Título: | Effects of alirocumab on cardiovascular and metabolic outcomes after acute coronary syndrome in patients with or without diabetes: a prespecified analysis of the ODYSSEY OUTCOMES randomised controlled trial |
Autor(es): | RAY, Kausik K.; COLHOUN, Helen M.; SZAREK, Michael; BACCARA-DINET, Marie; BHATT, Deepak L.; BITTNER, Vera A.; BUDAJ, Andrzej J.; DIAZ, Rafael; GOODMAN, Shaun G.; HANOTIN, Corinne; HARRINGTON, Robert A.; JUKEMA, J. Wouter; LOIZEAU, Virginie; LOPES, Renato D.; MORYUSEF, Angele; MURIN, Jan; PORDY, Robert; RISTIC, Arsen D.; ROE, Matthew T.; TUNON, Jose; WHITE, Harvey D.; ZEIHER, Andreas M.; SCHWARTZ, Gregory S.; STEG, Philippe Gabriel; SCHWARTZ, Gregory G.; STEG, Ph. Gabriel; BHATT, Deepak L.; BITTNER, Vera A.; DIAZ, Rafael; GOODMAN, Shaun G.; HARRINGTON, Robert A.; JUKEMA, J. Wouter; SZAREK, Michael; ZEIHER, Andreas M.; TRICOCI, Pierluigi; ROE, Matthew T.; MAHAFFEY, Kenneth W.; EDELBERG, Jay M.; HANOTIN, Corinne; LECORPS, Guillaume; MORYUSEF, Angele; PORDY, Robert; SASIELA, William J.; TAMBY, Jean-Francois; AYLWARD, Philip E.; DREXEL, Heinz; SINNAEVE, Peter; DILIC, Mirza; GOTCHEVA, Nina N.; GOODMAN, Shaun G.; PRIETO, Juan-Carlos; YONG, Huo; LOPEZ-JARAMILLO, Patricio; PECIN, Ivan; REINER, Zeljko; OSTADAL, Petr; POULSEN, Steen Hvitfeldt; VIIGIMAA, Margus; NIEMINEN, Markku S.; DANCHIN, Nicolas; CHUMBURIDZE, Vakhtang; MARX, Nikolaus; LIBEROPOULOS, Evangelos; VALDOVINOS, Pablo Carlos Montenegro; TSE, Hung-Fat; KISS, Robert Gabor; XAVIER, Denis; ZAHGER, Doron; VALGIMIGLI, Marco; KIMURA, Takeshi; KIM, Hyo Soo; KIM, Sang-Hyun; KEDEV, Sasko; ERGLIS, Andrejs; LAUCEVICIUS, Aleksandras; YUSOFF, Khalid; LOPEZ, Ramos; LOPEZ, Gabriel Arturo Ramos; ALINGS, Marco; HALVORSEN, Sigrun; FLORES, Roger M. Correa; SY, Rody G.; BUDAJ, Andrzej; MORAIS, Joao; DOROBANTU, Maria; KARPOV, Yuri; RISTIC, Arsen D.; CHUA, Terrance; MURIN, Jan; FRAS, Zlatko; DALBY, Anthony J.; TUNON, Jose; SILVA, H. Asita de; HAGSTROM, Emil; MULLER, Christian; CHIANG, Chern-En; SRITARA, Piyamitr; GUNERI, Sema; PARKHOMENKO, Alexander; RAY, Kausik K.; MORIARTY, Patrick M.; ROE, Matthew T.; CHAITMAN, Bernard; KELSEY, Sheryl F.; OLSSON, Anders G.; ROULEAU, Jean-Lucien; SIMOONS, Maarten L.; ALEXANDER, Karen; MELONI, Chiara; ROSENSON, Robert; SIJBRANDS, Eric J. G.; ALEXANDER, John H.; ARMAGANIJAN, Luciana; BAGAI, Akshay; BAHIT, Maria Cecilia; BRENNAN, J. Matthew; CLIFTON, Shaun; DEVORE, Adam D.; DELOATCH, Shalonda; DICKEY, Sheila; DOMBROWSKI, Keith; DUCROCQ, Gregory; EAPEN, Zubin; ENDSLEY, Patricia; EPPINGER, Arleen; HARRISON, Robert W.; HESS, Connie Ng; HLATKY, Mark A.; JORDAN, Joseph Dedrick; KNOWLES, Joshua W.; KOLLS, Bradley J.; KONG, David F.; LEONARDI, Sergio; LILLIS, Linda; MARON, David J.; MARCUS, Jill; MATHEWS, Robin; MEHTA, Rajendra H.; MENTZ, Robert J.; MOREIRA, Humberto Graner; PATEL, Chetan B.; PEREIRA, Sabrina Bernardez; PERKINS, Lynn; POVSIC, Thomas J.; PUYMIRAT, Etienne; JONES, William Schuyler; SHAH, Bimal R.; SHERWOOD, Matthew W.; STRINGFELLOW, Kenya; SUJJAVANICH, Darin; TOMA, Mustafa; DIEPEN, Sean F. P. Van; WILSON, Matthew D.; YAN, Andrew Tze-Kay; LOPES, Renato D.; TROTTER, Charlene; SCHIAVI, Lilia B.; GARRIDO, Marcelo; ALVARISQUETA, Andres F.; SASSONE, Sonia A.; BORDONAVA, Anselmo P.; LIMA, Alberto E. Alves De; SCHMIDBERG, Jorge M.; DURONTO, Ernesto A.; CARUSO, Orlando C.; NOVARETTO, Leonardo P.; HOMINAL, Miguel Angel; MONTANA, Oscar R.; CACCAVO, Alberto; VILAMAJO, Oscar A. Gomez; LORENZATTI, Alberto J.; CARTASEGNA, Luis R.; PATERLINI, Gustavo A.; MACKINNON, Ignacio J.; CAIME, Guillermo D.; AMUCHASTEGUI, Marcos; SALOMONE, Rodolfo; CODUTTI, Oscar R.; JURE, Horacio O.; BONO, Julio O. E.; HRABAR, Adrian D.; VALLEJOS, Julio A.; GUERRERO, Rodolfo A. Ahuad; NOVOA, Federico; PATOCCHI, Cristian A.; ZAIDMAN, Cesar J.; GIULIANO, Maria E.; DRAN, Ricardo D.; VICO, Marisa L.; CARNERO, Gabriela S.; GUZMAN, Pablo N.; ALLENDE, Juan C. Medrano; BRASCA, Daniela F. Garcia; LABARTA, Miguel H. Bustamante; NANI, Sebastian; BLUMBERG, Eduardo