Angiotensin-Converting Enzyme Inhibitor Use And Major Cardiovascular Outcomes In Type 2 Diabetes Mellitus Treated With The Dipeptidyl Peptidase 4 Inhibitor Alogliptin
William B. White,Craig A. Wilson,George L. Bakris,Richard M. Bergenstal,Christopher P. Cannon,William C. Cushman,Simon K. Heller,Cyrus R. Mehta,Steven E. Nissen,Faiez Zannad,Stuart Kupfer, Jorge Aiub, Juan Albisu, Carlos Alvarez, Alfredo Astesiano, Raul Barcudi, Mario Bendersky, Julio Bono, Betina Bustos, Luis Cartasegna, Orlando Caruso, Horacio Casabe, Remo Castro, Hugo Colombo, Carlos Cuneo, Fernando Cura, Luis De Loredo, Ricardo Dran, Horacio Fernandez, Jorge Garcia Pinna, Adrian Hrabar, Maria Klyver De Saleme, Hugo Luquez, Ignacio Mackinnon, Laura Maffei, Claudio Majul, Marcelo Mallagray, Javier Marino, Diego Martinez, Roberto Martingano, Daniel Nul, Maria Leonor Parody, Jacqueline Petrucci, Mario Pieroni, Daniel Piskorz, Aldo Prado, Hugo Ramos, Jorge Resk, Marcelo Rodriguez, Carlos Rojas, Rodolfo Sarjanovich, Alejandro Sarries, Horacio Sessa, Sandra Silveiro, Maria Ines Sosa Liprandi, Jorge Tartaglione, Hugo Tonin, Julio Vallejos, Santiago Vigo, Virginia Visco, Nestor Vita, Daniel Vogel, Oscar Vogelmann, Cesar Zaidman, Pedro Zangroniz, David Colquhoun, Steven Coverdale, Steve Flecknoe-Brown, Chris Sing Loi Hii, Philip Roberts-Thomson, Heinz Drexel, Anton Luger, Thomas Pieber, Frank Cools, Johannes Ruige, Danny Schoors, Chris Vercammen, Bart Wollaert, Fernando Alves Da Costa, Celso Amodeo, Rejane Baggenstoss, Eduardo Barbosa, Weimar Kunz Barroso De Souza, Roberto Bassan, Joao Lindolfo Borges, Roberto Botelho, Maria Christiane Valeria Braile, Helio Castello, Carolina Chrisman, Fabio Dos Santos, Jose Faria Neto, Pedro Farsky, Alessandra Fernandes Da Costa, Fadlo Fraige Filho, Benito Garbelini, Maria Fernanda Garcia, Pedro Garzon, Artur Eduardo Guimaraes, Artur Herdy, Mauro Hernandes, Sandra Hilgemberg, Miguel Hissa, Jose Antonio Jatene, Adrian Kormann, Paulo Leaes, Felipe Lima, Hugo Roberto Lisboa, Lilia Maia, Francisco Maia Da Silva, Daniela Maldonado Franco, Jose Fernando Martin, Ana Medeiros, Yorghos Michalaros, Andressa Miguel Leitao, Sergio Montenegro, Joao Moraes Junior, Marco Mota Gomes, Maria Sanali Paiva, Dalton Precoma, Alvaro Rabelo, Gilmar Reis, Helder Reis, Paulo Rossi, Wladmir Saporito, Rogerio Sarmento Leite, Ricardo Pereira Silva, Delcio Silva Junior, Luciano Sousa, Antonio Carlos Sousa, Ricardo Ueda, Fabio Vilas-Boas, Marco Wainstein, Alexandre Zago, Mashka Angelova, Emilia Apostolova, Ivona Daskalova, Alexy Delchev, Kiril Hristozov, Mariana Ilieva, Sneghina Kovacheva, Maria Lucheva, Margarita Temelkova, Antoaneta Toneva, Vyara Videva, Emilina Vuchkova, Asaad Bakbak, Andre Carpentier, Yun Kai Chan, Asim Cheema, Guy Chouinard, James Conway, Jean-Pierre Dery, Anthony