5 research outputs found
SARS-CoV-2 infects the human kidney and drives fibrosis in kidney organoids
- Author
- Achdout H.
- Aimon A.
- Akiva A.
- Alexandrov T.
- Bar-David E.
- Barr H.
- Ben-Shmuel A.
- Bennett J.
- Beukenboom M.
- Bindels E.M.J.
- Boby M.L.
- Boor P.
- Borden B.
- Bowman G.R.
- Brun J.
- Bulthuis M.
- BVNBS S.
- Calmiano M.
- Carbery A.
- Cattermole E.
- Chernychenko E.
- Choder J.D.
- Clyde A.
- Coffland J.E.
- Cohen G.
- Cole J.
- Contini A.
- Costa I.G.
- Cox L.
- Cvitkovic M.
- Czogalla J.
- Daviran D.
- de Beer M.
- De Jonghe S.
- Dias A.
- Djudjaj S.
- Donckers K.
- Dotson D.L.
- Douangamath A.
- Duberstein S.
- Dudgeon T.
- Dunnen W.D.
- Dunnett L.
- Eastman P.K.
- Erez N.
- Eyermann C.J.
- Fairhead M.
- Fate G.
- Fearon D.
- Federov O.
- Ferla M.
- Fermin L.A.S.
- Fernandes R.S.
- Ferrins L.
- Floege J.
- Foster H.
- Foster R.
- Gabizon R.
- Garcia-Sastre A.
- Gawriljuk V.O.
- Gehrtz P.
- Gileadi C.
- Giroud C.
- Glass W.G.
- Glen R.
- Godoy A.S.
- Gorichko M.
- Gorrie-Stone T.
- Griffen E.J.
- Grünberg K.
- Hart S.H.
- Heer J.
- Heijnert J.
- Henry M.
- Hill M.
- Hillebrands J.-L.
- Hoogenboezem R.M.
- Horrell S.
- Huber T.B.
- Hurley M.F.D.
- Ijzermans T.
- Israely T.
- Itai glinert
- Jajack A.
- Jansen J.
- Jnoff E.
- Jochmans D.
- John T.
- Kantsadi A.L.
- Kenny P.W.
- Kiappes J.L.
- Koekemoer L.
- Kovar B.
- Kramann R.
- Krojer T.
- Kuppe C.
- Lee A.A.
- Lefker B.A.
- Levy H.
- London N.
- Lukacik P.
- Macdonald H.B.
- Maclean B.
- Malla T.R.
- Mastik M.
- Matviiuk T.
- McCorkindale W.
- McGovern B.L.
- Melamed S.
- Michurin O.
- Miesen P.
- Mikolajek H.
- Milne B.F.
- Mooren F.
- Morris A.
- Morris G.M.
- Morwitzer M.J.
- Moustakas D.
- Nagai J.S.
- Nakamura A.M.
- Neto J.B.
- Neyts J.
- Nguyen L.
- Nlandu Q.
- Noske G.D.
- Oleinikovas V.
- Oliva G.
- Overheul G.J.
- Overheul G.J.
- Owen D.
- Pai R.
- Pan J.
- Paran N.
- Perry B.
- Pingle M.
- Pinjari J.
- Politi B.
- Powell A.
- Psenak V.
- Puelles V.G.
- Puni R.
- Rangel V.L.
- Reddi R.N.
- Reid S.P.
- Reimer K.C.
- Resnick E.
- Ripka E.G.
- Robinson M.C.
- Robinson R.P.
- Rodriguez-Guerra J.
- Rosales R.
- Roverts R.
- Rufa D.
- Schneider R.K.
- Schofield C.
- Schreuder M.F.
- Shafeev M.
- Shaikh A.
- Shi J.
- Shurrush K.
- Sing S.
- Sittner A.
- Skyner R.
- Smalley A.
- Smeets B.
- Smilova M.D.
- Solmesky L.J.
- Sommerdijk N.
- Spencer J.
- Steenbergen E.J.
- Strain-Damarell C.
- Swamy V.
- Tamir H.
- Tennant R.
- Thompson A.
- Thompson W.
- Thompson W.
- Timm M.-C.
- Tomasia S.
- Triana S.H.
- Tumber A.
- Vakonakis I.
- van den Berge B.T.
- van den Broek M.
- van Eijk L.E.
- van Geel L.
- van Goor H.
- van Rij R.P.
- van Rij R.P.
- Varghese F.S.