D. S.; COLOMBO, Hugo R.; LIBERMAN, Alberto; LUCIARDI, Hector L.; WAISMAN, Gabriel D.; BERLI, Mario A.; DURAN, Ruben O. Garcia; CESTARI, Horacio G.; LUQUEZ, Hugo A.; GIORDANO, Jorge A.; SAAVEDRA, Silvia S.; ZAPATA, Gerardo; COSTAMAGNA, Osvaldo; LLOIS, Susana; WAITES, Jonathon H.; COLLINS, Nicholas; SOWARD, Allan; AYLWARD, Philip E.; HII, Chris L. S.; SHAW, James; ARSTALL, Margaret A.; HOROWITZ, John; ROGERS, James F.; COLQUHOUN, David; FLORES, Romulo E. Oqueli; ROBERTS-THOMSON, Philip; RAFFEL, Owen; LEHMAN, Sam J.; ARONEY, Constantine; COVERDALE, Steven G. M.; GARRAHY, Paul J.; STARMER, Gregory; SADER, Mark; CARROLL, Patrick A.; DICK, Ronald; ZWEIKER, Robert; HOPPE, Uta; HUBER, Kurt; BERGER, Rudolf; WEIDINGER, Franz; FAES, Dirk; HERMANS, Kurt; PIRENNE, Bruno; LEONE, Attilio; HOFFER, Etienne; VROLIX, Mathias C. M.; WOLF, Luc De; WOLLAERT, Bart; CASTADOT, Marc; DUJARDIN, Karl; BEAULOYE, Christophe; VERVOORT, Geert; STRIEKWOLD, Harry; CONVENS, Carl; ROOSEN, John; BARBATO, Emanuele; CLAEYS, Marc; COOLS, Frank; TERZIC, Ibrahim; BARAKOVIC, Fahir; MIDZIC, Zlatko; POJSKIC, Belma; FAZLIBEGOVIC, Emir; DURAK-NALBANTIC, Azra; VULIC, Dusko; MUSLIBEGOVIC, Adis; GORONJA, Boris; REIS, Gilmar; SOUSA, Luciano; NICOLAU, Jose C.; GIORGETO, Flavio E.; SILVA, Ricardo P.; MAIA, Lilia Nigro; RECH, Rafael; ROSSI, Paulo R. F.; CERQUEIRA, Maria Jose A. G.; DUDA, Norberto; KALIL, Renato; KORMANN, Adrian; ABRANTES, Jose Antonio M.; PIMENTEL FILHO, Pedro; SOGGIA, Ana Priscila; SANTOS, Mayler O. N. de; NEUENSCHWANDER, Fernando; BODANESE, Luiz C.; MICHALAROS, Yorghos L.; ELIASCHEWITZ, Freddy G.; VIDOTTI, Maria H.; LEAES, Paulo E.; BOTELHO, Roberto V.; KAISER, Sergio; MANENTI, Euler Roberto F. Fernandes; PRECOMA, Dalton B.; JORGE, Jose C. Moura; SILVA, Pedro G. M. de B.; SILVEIRA, Jose A.; SAPORITO, Wladmir; MARIN NETO, Jose A.; FEITOSA, Gilson S.; RITT, Luiz Eduardo F.; SOUZA, Juliana A. de; COSTA, Fernando; SOUZA, Weimar K. S. B.; REIS, Helder J. L.; MACHADO, Leandro; AYOUB, Jose Carlos Aidar; TODOROV, Georgi V.; NIKOLOV, Fedya P.; VELCHEVA, Elena S.; TZEKOVA, Maria L.; BENOV, Haralambi O.; PETRANOV, Stanislav L.; TUMBEV, Haralin S.; SHEHOVA-YANKOVA, Nina S.; MARKOV, Dimitar T.; RAEV, Dimitar H.; MOLLOV, Mihail N.; KICHUKOV, Kostadin N.; ILIEVA-PANDEVA, Katya A.; IVANOVA, Raya; MINCHEVA, Valentina M.; LAZOV, Petar V.; DIMOV, Bojidar I.; SENARATNE, Manohara; STONE, James; KORNDER, Jan; PEARCE, Stephen; DION, Danielle; SAVARD, Daniel; PESANT, Yves; PANDEY, Amritanshu; ROBINSON, Simon; GOSSELIN, Gilbert; VIZEL, Saul; HOAG, Gordon; BOURGEOIS, Ronald; MORISSET, Anne; SABBAH, Eric; SUSSEX, Bruce; KOUZ, Simon; MACDONALD, Paul; DIAZ, Ariel; MICHAUD, Nicolas; FELL, David; LEUNG, Raymond; VUURMANS, Tycho; LAI, Christopher; NIGRO, Frank; DAVIES, Richard; NOGAREDA, Gustavo; VIJAYARAGHAVAN, Ram; DUCAS, John; LEPAGE, Serge; MEHTA, Shamir; CHA, James; DUPUIS, Robert; FONG, Peter; RODES-CABAU, Josep; FADLALLAH, Hussein; CLEVELAND, David; Thao Huynh; BATA, Iqbal; HAMEED, Adnan; PINCETTI, Cristian; POTTHOFF, Sergio; PRIETO, Juan C.; ACEVEDO, Monica; AGUIRRE, Arnoldo; VEJAR, Margarita; YANEZ, Mario; ARANEDA, Guillermo; FERNANDEZ, Mauricio; PEREZ, Luis; VARLETA, Paola; FLORENZANO, Fernando; HUIDOBRO, Laura; RAFFO, Carlos A.; OLIVARES, Claudia; NAHUELPAN, Leonardo; MONTECINOS, Humberto; CHEN, Jiyan; DONG, Yugang; HUANG, Weijian; WANG, Jianzhong; HUANG, Shi'An; YAO, Zhuhua; LI, Xiang; CUI, Lan; LIN, Wenhua; SUN, Yuemin; WANG, Jingfeng; LI, Jianping; ZHANG, Xuelian; ZHU, Hong; CHEN, Dandan; HUANG, Lan; DONG, Shaohong; SU, Guohai; XU, Biao; SU, Xi; CHENG, Xiaoshu; LIN, Jinxiu; ZONG, Wenxia; LI, Huanming; FENG, Yi; XU, Dingli; YANG, Xinchun; KE, Yuannan; LIN, Xuefeng; ZHANG, Zheng; ZHENG, Zeqi; LUO, Zhurong; CHEN, Yundai; DING, Chunhua; ZHENG, Yang; LI, Xiaodong; PENG, Daoquan; LI, Ying; WEI, Meng; LIU, Shaowen; YU, Yihua; QU, Baiming; JIANG, Weihong; ZHOU, Yujie; ZHAO, Xingsheng; YUAN, Zuyi; GUO, Ying; XU, Xiping; SHI, Xubo; GE, Junbo; FU, Guosheng; BAI, Feng; FANG, Weiyi; SHOU, Xiling; YANG, Xiangjun; WANG, Jian'An; SUN, Yingxian; LU, Qinghua; ZHANG, Ruiyan; ZHU, Jianhua; XU, Yizhou; FAN, Zhongcai; LI, Tianchang; WU, Chun; JARAMILLO, Nicolas; VALLEJO, Gregorio