Dowell, Andre Frechette, Marek Jakubowski, Allan Kelly, Patrick Ma, Tun Zan Maung, Shamir Mehta, David Parker, Yves Pesant, Petr Polasek, Thomas Ransom, Gurcharan Syan, Saul Vizel, Francisco Albornoz, Pablo Castro Galvez, Jorge Leonardo Cobos, Carlos Conejeros, Mauricio D'Acuna Apablaza, Graciela Fajardo, Guillermo Illanes Brochet, Marcos Opazo Lazcano, Christian Pincetti, Sergio Potthoff, Carlos Raffo, Victor Saavedra, Maria Schnettler, Pablo Sepulveda, Benjamin Stockins, Margarita Vejar, Jose Luis Accini, Carlos Hernan Cotes Aroca, Ricardo Leon Fernandez Ruiz, Luis Alejandro Orozco Linares, Boris Eduardo Vesga Angarita, Izet Aganovic, Jugoslav Bagatin, Silvija Canecki-Varzic, Dubravka Jurisic Erzen, Aleksandar Knezevic, Andreja Maric, Goran Milicevic, Zeljko Popovic, Josip Rubes, Sonja Slosic Weiss, Irma Dresslerova, Jana Havelkova, Dusan Kucera, Josef Machacek, Jiri Pumprla, Ole May, Hans Perrild, Magdy Abdel Aziz, Mahmoud El Badry, Mahmoud Hasanein, Juhani Airaksinen, Mika Laine, Kai Nyman, Saila Vikman, Jacques Bonnet, Meyer Elbaz, Patrick Henry, Francois Paillard, Catherine Petit, Anne-Isabelle Tropeano, Thomas Behnke, Stefan Bornstein, Klaus Busch, Henning Ebelt, Marcus Faghih, Hermann Fischer, Hubertus Heuer, Ralf Paschke, Tudor-Constantin Porner, Gerard Tangerding, Hans-Friedrich Voehringer, Karen Adamson, Kevin Beatt, Srikanth Bellary, John Chapman, Alastair Cooke, Miles Fisher, Luigi Gnudi, Hugh Jones, Sudhesh Kumar, Dinesh Nagi, Keith Oldroyd, Tristan Richardson, Douglas Robertson, Anthony Robinson, Ponnusamy Saravanan, Adie Viljoen, John Wilding, Peter Wilkinson, Yuk-Ki Wong, Christos Zoupas, Juan Arango, Jose Castellanos, Carlos Ceren Flores, Vinicio Corona, Arnoldo Granados-Fuentes, Franklin Haase, Pablo Montenegro, Julio Humberto Palencia Prado, Renato Villalobos, Francis Chow, Shu Kin Li, June Li, Ping Yen Bryan Yan, Vincent Yeung, Tatjana Abel, Amalia Benedek, Eniko Dezso, Mihaly Dudas, Istvan Edes, Gabor Fulop, Aranka Kovacs, Geza Lupkovics, Bela Merkely, Andras Nagy, Tamas Oroszlan, Attila Palinkas, Andras Papp, Jozsef Patkay, Eva Simon, Eva Sitkei, Adam Tabak, Janos Tomcsanyi, Jabir Abdullakutty, Atul Abhyankar, Umesh Akalkotkar, Thomas Alexander, Jaspal Arneja, Naved Aslam, Pothineni Ramesh Babu, Byrapaneni Ramesh Babu, Darshan Banker, Ganapati Bantwal, P. R. Bhimashankar, Rajneesh Kumar Calton, Manoj Chopda, Ajay Dande, Sameer Dani, Neeta Deshpande, Niteen Deshpande, Dinesh Dhanwal, Aniruddha Dharmadhikari, Milind Gadkari, Nitish Garg, Nitin Ghaisas, N. K. Goyal, Jugal Bihari Gupta, Anil Jawahirani, Stigmon Joseph, Ravi Kumar, Mukund Kumble, A. Mathavan, Atul Mathur, Padnihare Purayil Mohanan, Abhilash Nair, Tiny Nair, Deepak Namjoshi, Robin Pinto, Guru Prakash, R. Purushotham, Srinivas Raju, Padmakumar