Chattin W
- Chauhan D
- Chauhan H
- Chaussé I
- Chavada J
- Chaverra I
- Chaware G
- Chee L
- Chella S
- Chen Cp
- Chen J
- Chen Mh
- Chen Y
- Chen Yc
- Chen Zc
- Cheng Jj
- Cheng S
- Cheng Sm
- Cherlin R
- Cheung D
- Chhabra A
- Chintala P
- Chiodi L
- Choi Aj
- Chou S
- Chouinard G
- Christensen L
- Christenson S
- Chung A
- Churina S
- Cifkova R
- Ciglenecki N
- Cioffi A
- Cislowski D
- Cleveland T
- Clocotan M
- Cmrecnjak J
- Colfer H
- Colhoun H
- Collier D
- Collins R
- Coloma G
- Colquhoun D
- Colvin T
- Coman S
- Commerford P
- Commerford P
- Conrado Y
- Cools F
- Cornel Jh
- Corona V
- Coronel J
- Cosgrove N
- Cosgrove S
- Cosmi F
- Costa Amorim R
- Coufalova Z
- Covell W
- Cox B
- Cox R
- Craig W
- Crandall L
- Crawford G
- Crea F
- Crepps K
- Crocamo A
- Cromer M
- Cruz H
- Cruz H
- Cruz M
- Csala L
- Cucher F
- Cuentas I
- Cuervo A
- Curiac D
- Cymerman K
- Cyprian R
- Czerski T
- D'Amours Dg
- D Dash
- D Dattani
- D Denham
- D Desai
- D Desalle
- D Digangi
- D Dunn
- Da Costa F
- Da Silva A
- Da Silva D Jr
- Da Silva O Jr
- Dahlen G
- Dalseg Am
- Damron M
- Danik J
- Davalos C
- Dave B
- Dave K
- Davidsson K
- Davies M
- Davies N
- Davis B
- Davis M
- Dawkins-Hughes S
- Dawood Sy
- Dayer M
- De Boer P
- De Caterina R
- De Jong C
- De Knijf K
- De Krumbach L
- De Los Milagros Had M
- De Los Rios M
- De Rosa S
- De Vos A
- De Wolf L
- Dean J
- Debnam S
- Decsi K
- Decsi Kl
- Dedek V
- Dedkova S
- Defosse C
- Degennaro N
- Dehning M
- Dela Llana A
- Delfonso F
- Delforge M
- Delgadillo T
- Dellasa M
- Dellborg M
- Dellorso M
- Demidova M
- Den Hartog F
- Denecke C
- Dengler T
- Dermitzakis A
- Deslongchamps F
- Dessalvi Cc
- Destro M
- Dettmer M
- Devasia T
- Deweerdt N
- Dhanak R
- Dhawan M
- Di Biase M
- Diago M
- Diaz M
- Dicken T
- Dickstein K
- Diederich C
- Diederich M
- Diehl R
- Diller P
- Dimattia M
- Dimitrov G
- Diodati J
- Dobariya H
- Dobilas V
- Dodds G
- Doesborg L
- Doggett J
- Dognini Gp
- Doi M
- Dokupilova A
- Dommerholt R
- Donahue K
- Donath M
- Donaubauer T
- Dong X
- Dormidontova G
- Dorogova I
- Dos Santos A
- Dos Santos F
- Dos Santos P
- Doughty A
- Doughty L
- Dovgalevskiy Y
- Dovgolis S
- Dragutksy B
- Dreese M
- Drost I
- Drouin K
- Duchesne L
- Duckert A
- Duda N
- Dudarev M
- Dudhatra N
- Duff J
- Duhan S
- Dunhurst F
- Dussan Ma
- Dutka C
- Dwenger E
- Dzupina A
- Dékány Jn
- E Eleuteri
- E Englmann
- Earl J
- East C
- Eaton C
- Eaves W
- Ebeling K
- Ebrahim I
- Eccleston D
- Echeverria L
- Eder F
- Edgerton L
- Edillo C
- Edwards J
- Edwards T
- Eichinger G
- Einhorn D
- Eki Y
- El Hachem M
- El Hafi S
- Ellenbroek D
- Ellis M
- Emil B
- Endo T
- Engelen W
- Erhard M
- Erickson B
- Ervin W
- Eskridge L
- Espinosa V
- Everett Bm
- F Fedele
- F Fonseca
- F Fucci
- Facello A
- Facello M
- Faghih M
- Fail P
- Falcon D
- Fang C
- Fang Cy
- Farias E
- Fattal P
- Fawson A
- Feitosa G
- Felario Junior Ga
- Felix L
- Feng Y
- Feng Z
- Ferdinand K
- Ferkl R
- Fernandez Aa
- Ferrari V
- Ferrario M
- Ferraz R
- Ferreira Dos Santos T
- Ferreira-Jardim A
- Fien E
- Filardi Pp
- Filho P
- Fintel D
- Firek C
- Fischer Sm
- Fisher J
- Fitilev S
- Fitz-Patrick D
- Fitzpatrick L
- Flaksa I
- Flather M
- Flezar M
- Fliesser-Goerzer E
- Flores E
- Flores E
- Flores Gs
- Flores H
- Floro T
- Foerster A
- Folkeringa Rj
- Fonseca A
- Fontaine S
- Forgon T
- Forgosh L
- Forker A
- Forster T
- Foster M
- Foucauld J
- Fowler V
- Fox B
- Franco M
- Francoeur L
- Frandsen B
- Frandsen B
- Frankenstein L
- Fratczak M
- Freitas E
- French J
- Frivold G
- Fruchter G
- Fu G
- Fucak E
- Fuchs R
- Fucili A
- Fukuike C
- Fullerton D
- Fulop P
- Fulop T
- Fulwani M
- Furch G
- Furuseth B
- G Gacioch
- G Gosselin
- Gabito A
- Gabor M
- Gabriel J
- Gabrielli D
- Gaeb-Strasas B
- Gamba C
- Ganau A
- Gapon L
- Garas S
- Garcia Duran R
- Garcia Pinna J
- Garcia Rinaldi R
- Garcia F
- Garcia N
- Garcia-Fragoso V
- Garcia-Portela M
- Garner K
- Gazizianova V
- Gelb R
- Genest J
- Genova D
- George F
- Germann H
- Gersh B
- Gervais B
- Ghali J
- Ghondale N
- Ghosh N
- Ghosh S
- Giese C
- Gilbert J
- Gilley J
- Gits F
- Glancy R
- Glenny J
- Glover J
- Glynn Rj
- Godoy Sanchez M
- Goette A
- Goff R
- Goffinet C
- Gohel P
- Goldberg N
- Gomez Sanchez J
- Gonsorcik J
- Gonzales D
- Gonzales V
- Gonzalez E
- Gordeev I
- Gorges R
- Gospodinov K
- Gotcheva N
- Goudev A
- Gould R
- Govindaraj D
- Goyal B
- Goyal S
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- Grable M
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- Graif J
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- Gravellone M
- Gravenhorst-Muenter U
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- Greener R
- Greenway F
- Grieshaber V
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- Grigaraviciene I
- Grigorova V
- Gros C
- Grosse A
- Grover A
- Grundtvig M
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- Guerrero A
- Guillinta P