Sanchez; BOTIA, Diana C. Luna; LOPEZ, Rodrigo Botero; SALAZAR, Dora I. Molina De; BONFANTI, Alberto J. Cadena; HIGUERA, Juan Diego; SILVA, Sandra I. Barrera; LOZADA, Henry J. Garcia; ARROYO, Julian A. Coronel; MENDOZA, Jose L. Accini; RUIZ, Ricardo L. Fernandez; JATIN, Fernando G. Manzur; HERAZO, Aristides Sotomayor; PARADA, Jeffrey Castellanos; TRIANA, Miguel A. Urina; STROZZI, Maja; CAR, Sinisa; MILICIC, Davor; BENCIC, Martina Lovric; PINTARIC, Hrvoje; PRVULOVIC, Deiti; SIKIC, Jozica; PERSIC, Viktor; MILETA, Dean; STAMBUK, Kresimir; ZDRAVKO, Babic; TOMULIC, Vjekoslav; KRSTULOVIC, Stanka Mejic; STARCEVIC, Boris; SPINAR, Jindrich; HORAK, David; STASEK, Josef; ALAN, David; MACHOVA, Vilma; LINHART, Ales; NOVOTNY, Vojtech; KAUCAK, Vladimir; ROKYTA, Richard; NAPLAVA, Robert; COUFAL, Zdenek; ADAMKOVA, Vera; PODPERA, Ivo; ZIZKA, Jiri; MOTOVSKA, Zuzana; MARUSINCOVA, Ivana; SVAB, Premysl; OSTADAL, Petr; HEINC, Petr; KUCHAR, Jiri; POVOLNY, Petr; MATUSKA, Jiri; RAUNGAARD, Bent; CLEMMENSEN, Peter; BANG, Lia E.; MAY, Ole; BOTTCHER, Morten; HOVE, Jens D.; FROST, Lars; GISLASON, Gunnar; LARSEN, John; JOHANSEN, Peter Betton; HALD, Flemming; JEPPESEN, Jorgen; NIELSEN, Tonny; KRISTENSEN, Kjeld S.; WALICHIEWICZ, Piotr Maria; LOMHOLDT, Jens D.; KLAUSEN, Ib C.; NIELSEN, Peter Kaiser; DAVIDSEN, Flemming; VIDEBAEK, Lars; SOOTS, Mai; VAHULA, Veiko; HEDMAN, Anu; SOOPOLD, Ullar; MARTSIN, Kaja; KRISTJAN, Arved; TASKINEN, Marja-Riitta; PORTHAN, Kimmo; AIRAKSINEN, Juhani K.; JUONALA, Markus; KIVINIEMI, Tuomas; VIKMAN, Saila; POSIO, Pirjo; TAURIO, Jyrki; HUIKURI, Heikki; KAIKKONEN, Kari; COSTE, Pierre; FERRARI, Emile; MOREL, Olivier; MONTALESCOT, Gilles; BARONE-ROCHETTE, Gilles; MANSOURATI, Jacques; COTTIN, Yves; LECLERCQ, Florence; BELHASSANE, Abdelkader; DELARCHE, Nicolas; BOCCARA, Franck; PAGANELLI, Franck; CLERC, Jerome; SCHIELE, Francois; ABOYANS, Victor; PROBST, Vincent; BERLAND, Jacques; LEFEVRE, Thierry; CITRON, Bernard; KHINTIBIDZE, Irakli; SHABURISHVILI, Tamaz; PAGAVA, Zurab; GHLONTI, Ramaz; LOMINADZE, Zaza; KHABEISHVILI, George; HEMETSBERGER, Rayyan; RAUCH-KROEHNERT, Ursula; STRATMANN, Matthias; APPEL, Karl-Friedrich; SCHMIDT, Ekkehard; OMRAN, Heyder; STELLBRINK, Christoph; DORSEL, Thomas; LIANOPOULOS, Emmanouil; MARX, Roger; ZIRLIK, Andreas; SCHELLENBERG, Detlev; HEITZER, Thomas; LAUFS, Ulrich; MARX, Nikolaus; GIELEN, Stephan; WINKELMANN, Bernhard; BEHRENS, Steffen; SYDOW, Karsten; SIMONIS, Gregor; MUENZEL, Thomas; WERNER, Nikos; LEGGEWIE, Stefan; BOECKER, Dirk; BRAUN-DULLAEUS, Ruediger; TOURSARKISSIAN, Nicole; JESERICH, Michael; WEISSBRODT, Matthias; SCHAEUFELE, Tim; WEIL, Joachim; VOELLER, Heinz; WALTENBERGER, Johannes; NATOUR, Mohammed; SCHMITT, Susanne; STEINER, Stephan; HEIDENREICH, Lothar; GREMMLER, Uwe; KILLAT, Holger; RIEKER, Werner; PATSILINAKOS, Sotiris; KARTALIS, Athanasios; MANOLIS, Athanassios; SIONIS, Dimitrios; LIBEROPOULOS, Evangelos; SKOUMAS, Ioannis; ATHYROS, Vasilios; VARDAS, Panagiotis; PARTHENAKIS, Frangkiskos; ALEXOPOULOS, Dimitrios; HAHALIS, Georgios; LEKAKIS, John; HATZITOLIOS, Apostolos; OVANDO, Sergio R. Fausto; VALDOVINOS, Pablo Carlos Montenegro; BENECKE, Juan L. Arango; LEON, Edgar R. Rodriguez De; YAN, Bryan P. Y.; SIU, David C. W.; TURI, Tibor; MERKELY, Bela; KISS, Robert Gabor; UNGI, Imre; LUPKOVICS, Geza; NAGY, Lajos; KATONA, Andras; EDES, Istvan; MULLER, Gabor; HORVATH, Ivan; KAPIN, Tibor; FALUKOZY, Jozsef; KUMBLA, Mukund; SANDHU, Manjinder; ANNAM, Sharath; PRODDUTUR, Naveen Reddy; PREMCHAND, Rajendra K.; MAHAJAN, Ajaykumar; ABHYANAKAR, Atul D.; KERKAR, Prafulla; GOVINDA, Ravishankar A.; OOMMAN, Abraham; SINHA, Dhurjati; PATIL, Sachin N.; KAHALI, Dhiman; SAWHNEY, Jitendra; JOSHI, Abhijeet B.; CHAUDHARY, Sanjeev; HARKUT, Pankaj; GUHA, Santanu; PORWAL, Sanjay; JUJJURU, Srimannarayana; POTHINENI, Ramesh