Ramachandran, S. S. Ramesh, Bhaskara Rao, Amancherla Ravikishore, G. Rajashekar Reddy, Sanjeeb Roy, Nehal Sadhu, B. K. S. Sastry, Parvinder Singh, Arun Srinivas, Hemant Thacker, Sunil Thanvi, Joy Thomas, Faiad Adawi, Amir Bashkin, Josef Cohen, Ilana Harman-Boehm, Yonathan Hasin, Tony Hayek, Zaza Iakobishvili, Amos Katz, Oscar Kracoff, Oscar Minuchin, Mady Moriel, Morris Mosseri, Muhamad Omary, Julio Wainstein, Avraham Weiss, David Zeltser, Paolo Calabro, Giuseppe Derosa, Stefano Genovese, Salvatore Novo, Carlo Olivieri, Piermarco Piatti, Roberto Violini, Massimo Volpe, Masayoshi Ajioka, Tetsuya Amano, Osamu Arasaki, Hiroyuki Daida, Kazuteru Fujimoto, Hiroyuki Fujinaga, Shinichi Higashiue, Atsushi Hirohata, Shinobu Hosokawa, Hiroyuki Ikefuji, Masayuki Inagaki, Harukazu Iseki, Masashi Iwabuchi, Toshiya Iwasaki, Mikio Kakishita, Yousuke Katsuda, Kimiko Kawada, Kenji Kawajiri, Katsunori Kawamitsu, Katsuyuki Kobayashi, Fumihiko Komada, Yasuo Komura, Masaharu Machida, Koji Maemura, Taku Matsubara, Sunao Matsubayashi, Tomoaki Matsumoto, Naoki Matsumoto, Tsutomu Mima, Nobuhide Miyamoto, Yukihiko Momiyama, Takafumi Morimoto, Marohito Murakami, Eitaro Nakashima, Yawara Niijima, Toshiyuki Noda, Koichi Node, Akira Nozaki, Tatsuya Nunohiro, Tomohiro Ogawa, Yasuhiro Ono, Takahiro Saeki, Shinichiro Sakota, Satoru Sakuragi, Toyoshi Sasaki, Yasuhiro Sato, Atsushi Sueyoshi, Masahiro Suzuki, Gen Takagi, Jun Tanabe, Seiichi Tanaka, Imun Tei, Masato Yamamoto, Kaoru Yanagihara, Taek Jong Hong, Hui-Kyung Jeon, Duk-Hyun Kang, Cheol Ho Kim, Dong-Soo Kim, Hyun-Sook Kim, June Hong Kim, Soon Kil Kim, Woo-Shik Kim, Young-Kwon Kim, Sangrok Lee, Kwan-Woo Lee, Hun-Sik Park, Wook Bum Pyun, Seung-Woon Rha, Junghan Yoon, Kun-Ho Yoon, Abdullah Bennakhi, Kristine Geldnere, Jelena Sokolova, Dace Teterovska, Violeta Dautaraite, Vaida Kakariekiene, Roma Kavaliauskiene, Alina Kucinskiene, Jurate Lasiene, Narseta Mickuviene, Algirdas Palinauskas, Audrone Urboniene, Birute Zilaitiene, Hasmannizar Abdul Manap, Imran Zainal Abidin, Siti Harnida Md Isa, Amir Md. Khir, Kok Huan Ng, Florence Tan, Zurkurnai Yusof, Khalid Yusoff, Robaayah Zambahari, Javier Aguila-Marin, Manuel Aguilera Real, Ricardo Alvarado-Ruiz, Humberto Alvarez Lopez, Jose Arenas Leon, Edmundo Alfredo Bayram Llamas, Cesar Calvo Vargas, Jorge Carrillo Calvillo, Manuel De Los Rios Ibarra, Carlos Alberto Dominguez-Reyes, Manuel Duarte, Eduardo Elizondo, Pedro Fajardo Campos, Guillermo Fanghanel-Salmon, Sergio Figueroa Sauceda, Jose Gallegos Martinez, Elias Garcia-Cantu, Jose Angel Garza Ruiz, Jose Gerardo Gonzalez Gonzalez, Manuel Guerrero Garza, Carlos Hernandez Herrera, Jesus Hernandez Munuzuri, Hugo Hernandez-Garcia, Silvia Jimenez Ramos, Hugo Laviada Molina, David Lopez Villezca, Efrain Montano-Gonzalez, Luis Nevarez Ruiz, Gabriel