- Varghese F.S.
- Vaschetto M.
- Vitner E.B.
- Voelz V.
- Volkamer A.
- von Delft A.
- von Delft F.
- von Stillfried S.
- Walsh M.
- Ward W.
- Weatherall C.
- Weiss S.
- White K.M.
- Wild C.F.
- Willemsen B.
- Wittmann M.
- Wright N.
- Yahalom-Ronen Y.
- Zaidmann D.
- Zidane H.
- Zitzmann N.
- Publication venue
- Elsevier
- Publication date
- 03/02/2022
- Field of study
Kidney failure is frequently observed during and after COVID-19, but it remains elusive whether this is a direct effect of the virus. Here, we report that SARS-CoV-2 directly infects kidney cells and is associated with increased tubule-interstitial kidney fibrosis in patient autopsy samples. To study direct effects of the virus on the kidney independent of systemic effects of COVID-19, we infected human-induced pluripotent stem-cell-derived kidney organoids with SARS-CoV-2. Single-cell RNA sequencing indicated injury and dedifferentiation of infected cells with activation of profibrotic signaling pathways. Importantly, SARS-CoV-2 infection also led to increased collagen 1 protein expression in organoids. A SARS-CoV-2 protease inhibitor was able to ameliorate the infection of kidney cells by SARS-CoV-2. Our results suggest that SARS-CoV-2 can directly infect kidney cells and induce cell injury with subsequent fibrosis. These data could explain both acute kidney injury in COVID-19 patients and the development of chronic kidney disease in long COVID
Pervasive gaps in Amazonian ecological research
- Author
- Aguiar D.P.P.D.
- Aguiar H.J.A.C.D.
- Albernaz A.L.
- Albuquerque B.W.
- Aleixo A.
- Alencar L.
- Almeida D.D.F.
- Almeida M.
- Almeida M.R.N.
- Almeida R.P.S.
- Almeida W.R.D.
- Alvarado S.T.
- Alverga P.P.D.P.
- Alves da Rosa C.
- Alves-Martins F.
- Alves-Martins F.
- Amado L.L.
- Amaral D.D.D.
- Anacléto M.J.P.
- Andrade A.L.
- Andrade R.B.D.
- Andrade-Silva J.
- Andresen E.
- Andretti C.B.
- Andriolo A.
- André T.
- Anjos D.V.
- Aragão L.
- Aragão L.
- Arantes C.C.
- Arenas E.R.C.
- Arrolho S.
- Arruda F.V.D.
- Assis R.L.D.
- Azara L.
- Azevêdo C.A.S.D.
- Baccaro F.B.
- Baccaro F.B.
- Baider C.
- Baker T.R.
- Barbosa E.M.
- Barbosa J.F.
- Barbosa R.I.
- Barbosa T.A.P.
- Barlow J.
- Barlow J.
- Barni P.E.
- Barros G.G.
- Barroso J.G.
- Barthem R.
- Bastos D.
- Bastos R.C.
- Batista A.P.B.
- Begot T.O.
- Beiroz W.
- Benetti C.J.
- Benone N.L.
- Bentos T.V.
- Berenguer E.
- Berenguer E.
- Bispo P.C.
- Boldrini R.
- Bonates L.C.D.M.
- Borba G.C.
- Borges A.
- Borges L.H.M.
- Borges S.H.
- Braga D.D.L.
- Braga R.B.
- Brando P.
- Brasil L.S.
- Brejão G.L.
- Brito M.T.D.S.
- Brito T.D.F.
- Brocardo C.R.
- Brown I.F.
- Brulinger L.F.B.
- Bueno A.S.
- Cabeceira F.G.
- Cabette H.S.R.
- Cabral G.S.
- Cajaiba R.L.
- Callisto M.
- Calor A.R.
- Calvão L.B.
- Camargo J.L.
- Camargo P.B.D.
- Campana D.R.D.S.
- Campos N.
- Campos-Filho E.M.
- Cardoso M.R.
- Carim M.D.J.V.
- Carmo G.H.P.D.
- Carniello M.A.
- Carpanedo R.D.S.
- Carreiras J.
- Carvalho F.A.
- Carvalho F.G.
- Carvalho F.R.D.
- Carvalho K.S.
- Carvalho L.C.D.S.
- Carvalho L.N.
- Carvalho R.L.
- Carvalho R.L.
- Casadei-Ferreira A.
- Casatti L.
- Castello L.
- Castello L.