B.; MONTEIRO, Minguel R.; KHAN, Aziz; IYENGAR, Shamanna S.; GREWAL, Jasprakash Singh; CHOPDA, Manoj; FULWANI, Mahesh C.; PATANGE, Aparna; CHOPRA, Vijay K.; GOYAL, Naresh K.; SHINDE, Rituparna; MANAKSHE, Gajendra V.; PATKI, Nitin; SETHI, Sumeet; MUNUSAMY, Vengatesh; KARNA, Sunil; ADHYAPAK, Srilakshmi; PANDURANGI, Ulhas; MATHUR, Rishabh; KALASHETTI, Suhas; BHAGWAT, Ajit; RAGHURAMAN, Bagirath; YERRA, Shiv Kumar; BHANSALI, Prasant; BORSE, Rohidas; DAS, Srihari; ABDULLAKUTTY, Jabir; SAATHE, Shireesh; PALIMKAR, Priya; ABDULLKUTTY, Jabir; SATHE, Shireesh; PALIMKAR, Priya; ATAR, Shaul; SHECHTER, Michael; MOSSERI, Morris; ARBEL, Yaron; LOTAN, Chaim; ROSENSCHEIN, Uri; KATZ, Amos; HENKIN, Yaakov; FRANCIS, Adi; KLUTSTEIN, Marc; NIKOLSKY, Eugenia; TURGEMAN, Yoav; HALABI, Majdi; KORNOWSKI, Ran; JONAS, Michael; AMIR, Offer; ROZENMAN, Yoseph; FUCHS, Shmuel; HUSSEIN, Osamah; GAVISH, Dov; VERED, Zvi; CARACO, Yoseph; ELIAS, Mazen; TOV, Naveh; LISHNER, Michael; ELIAS, Nizar; PIOVACCARI, Giancarlo; PELLEGRIN, Annamaria De; GUARDIGLI, Gabriele; LICCIARDELLO, Giovanni; AUGUADRO, Carla; CUCCIA, Claudio; SALVIONI, Alessandro; MUSUMECI, Giuseppe; CALABRO, Paolo; NOVO, Salvatore; FAGGIANO, Pompilio; CESARE, Nicoletta B. De; BERTI, Sergio; CAVALLINI, Claudio; PUCCIONI, Enrico; GALVANI, Marcello; TESPILI, Maurizio; PIATTI, Piermarco; PALVARINI, Michela; LUCA, Giuseppe De; VIOLINI, Roberto; LEO, Alessandro De; FILARDI, Pasquale Perrone; FERRATINI, Maurizio; RICCA, Vittorio; DAI, Kazuoki; KAMIYA, Haruo; ANDO, Kenji; TAKEDA, Yoshihiro; MORINO, Yoshihiro; HATA, Yoshiki; KIMURA, Kazuo; KISHI, Koichi; MICHISHITA, Ichiro; UEHARA, Hiroki; HIGASHIKATA, Toshinori; HIRAYAMA, Atsushi; HIROOKA, Keiji; SAKAGAMI, Satoru; TAGUCHI, Shuichi; KOIKE, Akihiro; FUJINAGA, Hiroyuki; KOBA, Shinji; KOZUMA, Ken; KAWASAKI, Tomohiro; ONO, Yujiro; SHIMIZU, Masatoshi; KATSUDA, Yousuke; WADA, Atsuyuki; SHINKE, Toshiro; KIMURA, Takeshi; AKO, Junya; FUJII, Kenshi; TAKAHASHI, Toshiyuki; SAKAMOTO, Tomohiro; FURUKAWA, Yutaka; SUGINO, Hiroshi; MANO, Toshiaki; UTSU, Noriaki; ITO, Kashima; HARAGUCHI, Takuya; UEDA, Yasunori; NISHIBE, Akira; FUJIMOTO, Kazuteru; MASUTANI, Motomaru; FUJIMOTO, Kazuteru; YOON, Jung Han; KIM, Sang-Hyun; PARK, Hun Sik; CHAE, In-Ho; KIM, Moo Hyun; JEONG, Myung Ho; RHA, Seungwoon; KIM, Chongjin; KIM, Hyo-Soo; HONG, Taekjong; TAHK, Seung-Jea; KIM, Youngkwon; BUSMANE, Arija; PONTAGA, Natalija; STRELNIEKS, Aldis; MINTALE, Iveta; SIME, Iveta; PETRULIONIENE, Zaneta; KAVALIAUSKIENE, Roma; JURGAITIENE, Ruta; SAKALYTE, Gintare; SLAPIKAS, Rimvydas; NORKIENE, Sigute; MISONIS, Nerijus; KIBARSKIS, Aleksandras; KUBILIUS, Raimondas; BOJOVSKI, Stojko; KEDEV, Sasko; LOZANCE, Nensi; KJOVKAROSKI, Aleksandar; DONCOVSKA, Snezana; ONG, Tiong Kiam; KASIM, Sazzli; MASKON, Oteh; KANDASAMY, Balachandran; YUSOFF, Khalid; LIEW, Houng B.; MOHAMED, Wan Mohd Izani Wan; CASTILLO, Armando Garcia; CALVILLO, Jorge Carrillo; CAMPOS, Pedro Fajardo; FRAGOSO, Juan Carlos Nunez; LLAMAS, Edmundo Alfredo Bayram; GAMBA, Marco Antonio Alcocer; MADRIGAL, Jaime Carranza; SALAS, Luis Gerardo Gonzalez; ROSAS, Enrique Lopez; DIAZ, Belinda Gonzalez; VAZQUEZ, Eduardo Salcido; ACKAR, Alfredo Nacoud; ESPERON, Guillermo Antonio Llamas; SANCHEZ, Carlos Rodolfo Martinez; LEON, Maria Guerrero De; OTERO, Rodrigo Suarez; SALMON, Guillermo Fanghanel; RIOS, Jesus Antonio Perez; RUIZ, Jose Angel Garza; BREEDVELD, Robert W.; HOOGSLAG, Pieter A. M.; SURYAPRANATA, Harry; OOMEN, Antonius; WIERSMA, Jacobijne J.; WAL, Ruud M. A. Van Der; HUYSDUYNEN-MONRAATS, Pascalle S. Hooft Van; KARALIS, Ioannis; VERDEL, Gerardus J. E.; BRUEREN, Bart R. G.; TROQUAY, Roland PTh; VIERGEVER, Eric P.; AL-WINDY, Nadea Y. Y.; BARTELS, Gerard L.; CORNEL, Jan H.; HERMANS, Walter R. M.; HERRMAN, Johannes P. R.; BOS, Robert J.; GROUTARS, Reginald G. E. J.; ZWAAN, Coenraad C. Van Der; KAPLAN, Refik; RONNER, Eelko; GROENEMEIJER, Bjorn E.; BRONZWAER, Patrick N. A.; LIEM, Anho A. H.; RENSING, Bernard J. W. M.; BOKERN, Marcel