- Gundala Ak
- Gupta A
- Gupta A
- Gupta M
- Gupta V
- Gutmann J
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- Guzman P
- Gwyn M
- Gyorgyova E
- H Haldane
- H Hansen
- H Haught
- H Hill
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- Haege R
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- Hakas J
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- Han B
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- Hanefeld M
- Hangyal T
- Hansson A
- Hanustiakova A
- Hao Y
- Hardas S
- Hardee L
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- Harrington A
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- Hartleib M
- Hartwell J
- Hasan F
- Hasbani E
- Hasegawa K
- Hattler B
- Haughton G
- Haynes E
- Haywood A
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- Heaney L
- Hecht J
- Heeren G
- Hegedus V
- Heider J
- Heisters J
- Henley L
- Hennig D
- Henriksson A
- Hermans K
- Hernandez E
- Hernandez I
- Hernandez M
- Hernández N
- Herrman Jp
- Herzog W
- Hess E
- Hettwer Magedanz E
- Hickey L
- Hiden C
- Hielscher S
- Higuchi T
- Higuchi Y
- Hilkert R
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- Himpel-Boenninghoff A
- Hinderaker P
- Hioki M
- Hirayama A
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- Hornig M
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- Hsieh Ic
- Huang A
- Huang P
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- Humbert J
- Hurtig U
- Hutchens E
- Huynh T
- Hwang Jj
- Hwang Jj
- Hyun K
- Härstedt N
- Høivik Ho
- I Ilic
- I Ivanov
- Iachini K
- Iannopollo G
- Ibarra J
- Ibarra M
- Ibañez J
- Iby M
- Ichisawa M
- Igbokidi O
- Iijima T
- Ilahi T
- Ilic S
- Ilsley M
- Imbrognio M
- Imre Bs
- Inada T
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- Indolfi C
- Infusino F
- Invitti C
- Ipp E
- Isaza D
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- Iteld B
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- Iveta H
- Izmozherova N
- J Jiang
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- J Johnston
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- Jacques G
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- Jaguszewska G
- Jain A
- Jansen M
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- Jayasinghe R
- Jefferson D
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- Jensen Ed
- Jeric M
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- Jimenez D
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- Johansen Bb
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- Kamensky G
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- Kazanskay E
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- Keenan S
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- M Malek
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- M Mandati
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- Publication venue
- 'Massachusetts Medical Society'
- Publication date
- 01/01/2017
- Field of study
Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.
Synthèses de recherche
- Author
- Publication venue
- 'University of Toronto Medical Journal'
- Publication date
- 01/10/1996
- Field of study
n/
The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2
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- Zuhairy H. M.
- Zukerman L. S.
- Zwaan van der C.
- Publication venue
- 'Elsevier BV'
- Publication date
- 01/01/2017
- Field of study
Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age 6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score 652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701
Antiinflammatory therapy with canakinumab for atherosclerotic disease
- Author
- Abaci F.
- Abbate A.
- Abdullakutty J.
- Abhaichand R.
- Abhyankar A.
- Abib E.Jr.
- Aboufakher R.
- Abrantes J.
- Abreu M.
- Abulencia K.
- Acampora D.
- Acampora M.
- Accini Mendoza JL.
- Aceto L.
- Acevedo B.
- Acevedo L.
- Acheatel R.
- Actis M.V.
- Adams A.
- Adams M.
- Adjic N.C.
- Affaki G.S.
- Agafina A.
- Agarwal D.K.
- Aggarwal R.K.
- Agosta G.F.
- Aguilar M.
- Ahire N.
- Ahmad I.
- Ahmed S.H.
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- Aish B.
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- Ajioka M.
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- Al-Khalili F.
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- Publication venue
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- Publication date
- Field of study
BACKGROUND: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. METHODS: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P=0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P=0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P=0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P=0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P=0.31). CONCLUSIONS: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. Copyright © 2017 Massachusetts Medical Society