- Castilho C.
- Castro A.B.
- Castro F.S.D.
- Castro W.
- Catarino M.
- Cavalheiro L.
- Cerqueira Silva J.C.
- Cerqueira P.V.
- Cintra B.B.L.
- Cochrane M.A.
- Coelho de Souza F.
- Coelho L.D.S.
- Coletti F.
- Cordeiro C.L.
- Cornelius C.
- Correa A.S.A.S.
- Costa Batista M.
- Costa D.D.S.
- Costa F.R.C.
- Costa F.R.C.
- Costa J.B.P.
- Costa J.G.
- Costa M.K.S.
- Costa M.M.S.D.
- Couceiro S.R.M.
- Cravo J.S.
- Crema L.C.
- Cruz P.V.
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- Cunha E.J.R.D.
- da Rocha M.
- da Silva Guimarães J.R.
- da Silva Menger J.
- da Silva E.R.
- da Silva G.C.
- da Silva J.S.
- da Silva K.D.
- da Silva L.F.
- da Silva M.J.
- da Silva R.R.
- Daly D.
- Damasco G.
- Davis B.
- de Abreu J.C.
- de Albuquerque E.Z.
- de Brito J.G.
- de Faria Falcão J.C.
- de Lima Alves A.
- de Matos L.S.
- de Oliveira Melo L.
- de Resende B.O.
- de Sousa Gorayeb I.
- de Toledo J.J.
- Delabie J.H.C.
- Demarchi L.O.
- Desidério G.R.
- Deus C.P.D.
- Dias M.S.
- do Vale J.D.
- Domingues T.F.
- Doria C.R.D.C.
- dos Anjos M.R.
- Douglas D.
- Duarte Ritter C.
- Dumas L.L.
- Durgante F.
- Dutra D.B.D.S.
- Dutra S.L.
- Dáttilo W.
- d’Horta F.M.
- e Gomes J.O.
- e Pérez R.E.P.
- Edwards D.P.
- Elias F.
- Elias F.
- Emilio T.
- Esposito M.C.
- Espírito Santo N.B.
- Espírito-Santo H.M.V.
- Fadini R.F.
- Fares A.L.
- Faria A.P.J.
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- Feitosa R.M.
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- Feldpausch T.R.
- Fernandes I.
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- Ferreira A.B.
- Ferreira J.
- Ferreira J.
- Ferreira L.V.
- Ferreira N.
- Ferreira-Ferreira J.
- Firmino V.
- Flores B.M.
- Florêncio F.P.
- Fontenele L.
- França F.
- França F.M.
- Freitas C.
- Freitas M.A.B.
- Freitas M.G.
- Félix N.S.
- Galuch A.V.
- Gama Neto J.D.L.
- Gastauer M.
- Geber Filho A.N.D.S.
- Ghidini A.R.
- Giacomin L.
- Giarrizzo T.
- Giehl N.F.D.S.
- Godoy B.S.
- Gomes V.H.F.
- Gontijo A.
- Gonçalves I.C.
- Graça P.M.D.A.
- Griffiths H.
- Gris D.
- Gualberto C.G.
- Guedes M.C.
- Guedes M.L.
- Guedes M.L.
- Guerrero J.E.B.
- Guilherme E.
- Guimaraes A.F.
- Guimarães D.P.
- Görgens E.B.
- Hamada N.
- Haugaasen T.
- Hawes J.E.
- Hercos A.
- Hilário R.R.
- Holanda de Andrade A.L.R.
- Holmgren M.
- Householder E.
- i Silva P.G.D.
- Irume M.V.
- Isaac V.
- Isaac V.
- Ivanauskas N.M.
- Izzo T.J.
- Jakovac C.C.
- Jardim G.A.
- Juen L.
- Juen L.
- Junqueira A.B.
- Korasaki V.
- Koroiva R.
- Krolow T.K.
- Kunz S.H.
- Landeiro V.L.
- Lanna J.
- Laranjeiras T.O.
- Lasky J.R.
- Lasmar C.
- Laurance S.
- Laurance W.
- Leal C.G.
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- Lees A.C.
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- Leitão R.P.
- Levis C.
- Leão H.
- Ligeiro R.
- Lima G.R.
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- Lima Y.G.D.
- Lobato C.M.C.
- Lopes A.
- Lopes M.A.
- Lourenço L.D.S.
- Louzada J.
- Luize B.G.
- Luther D.
- Machado T.L.D.S.