J. J. A.; NIJMEIJER, Remco; HERSBACH, Ferry M. R. J.; WILLEMS, Frank F.; GOSSELINK, Antonius T. M.; ELLIOTT, John; WILKINS, Gerard; FISHER, Raewyn; SCOTT, Douglas; HART, Hamish; STEWART, Ralph; HARDING, Scott; TERNOUTH, Ian; FISHER, Nicholas; AITKEN, Denise; ANSCOMBE, Russell; DAVIDSON, Laura; TOMALA, Tadeusz; NYGARD, Ottar; SPARBY, Jon Arne; ANDERSEN, Kjell; GULLESTAD, Lars; JORTVEIT, Jarle; MUNK, Peter S.; SINGSAAS, Erlend Gyllensten; HALVORSEN, Sigrun; HURTIG, Ulf; FLORES, Roger M. Correa; TICONA, Jorge R. Calderon; VELASQUEZ, Julio R. Durand; MIGUEL, Sandra A. Negron; PEREZ, Enrique S. Sanabria; CHAMBILLA, Jesus M. Carrion; AYALA, Carlos A. Chavez; LEON, Reynaldo P. Castillo; GONZALES, Rolando J. Vargas; ZUNIGA, Jose D. Hernandez; COSAVALENTE, Luis A. Camacho; MANNUCCI, Jorge E. Bravo; LANDEO, Javier Heredia; NAVARRO, Nassip C. Llerena; CONCHA, Yudy M. Roldan; CHAVEZ, V-ctor E. Rodriguez; HERNANDEZ, Henry A. Anchante; NUNEZ, Carlos A. Zea; RAMOS, Walter Mogrovejo; FERROLINO, Arthur; SY, Rosa Allyn G.; TIRADOR, Louie; SY, Rody G.; MATIGA, Generoso; COCHING, Raul Martin; BERNAN, Alisa; ROGELIO, Gregorio; MORALES, Dante D.; TAN, Edgar; SULIT, Dennis Jose; WLODARCZAK, Adrian; JAWORSKA, Krystyna; SKONIECZNY, Grzegorz; PAWLOWICZ, Lidia; WOJEWOD, Pawel; BUSZ-PAPIEZ, Benita; BEDNARSKI, Janusz; GOCH, Aleksander; STANETA, Pawel; DULAK, Elzbieta; BUDAJ, Andrzej; SAMINSK, Krzysztof; KRASOWSKI, Wlodzimierz; SUDNIK, Wanda; ZURAKOWSKI, Aleksander; SKORSKI, Marcin; LYSEK, Roman; MIKLASZEWICZ, Beata; KUBICA, Jacek; LIPKO, Jan Andrzej; KOSTARSKA-SROKOSZ, Edyta; PIEPIORKA, Marek; DRZEWIECKA, Anna; SCIBORSKI, Ryszard; STASIEWSKI, Arkadiusz; BLICHARSKI, Tomasz; BYSTRYK, Leszek; SZPAJER, Michal; KOROL, Marek; CZERSKI, Tomasz; MIREK-BRYNIARSKA, Ewa; GNIOT, Jacek; LUBINSKI, Andrzej; GORNY, Jerzy; FRANEK, Edward; RACZAK, Grzegorz; SZWED, Hanna; MONTEIRO, Pedro; BASTOS, Jose Mesquita; PEREIRA, Helder H.; MARTINS, Dinis; MORAIS, Joao; SEIXO, Filipe; MENDONCA, Carlos; BOTELHO, Ana; MINESCU, Bogdan; ISTRATOAIE, Octavian; TESLOIANU, Dan N.; DOROBANTU, Maria; CRISTIAN, Gabriel; PODOLEANU, Cristian G. C.; CONSTANTINESCU, Mircea C. 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Van; SEBASTIAN, Peter J.; PILLAY, Thayabran; SAAIMAN, Jan A.; COMMERFORD, Patrick J.; CASSIMJEE, Soraya; EBRAHIM, Iftikhar O.; SARVAN, Mahomed; MYNHARDT, Joseph H.; REUTER, Helmuth; MOODLEY, Rajendran; VIDA, Manuel; FILLAT, Angel R. Cequier; PERIS, Vicente Bodi; JIMENEZ, Francisco Fuentes; MARIN, Francisco; FERNANDEZ, Jose M. Cruz; GIL-EXTREMERA, Blas; DIZ, Fernando Worner; GARCIA-DORADO, David; INIGUEZ, Andres; FERNANDEZ, Jose Tunon; GONZALEZ-JUANATEY, Jose R.; PORTALES, Javier Fernandez; MURILLO, Fernando Civeira; PERICAS, Laia Matas; ZAMORANO, Jose Luis; MARTIN, Manuel De Mora; CORTADA, Jordi Bruguera; MARTIN, Joaquin J. Alonso; FERNANDEZ, Jose R. De Berrazueta; FERNANDEZ, Jose Francisco Diaz; LLEDO, Jose Alberto Garcia; SALES, Juan Cosin; RODRIGUEZ, Javier Botas; TRAGANT, Gabriel Gusi; BENEDICTO, Amparo; GONZALEZ-JUANATEY, Carlos; POTAU, Mercedes Camprubi; PEREZ, Ignacio Plaza; TASSA, Cesar Moris De La; RINCON, Pablo Loma-Osorio; RECENA, Javier Balaguer; ESCUDIER, Juan M.; PAYERAS, Antonio Coca; ORCAJO, Norberto Alonso; VALDIVIELSO, Pedro; CONSTANTINE, Godwin; HANIFFA, Ruvaiz; TISSERA, Nirmali; AMARASEKERA, Stanley; FERNANDO, Nimali; JAYAWARDENA, Jayanthimala; SANTHARAJ, Wijeyasingam; EKANAYAKA, Ruvan; MENDIS, Sepalika; SENARATNE, Vajira; MAYURATHAN, Gnanamoorthy; SIRISENA, Thilak; RAJAPAKSHA, Ajantha; HERATH, Jagath I.; AMARASENA, Naomali; BERGLUND, Stefan; RASMANIS, Gundars; WITT, Nils; MOURTZINIS, Georgios; NICOL, Peter; HANSEN, Ole; ROMEO, Stefano; JENSEN, Steen Agergaard; TORSTENSSON, Ingemar; AHREMARK, Ulf; SUNDELIN, Torbjorn; MOCCETTI, Tiziano; MULLER, Christian; MACH, Francois; BINDER, Ronald; TSAI, Wei-Chuan; UENG, Kwo-Chang; LAI, Wen-Ter; LIU, Ming-En; HWANG, Juey-Jen; YIN, Wei-Hsian; HSIEH, I-Chang; LIN, Wei