Ramos Lopez, Raul Reyes Araiza, Abel Salazar-Gaytan, Eduardo Salcido Vazquez, Hector Sanchez Mijangos, Lucas Solis Morales, Jocelyne Benatar, Paul Dixon, Kingsley Nirmalaraj, Ian Rosen, Russell Scott, Simon Young, Ofelia Araoz Tarco, Luis Barreda Caceres, Carmen Benites Lopez, Luis Camacho Cosavalente, Edith Chavez Huapalla, Augusto Chois Malaga, Alex Copaja Flores, Julio Farfan Aspilcueta, Wilson Gallardo Rojas, Alex Gallegos Cazorla, David Galvez Caballero, Julio Garcia Matheus, Elizabeth Garrido Carrasco, Jorge Gomez Sanchez, Jose Hernandez Zuniga, Libia Lu Galarreta, Alejandro Luna, Helard Manrique Hurtado, Boris Orihuela Pastor, Rosa Maria Pando Alvarez, Javier Sanchez Povis, Pedro Torres Eguiluz, Angelica Valdivia Portugal, Rolando Vargas Gonzales, Luis Zapata Rincon, Grace Aquitania, Judy Theresa Fortinez, Angelita Go, Maria Honolina Gomez, Ramoncito Habaluyas, Gabriel Jasul, Marie Magno, Carlo John Manalo, Roberto Mirasol, Ellen Morales-Palomares, David Raymund Salvador, Rosa Allyn Sy, Louie Tirador, Christy Yao, Malgorzata Arciszewska, Radoslaw Bartkowiak, Eugenia Czajkowska-Kaczmarek, Robert Gil, Jacek Gniot, Krzysztof Janik, Marianna Janion, Krystyna Jaworska, Robert Jozwa, Kalina Kawecka-Jaszcz, Teresa Kawka-Urbanek, Marek Kondys, Janusz Korecki, Romuald Korzeniak, Alicja Kowalisko, Maria Krzeminska-Pakula, Jolanta Kwiecien, Jadwiga Nessler, Piotr Odrowaz-Pieniazek, Marek Piepiorka, Marek Rajzer, Ewa Skokowska, Janusz Spyra, Michal Sroka, Teresa Stasinska, Ireneusz Szymczyk, Iwona Trznadel-Morawska, Andrzej Wysokinski, Pedro Mateus, Pedro Matos, Jorge Mimoso, Pedro Monteiro, Baruch Caballero, Raul Garcia-Rinaldi, Elena Gonzalez, Ramon Ortiz-Carrasquillo, Amaury Roman, Yolanda Sierra, Nestor Unger, Jose Vazquez-Tanus, Tom Alexandru, Mihaela Busegeanu, Doina Constanta Cozman, Simona Fica, Bogdan Minescu, Magdalena Morosanu, Gabriela Doina Negrisanu, Ella Pintilei, Lavinia Pop, Iosif Szilagyi, Iulia Teodorescu, Mirela Tomescu, Olga Barbarash, Galina Chumakova, Svetlana Churina, Sergey Dogadin, Irina Dvoryashina, Valeria Esip, Maria Glezer, Ivan Gordeev, Alexander Gordienko, Nikolay Gratsiansky, Elena Grineva, Niaz Khasanov, Victor Kostenko, Tatiana Meleshkevich, Vadim Mikhin, Tatyana Morugova, Igor Motylev, Konstantin Nikolaev, Asya Ponomareva, Mikhail Repin, Olga Reshetko, Sergey Shustov, Elena Shutemova, Yury Shvarts, Vladimir Simanenkov, Konstantin Sobolev, Irina Sukmanova, Alexander Timofeev, Larisa Tsyba, Galina Varvarina, Arkadiy Vertkin, Alexander Vishnevsky, Dmitry Volkov, Sergey Vorobiev, Natalya Vorokhobina, Davyd Yakhontov, Elena Zonova, Konstantin Zrazhevskiy, Svetozar Damjanovic, Dragan Djordjevic, Milan Pavlovic, Jovan Perunicic, Arsen Ristic, Sinisa Stojkovic, Nebojsa Tasic, Nora Bolvanska, Ingrid Buganova, Katarina