- Maciel R.
- Maciel R.
- Magalhães J.L.L.
- Magnusson W.E.
- Mahood S.
- Maia L.F.
- Maldaner M.E.
- Malhi Y.
- Manzatto A.G.
- Maracahipes L.
- Maracahipes-Santos L.
- Mariano R.
- Marimon B.S.
- Marimon-Junior B.H.
- Marques E.E.
- Marsh C.J.
- Martins M.F.D.O.
- Martins M.P.
- Martins R.T.
- Massam M.R.
- Matavelli R.
- Maximiano M.F.D.A.
- Mazzei L.
- Medeiros H.
- Medeiros M.B.D.
- Medeiros N.
- Melgaço K.
- Melinski R.D.
- Melo Lima D.V.
- Melo A.W.F.D.
- Melo B.S.B.D.
- Melo G.D.C.D.
- Mendes Aguiar J.J.
- Mendes K.R.
- Mendes R.N.G.
- Mendes T.P.
- Mendonça F.P.
- Menezes A.S.O.D.
- Mestre L.A.M.
- Metcalf O.C.
- Michelan T.S.
- Miguel T.B.
- Milheiras S.
- Milliken W.
- Miranda I.P.D.A.
- Miranda P.N.
- Montag L.F.D.A.
- Monteiro Jr. C.D.S.
- Monteiro M.G.T.
- Morandi P.S.
- Morato E.F.
- Moreira F.F.F.
- Mormul R.P.
- Mortati A.F.
- Moser P.
- Moura M.R.
- Moura M.R.
- Muelbert A.E.
- Muñoz Gutiérrez J.A.
- Naka L.N.
- Nascimento H.E.M.
- Nascimento M.T.
- Nascimento R.O.
- Nascimento R.O.
- Navarro Paolucci L.
- Nelson B.
- Nessimian J.L.
- Neto F.V.
- Nichols E.
- Nienow S.
- Nogueira D.S.
- Nonato F.A.D.S.
- Noriega J.A.
- Noronha J.C.
- Novo E.M.M.D.L.
- Nunes C.A.
- Nunes C.A.
- Nunes L.G.D.O.
- o Santos M.P.D.
- Obermuller F.A.
- Oliveira Pes A.M.
- Oliveira A.A.D.
- Oliveira A.B.D.S.D.
- Oliveira C.P.D.
- Oliveira E.A.D.
- Oliveira F.F.D.
- Oliveira J.M.B.
- Oliveira M.A.D.
- Oliveira M.V.N.D.
- Oliveira R.L.C.D.
- Oliveira S.A.V.D.
- Oliveira V.C.D.
- Oliveira V.H.F.
- Oliveira W.L.D.
- Olivo Neto A.M.
- Pansonato M.P.
- Passos M.I.S.
- Paula W.S.D.
- Pauletto D.
- Pedroza D.
- Peixoto U.
- Penagos C.C.M.
- Perdiz R.D.O.
- Pereira J.L.D.S.
- Peres C.A.
- Peruquetti P.S.F.
- Phillips O.L.
- Phillips O.L.
- Piedade A.R.D.
- Piedade M.T.F.
- Pombo M.M.
- Pompeu P.D.S.
- Pontes-Lopes A.
- Pozzobom U.M.
- Prado L.P.D.
- Prance G.T.
- Pringle E.G.
- Prist P.
- Prudente B.D.S.
- Puker A.
- Pérez-Mayorga M.A.
- Quaresma A.
- Queiroz A.C.M.
- Queiroz H.L.D.
- r Costa Neto S.V.D.
- Raseira M.B.
- Rechetelo J.
- Reis F.
- Reis L.P.
- Resende A.F.
- Resende A.F.
- Revilla J.D.C.
- Ribas C.R.
- Ribeiro J.M.F.
- Ribeiro R.A.B.
- Ribeiro S.C.
- Ribeiro S.P.
- Ribeiro V.S.
- Rodrigues D.D.J.
- Rodrigues S.B.
- Rodrigues T.H.A.
- Roque F.D.O.
- Rosa D.C.P.
- Rosalino L.M.D.C.
- Rousseau G.X.
- Ruschel A.
- Rutt C.L.
- s de Lima R.B.
- Salcedo A.K.M.
- Sales F.M.D.S.
- Salles F.F.
- Salomão R.P.
- Salomão R.P.
- Santana E.C.C.D.
- Santana F.D.
- Santiago W.T.V.