Hsiang; KUO, Jen-Yuan; HUANG, Tsuei-Yuan; FANG, Chih-Yuan; KAEWSUWANNA, Pinij; SOONFUANG, Wasant; JINTAPAKORN, Woravut; SUKONTHASARN, Apichard; WONGPRAPARUT, Nattawut; SASTRAVAHA, Krisada; SANSANAYUDH, Nakarin; KEHASUKCHAROEN, Wirash; PIYAYOTAI, Dilok; CHOTNOPARATPAT, Paiboon; CAMSARI, Ahmet; KULTURSAY, Hakan; MUTLU, Bulent; ERSANLI, Murat; DEMIRTAS, Mustafa; KIRMA, Cevat; URAL, Ertan; KOLDAS, Lale; KARPENKO, Oleksandr; PROKHOROV, Alexander; VAKALUYK, Ihor; MYSHANYCH, Halyna; RESHOTKO, Dmytro; BATUSHKIN, Valeriy; RUDENKO, Leonid; KOVALSKYI, Ihor; KUSHNIR, Mykola; TSELUYKO, Vira; MOSTOVOY, Yuriy; STANISLAVCHUK, Mykola; KYIAK, Yulian; KARPENKO, Yuriy; MALYNOVSKY, Yaroslav; KLANTSA, Andriy; KUTNIY, Oles; AMOSOVA, Ekaterina; TASHCHUK, Viktor; LESHCHUK, Oleh; RISHKO, Mykola; KOPYTSYA, Mykola; YAGENSKY, Andriy; VATUTIN, Mykola; BAGRIY, Andriy; BARNA, Olga M.; USHAKOV, Olexiy; DZYAK, Georgiy; GOLOBORODKO, Borys; RUDENKO, Anatolii; ZHELEZNYY, Volodymyr; TREVELYAN, Jasper; ZAMAN, Azfar; LEE, Kaeng; MORIARTY, Andrew; AGGARWAL, Rajesh K.; CLIFFORD, Piers; WONG, Yuk-Ki; IQBAL, Syed M. R.; SUBKOVAS, Eduardas; BRAGANZA, Denise; SARKAR, David; STOREY, Robert; GRIFFITHS, Huw; MCCLURE, Sam; MUTHUSAMY, Rangasamy; KURIAN, John; LEVY, Terry; BARR, Craig; KADR, Honer; GERBER, Robert; SIMAITIS, Audrius; SORAN, Handrean; MATHUR, Anthony; BRODISON, Adrian; OLIVER, Richard; MUDAWI, Telal; REYNOLDS, Timothy; SHARMAN, David; BUTLER, Rob; WILKINSON, Peter; LIP, Gregory Y. H.; HALCOX, Julian; VARDI, Gil; BALDARI, Duccio; BRABHAM, David; II, Charles Treasure; DAHL, Charles; PALMER, Bruce; WISEMAN, Alan; KHAN, Abul; PURI, Sanjeev; MOHART, Ann Elizabeth; INCE, Carlos; FLORES, Enrique; WRIGHT, Scott; CHENG, Shi-Chi; ROSENBERG, Michael; ROGERS JR., William; KOSINSKI, Edward; FORGOSH, Les; WALTMAN, Jonathan; KHAN, Misal; SHOUKFEH, Mohammad; DAGHER, Georges; LIEBER, Ira; KUMAR, Priya; EAST, Cara; KRICHMAR, Perry; WHITE, Lindsey; KNICKELBINE, Thomas; HALDIS, Thomas; GILLESPIE, Eve; SUH, David; ARIF, Imran; AKHTER, Faiq; CARLSON, Eric; D'URSO, Michael; EL-AHDAB, Fadi; NELSON, William; HARRIS, Barry; COHEN, Steven; CARTER, Luther; SABATINO, Kenneth; HADDAD, Tariq; MALIK, Amir; RAO, Sunder; MULKAY, Angel; JOVIN, Ion; KLANCKE, Kim; MALHOTRA, Vinay; DEVARAPALLI, Sai K.; KOREN, Michael; CHANDNA, Harish; III, George Dodds; JANIK, Matthew; MORAN, Joseph; SUMNER, Andrew; KOBAYASHI, John; DAVIS, William; YAZDANI, Shahram; PASQUINI, John; THAKKAR, Maitreya; VEDERE, Amarnath; LEIMBACH, Wayne; RIDER, James; SINGH, Narendra; SHAH, Anil V.; JANOSIK, Denise; PEPINE, Carl; BERMAN, Brett; GELORMINI, Joseph; DANIELS, Christopher; KEATING, Friederike; KONDO, Nicholas I.; SHETTY, Sanjay; WAIDER, Winfried; TAKATA, Theodore; ABU-FADEL, Mazen; SHAH, Vipul; AGGARWAL, Rahul; IZZO, Mark; KUMAR, Anil; HATTLER, Brack; LINK, Chad; BORTNICK, Anna; III, George Kinzfogl; GHITIS, Arnold; LARRY, John; TEUFEL, Edward; KUHLMAN, Peter; MCLAURIN, Brent; ZHANG, Wenwu; THEW, Stephen; ABBAS, Jalal; WHITE, Matthew; RANADIVE, Nandkishore; GRING, Christian; HENDERSON, David; SCHUCHARD, Timothy; FARHAT, Naim; KLINE, Geoffrey; MAHAL, Sharan; WHITAKER, Jack; SPEIRS, Shawn; ANDERSEN, Rolf; DABOUL, Nizar; HORWITZ, Phillip; PONCE, George; JAFAR, Zubair; MCGARVEY JR., Joseph; PANCHAL, Vipul; VOYCE, Stephen; BLOK, Thomas; SHELDON, William; AZIZAD, Masoud M.; SCHMALFUSS, Carsten; PICONE, Mark; HERZOG JR., William; LINDSEY, Jason; NOWINS, Rosemary; LEPOR, Norman; SHAHAWY, Mahfouz El; WEINTRAUB, Howard; IRIMPEN, Anand; MAY, Wade; GALSKI, Thomas; CHU, Alan; MODY, Freny; HODES, Zachary; ROSE, Gregory; FAIRLAMB, James; LAMBERT JR., Charles; RAISINGHANI, Ajit; ABBATE, Antonio; KING, Marilyn; CAREY, Charles; GERBER, Jaime; YOUNIS, Liwa; PARK, Hyeun (Tom); VIDOVICH, Mladen; KNUTSON, Thomas; FRIEDMAN, Dennis; CHALEFF, Fred; LOUSSARARIAN, Arthur; ROZEMAN, Phillip; KIMMELSTIEL, Carey; SILVER, Kevin; FOSTER, Malcolm; TONNESSEN, Glen; AMLANI, Mohamadali; WALI, Andreas; MALOZZI, Christopher; WATTANAKIT, Keattiyoat; O'DONNELL, Philip J.; SINGAL, Dinesh; JAFFRANI, Naseem; BANURU, Sridhar; FISHER, Daniel; XENAKIS, Mark; PERLMUTTER, Neal; BHAGWAT, Ravi; STRADER JR., James; AKYEA-DJAMSON, Ayim; LABROO, Ajay; LEE, Kwan; MARAIS, H. John; CLAXTON JR., Edmund; BERK, Martin; ROSSI, Peter; JOSHI, Parag; KHAIRA, Ajit S.; KUMKUMIAN, Greg; LUPOVITCH, Steven; PUROW, Joshua; WELKA, Stephen; HOFFMAN, David; FISCHER, Stuart; SOROKA, Eugene; EAGERTON, Donald; PANCHOLY, Samir; RAY, Michael; FARRAR, Michael; POLLOCK, Stewart; FRENCH, William J.; DIAMANTIS, Steve; GIMPLE, Lawrence; NEUSTEL, Mark; SCHWARTZ, Steven; PEREIRA, Edward; SPRIGGS, Douglas; STRAIN, Janet; VO, Anthony; CHANE, Majed; HALL, Jason; VIJAY, Nampalli; LOTUN, Kapildeo; LESTER, F. Martin; NAHHAS, Ahed; POPE, Theodore; NAGER, Paul; VOHRA, Rakesh; BASHIR, Riyaz; AHMED, Hinan; BERLOWITZ, Michael; FISHBERG, Robert; BARRUCCO, Robert; YANG, Eric; RADIN, Michael; SPORN, Daniel; EISENBERG, Steven; LANDZBERG, Joel; MCGOUGH, Martin; TURK, Samir; SCHWARTZ, Michael; SUNDRAM, P. Sandy; JAIN, Diwakar; ZAINEA, Mark; BAYRON, Carlos; KARLSBERG, Ronald; LUI, Henry; KEEN, William; WESTERHAUSEN JR., Donald; KHURANA, Sandeep; AGARWAL, Himanshu; BIRCHEM, Jessica; PENNY JR., William; CHANG, Mark; MURPHY, Sherrill; MURPHY, Sherrill; SCHIFFERDECKER, Branislav; GILBERT, John M.; CHALAVARYA, Gopal; EATON, Charles; SCHMEDTJE JR., John F.; CHRISTENSON, Stuart; DENHAM, Douglas; MACDONELL, Alexander; GIBSON, Paul; RAHMAN, Aref; JOUNDI, Tammam Al; CONRAD, Gary; KOTHA, Purushotham; LOVE, Michael; GIESLER, Gregory; RUBENSTEIN, Howard; AKRIGHT, Laura; KRAWCZYK, Justine; WELLS, Terry; WELKER, James; FOSTER, Robert; GILMORE, Richard; ANDERSON, Jay; JACOBY, Douglas; HARRIS, Bill; GARDNER, Geraldine; DANDILLAYA, Ramprasad; VORA, Kishor; KOSTIS, John; HUNTER, John; LAXSON, David; BALL, Eric; CAMP, Alan; LOPES, Renato; EGYDIO, Flavia; KAWAKAMI, Anelise; OLIVEIRA, Janaina; WOZNIAK, Julianna; MATTHEWS, Alexander; RATKY, Caroline; VALIRIS, Janine; BERDAN, Lisa; HEPDITCH, Anita; QUINTERO, Kirby; RORICK, Tyrus; WESTBROOK, Melissa; PASCUAL, Andrea; ROVITO, Carla; BEZAULT, Madeleine; DROUET, Elodie; SIMON, Tabassome; ALSWEILER, Caroline; LUYTEN, Anne; AYLWARD, Phil; BUTTERS, Julie; GRIFFITH, Liddy; SHAW, Michelle; HAGSTROM, Emil; GRUNBERG, Lena; ISLAM, Shahidul; BREGEAULT, Marie-France; BOUGON, Nathalie; FAUSTINO, Douglas; FONTECAVE, Sylvie; MURPHY, Judith; TAMBY, Jean-Francois; VERRIER, Melanie; AGNETTI, Veronique; ANDERSEN, Dorthe; BADREDDINE, Emmy; BEKKOUCHE, Mhamed; BOUANCHEAU, Cecile; BRIGUI, Imane; BROCKLEHURST, Maddy; CIANCIARULO, Joseph; DEVAUL, Dawn; DOMOKOS, Szilvia; GACHE, Cecile; GOBILLOT, Caroline; GUILLOU, Severine; HEALY, Jan; HEATH, Megan; JAIWAL, Gayatri; JAVIERRE, Carine; LABEIRIE, Julien; MONIER, Myriam; MORALES, Ulises; MRABTI, Asmaa; MTHOMBENI, Bicky; OKAN, Betim; SMITH, Lucile; SHELLER, Jennifer; SOPENA, Sebastien; PELLAN, Valerie; BENBERNOU, Fadela; BENGRAIT, Nafissa; LAMOUREUX, Maud; KRALOVA, Katarina; SCEMAMA, Michel; BEJUIT, Raphael; COULANGE, Anthony; BERTHOU, Christelle; REPINCAY, Jerome; LORENZATO, Christelle; ETIENNE, Alexis; GOUET, Valerie; LOIZEAU, Virginie; NORMAND, Mickael; OURLIAC, Anne; RONDEL, Christelle; ADAMO, Antony; BELTRAN, Pascale; BARRAUD, Pauline; DUBOIS-GACHE, Helene; HALLE, Benjamin; METWALLY, Lamia; MOURGUES, Maxime; SOTTY, Marc; VINCENDET, Marion; COTRUTA, Raluca; Zhu Chengyue; FOURNIE-LLORET, Dominique; MORRELLO, Christine; PERTHUIS, Aurelie; PICAULT, Patrick; ZOBOUYAN, Isabelle |
Parte de: | LANCET DIABETES & ENDOCRINOLOGY, v.7, n.8, p.618-628, 2019 |