- Santos Ferreira V.R.
- Santos Neto C.R.D.
- Santos A.P.M.D.
- Santos B.B.
- Santos C.A.D.
- Santos C.R.M.D.
- Santos D.C.D.
- Santos E.A.D.
- Santos I.C.S.
- Santos J.C.
- Santos T.F.D.
- Sarmento P.S.D.M.
- Schietti J.
- Schietti J.
- Schmidt F.A.
- Schmidt F.A.
- Schwartz G.
- Schöngart J.
- Scudeller V.V.
- Shimabukuro Y.E.
- Shimano Y.
- Shutt J.
- Shutt J.
- Silva Brito J.
- Silva C.A.
- Silva C.V.J.
- Silva D.A.S.D.
- Silva D.R.D.
- Silva F.A.B.
- Silva J.O.D.A.
- Silva O.G.M.D.
- Silva R.D.C.
- Silva R.D.S.A.D.
- Silva R.J.D.
- Silva S.S.D.
- Silva T.S.F.
- Silva V.D.N.G.
- Silva W.C.D.
- Silva W.F.M.D.
- Silvano R.A.M.
- Silveira J.M.
- Silveira J.M.
- Silveira L.F.
- Silveira M.
- Silveira M.A.P.D.A.
- Silvério D.V.
- Simon M.F.
- Siqueira E.L.S.D.
- Solar R.
- Sousa S.A.D.
- Sousa T.
- Souto P.
- Souza F.K.S.D.
- Souza J.L.P.D.
- Souza M.F.D.
- Souza M.R.D.
- Souza P.
- Stegmann L.
- Stegmann L.
- Storck-Tonon D.
- Stropp J.
- Targhetta N.
- ter Steege H.
- ter Steege H.
- Todeschini F.
- Triana S.P.
- Uehara-Prado M.
- van den Berg E.
- Vasconcelos H.L.
- Vaz-de-Mello F.
- Vaz-de-Mello F.
- Vedovato L.B.
- Venticinque E.M.
- Venticinque E.M.
- Veras D.S.
- Vicente R.E.
- Vicentini A.
- Vidal E.
- Vieira D.L.M.
- Vieira I.C.G.
- Vieira I.C.G.
- Vieira L.
- Vieira S.A.
- Villa B.
- Vital M.J.S.
- Vulinec K.
- Wilker I.
- Williamson B.
- Wittmann F.
- Wolfe J.
- Yamamoto K.C.
- Zanetti R.
- Zanzini A.C.D.S.
- Zanzini L.P.
- Zuanon J.
- Zuanon J.
- Publication venue
- Elsevier
- Publication date
- 21/08/2023
- Field of study
Biodiversity loss is one of the main challenges of our time, and attempts to address it require a clear understanding of how ecological communities respond to environmental change across time and space. While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes, vast areas of the tropics remain understudied. In the American tropics, Amazonia stands out as the world's most diverse rainforest and the primary source of Neotropical biodiversity, but it remains among the least known forests in America and is often underrepresented in biodiversity databases. To worsen this situation, human-induced modifications may eliminate pieces of the Amazon's biodiversity puzzle before we can use them to understand how ecological communities are responding. To increase generalization and applicability of biodiversity knowledge, it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple organism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region's vulnerability to environmental change. 15%–18% of the most neglected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lost
The role of conditioning on heterosexual and homosexual partner preferences in rats
- Author
- Agmo A
- Aragona B.J
- Aragona B.J
- Bales K.L
- Balfour M.E
- Batenson P
- Becker J.B
- Beery A.K
- Berridge K.C
- Bielsky I.F
- Calcagnetti D.J
- Carmichael M.S
- Carter C.S
- Carter C.S
- Carter C.S
- Coria-Avila G.A
- Coria-Avila G.A
- Coria-Avila G.A
- Coria-Avila G.A
- Coria-Avila G.A
- Coria-Avila G.A
- Coria-Avila G.A
- Cushing B.S
- Der-Avakian A
- DeVries A.C
- Einon D.F
- Fillion T.J
- Garcia-Horsman S.P
- Getz L.L
- Gingrich B
- Graham J.M
- Insel T.R
- Insel T.R
- Insel T.R
- Ismail N
- Kendrick K.M
- Kippin T.E
- Kippin T.E
- Kippin T.E
- Lim M.M
- Lim M.M
- Liu Y
- Liu Y
- Luo S
- Malina R.M
- Namnyak M
- Panksepp J
- Parada M
- Paredes R.G
- Paredes R.G
- Paredes R.G
- Paredes-Ramos P
- Pavlov I
- Penn D
- Pfaus J.G
- Pfaus J.G
- Pfaus J.G
- Pfaus J.G
- Rouge-Pont F
- Salces I
- Schultz W
- Schultz W
- Skinner B.F
- Skinner B.F
- Tauber M
- Triana-Del Rio R
- van Furth W.R
- Wang Z
- Wang Z
- Williams J.R
- Winslow J.T
- Yamazaki K
- Young L.J
- Young L.J
- Publication venue
- 'Co-Action Publishing'
- Publication date
- Field of study
Large expert-curated database for benchmarking document similarity detection in biomedical literature search
- Publication venue
- 'Oxford University Press (OUP)'
- Publication date
- 01/01/2019
- Field of study
Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical science. © The Author(s) 2019. Published by Oxford University Press
Vorapaxar in the secondary prevention of atherothrombotic events
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- V. Silva
- V. Singh
- V. Stan
- V. Stedham
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- V. Toyota
- V.H. Hansen
- V.L. Laet
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- V.V. Bonarjee
- V.V. Nilsen
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- W. Palasik
- W. Penny
- W. Pluta
- W. Rogers
- W. Sobiczewski
- W. Staszkiewicz
- W. Stueflotten
- W. Sturm
- W. Szybka
- W. Van Landegem
- W. Zwinnen
- W.B. Campbell
- W.D. Doty
- W.G. Carlini
- W.P. Klinke
- W.P. McGuinn
- W.R. Ardito
- W.R. Cashion
- W.W. Wilson
- X. Garcia-Moll
- X. Liu
- Y. Aladro Benito
- Y. Chandrashekhar
- Y. Cottin
- Y. Feldman
- Y. Hirano
- Y. Hiraoka
- Y. Honda
- Y. Lampl
- Y. Manabe
- Y. Niinuma
- Y. Okada
- Y. Oono
- Y. Pesant
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- Y.K. Chan
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- Z. Bednarkiewicz
- Z. Chmielak
- Z. Gasior
- Z. Kalita
- Z. Klimsa
- Z. Kornacewicz-Jach
- Z. Lorenc
- Z. Mohamed
- Z. Monhart
- Publication venue
- 'Massachusetts Medical Society'
- Publication date
- 01/01/2012
- Field of study
Item does not contain fulltextBACKGROUND: Thrombin potently activates platelets through the protease-activated receptor PAR-1. Vorapaxar is a novel antiplatelet agent that selectively inhibits the cellular actions of thrombin through antagonism of PAR-1. METHODS: We randomly assigned 26,449 patients who had a history of myocardial infarction, ischemic stroke, or peripheral arterial disease to receive vorapaxar (2.5 mg daily) or matching placebo and followed them for a median of 30 months. The primary efficacy end point was the composite of death from cardiovascular causes, myocardial infarction, or stroke. After 2 years, the data and safety monitoring board recommended discontinuation of the study treatment in patients with a history of stroke owing to the risk of intracranial hemorrhage. RESULTS: At 3 years, the primary end point had occurred in 1028 patients (9.3%) in the vorapaxar group and in 1176 patients (10.5%) in the placebo group (hazard ratio for the vorapaxar group, 0.87; 95% confidence interval [CI], 0.80 to 0.94; P<0.001). Cardiovascular death, myocardial infarction, stroke, or recurrent ischemia leading to revascularization occurred in 1259 patients (11.2%) in the vorapaxar group and 1417 patients (12.4%) in the placebo group (hazard ratio, 0.88; 95% CI, 0.82 to 0.95; P=0.001). Moderate or severe bleeding occurred in 4.2% of patients who received vorapaxar and 2.5% of those who received placebo (hazard ratio, 1.66; 95% CI, 1.43 to 1.93; P<0.001). There was an increase in the rate of intracranial hemorrhage in the vorapaxar group (1.0%, vs. 0.5% in the placebo group; P<0.001). CONCLUSIONS: Inhibition of PAR-1 with vorapaxar reduced the risk of cardiovascular death or ischemic events in patients with stable atherosclerosis who were receiving standard therapy. However, it increased the risk of moderate or severe bleeding, including intracranial hemorrhage. (Funded by Merck; TRA 2P-TIMI 50 ClinicalTrials.gov number, NCT00526474.)