Resumo: | Background After acute coronary syndrome, diabetes conveys an excess risk of ischaemic cardiovascular events. A reduction in mean LDL cholesterol to 1.4-1.8 mmol/L with ezetimibe or statins reduces cardiovascular events in patients with an acute coronary syndrome and diabetes. However, the efficacy and safety of further reduction in LDL cholesterol with an inhibitor of proprotein convertase subtilisin/kexin type 9 (PCSK9) after acute coronary syndrome is unknown. We aimed to explore this issue in a prespecified analysis of the ODYSSEY OUTCOMES trial of the PCSK9 inhibitor alirocumab, assessing its effects on cardiovascular outcomes by baseline glycaemic status, while also assessing its effects on glycaemic measures including risk of new-onset diabetes. Methods ODYSSEY OUTCOMES was a randomised, double-blind, placebo-controlled trial, done at 1315 sites in 57 countries, that compared alirocumab with placebo in patients who had been admitted to hospital with an acute coronary syndrome (myocardial infarction or unstable angina) 1-12 months before randomisation and who had raised concentrations of atherogenic lipoproteins despite use of high-intensity statins. Patients were randomly assigned (1: 1) to receive alirocumab or placebo every 2 weeks; randomisation was stratified by country and was done centrally with an interactive voice-response or web-response system. Alirocumab was titrated to target LDL cholesterol concentrations of 0.65-1.30 mmol/L. In this prespecified analysis, we investigated the effect of alirocumab on cardiovascular events by glycaemic status at baseline (diabetes, prediabetes, or normoglycaemia)-defined on the basis of patient history, review of medical records, or baseline HbA(1c) or fasting serum glucose-and risk of new-onset diabetes among those without diabetes at baseline. The primary endpoint was a composite of death from coronary heart disease, non-fatal myocardial infarction, fatal or non-fatal ischaemic stroke, or unstable angina requiring hospital admission. ODYSSEY OUTCOMES is registered with ClinicalTrials. gov, number NCT01663402. Findings At study baseline, 5444 patients (28.8%) had diabetes, 8246 (43.6%) had prediabetes, and 5234 (27.7%) had normoglycaemia. There were no significant differences across glycaemic categories in median LDL cholesterol at baseline (2.20-2.28 mmol/L), after 4 months' treatment with alirocumab (0.80 mmol/L), or after 4 months' treatment with placebo (2.25-2.28 mmol/L). In the placebo group, the incidence of the primary endpoint over a median of 2.8 years was greater in patients with diabetes (16.4%) than in those with prediabetes (9.2%) or normoglycaemia (8.5%); hazard ratio (HR) for diabetes versus normoglycaemia 2.09 (95% CI 1.78-2.46, p<0.0001) and for diabetes versus prediabetes 1.90 (1.65-2.17, p<0.0001). Alirocumab resulted in similar relative reductions in the incidence of the primary endpoint in each glycaemic category, but a greater absolute reduction in the incidence of the primary endpoint in patients with diabetes (2.3%, 95% CI 0.4 to 4.2) than in those with prediabetes (1.2%, 0.0 to 2.4) or normoglycaemia (1.2%, -0.3 to 2.7; absolute risk reduction p(interaction) = 0.0019). Among patients without diabetes at baseline, 676 (10.1%) developed diabetes in the placebo group, compared with 648 (9.6%) in the alirocumab group; alirocumab did not increase the risk of new-onset diabetes (HR 1.00, 95% CI 0.89-1.11). HRs were 0.97 (95% CI 0.87-1.09) for patients with prediabetes and 1.30 (95% CI 0.93-1.81) for those with normoglycaemia (p(interaction) = 0.11). Interpretation After a recent acute coronary syndrome, alirocumab treatment targeting an LDL cholesterol concentration of 0.65-1.30 mmol/L produced about twice the absolute reduction in cardiovascular events among patients with diabetes as in those without diabetes. Alirocumab treatment did not increase the risk of new-onset diabetes. |
Aparece nas coleções: | Artigos e Materiais de Revistas Científicas - FM/MCP Departamento de Cardio-Pneumologia - FM/MCP Artigos e Materiais de Revistas Científicas - HC/InCor Instituto do Coração - HC/InCor Artigos e Materiais de Revistas Científicas - LIM/11 LIM/11 - Laboratório de Cirurgia Cardiovascular e Fisiopatologia da Circulação Artigos e Materiais de Revistas Científicas - ODS/03 ODS/03 - Saúde e bem-estar |
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