Dulkova, Andrej Dzupina, Peter Fulop, Vladimir Gergel, Martin Kokles, Karol Micko, Peter Svoren, Miroslav Urban, Silvia Vadinova, Anna Vargova, Leslie Burgess, Kathleen Coetzee, Jacques Du Toit, Mashra Gani, Pankaj Joshi, Puvanesveri Naiker, Hendrik Nortje, Mahomed Sarvan, Mary Seeber, Mirna Siebert, Louis Van Zyl, Holger Wellmann, Carlos Calvo, Jesus De La Hera, Luis De Teresa, Antonio Melero-Pita, Jordi Mesa, Juan Parra Barona, Pedro Serrano, Alfonso Soto, Santiago Tofe, Bjorn Hornestam, Anders Kempe, Ulf Rosenqvist, Erik Rydberg, Bengt-Olov Tengmark, Ingemar Torstensson, Chwen-Tzuei Chang, Te-Lin Hsia, I-Chang Hsieh, Wen-Ter Lai, Chiung-Jen Wu, Pisit Hutayanon, Natapong Kosachunhanun, Mongkol Marapracertsak, Chumpol Piamsomboon, Samroeng Seekaew, Suphot Srimahachota, Pradub Sukhum, Swangjit Suraamornkul, Puntip Tantiwong, Chaiyasith Wongvipaporn, Kateryna Amosova, Olga Barna, Andriy Bazylevych, Vadym Berenfus, Alexander Dyadyk, Ivan Fushtey, Olga Gyrina, Mykola Iabluchanskyi, Oleksandr Karpenko, Igor Kaydashev, Oleksii Korzh, Roman Kulynych, Olexandr Legkonogov, Boris Mankovsky, Yuriy Mostovoy, Oleksandr Parkhomenko, Galyna Popik, Leonid Rudenko, Iurii Rudyk, Sergii Shevchuk, Yuriy Sirenko, Yevgen Suprun, Nadiya Tryshchuk, Vira Tseluyko, Igor Vakaliuk, Wael Al Mahmeed, Roger Acheatel, Anwar Ahmad, Saleem Akbar, Faiq Akhter, Abdulhay Albirini, Arnold Alexander, Bassam Al-Joundi, Tammam Al-Joundi, Gregory Allen, Joseph Aloi, Odilon Alvarado, Opada Alzohaili, Corey Anderson, Anwar Arastu, Charles Arena, Georges Argoud, Mehrdad Ariani, Chander Arora, Vivek Awasty, Barbara Barker, Otis Barnum, Anthony J. Bartkowiak, Joshua Barzilay, Phillip Behrens, Mario Belledonne, Bradford Bergman,William Bilnoski, John Bisognano, Stephen Bissette, Edwin Blumberg, Nagadeh Bonabi, Arden Bradley, Cristian Breton, Martin Britos, Vasti Broadstone, Matthew Budoff, Mark Burge, Samuel Butman, Mary Carroll, Krishnan Challappa, Vinaya Chepuri, Richard Cherlin, Deanna Cheung, Peter Coats, John Collins, Humberto Cruz, Nizar Daboul, Greg Damberg, William David, Julius Dean, Eric Dedeke, Wasim Deeb, Joseph Dehaven, Adrian Dobs, Timothy Donelan, Johnny Dy, Gary Dykstra, Howard Eisen, Neil Farris, Peter Fattal, Norman Fishman, Malcom Foster, Sonja Fredrickson, Nashwa Gabra, John Gabriel, Lionel Gatien, Stephen Giddings, Burton Ginsberg, Sanford Gips, Mariela Glandt, Aaron Goldfein, Murray Gordon, Randy Gould, Ronald Graf, Bruce Graham, Mark Graves, Paul Grena, Richard Hahn, Dale Hamilton, Glenn Hamroff, Forrest Hanke, Ihsan Haque, James Harper, Anthony Harris, Sharon Harris, Bruce Henson, David Hermanns, William Herndon, Vernon Hershberger, Daniel Hyman, Steven Isserman, Bruce Iteld, Moshir Jacob, Naseem Jaffrani, Aamir Jamal, David Johnson, Glover Johnson, Edo Kaluski, Robert Keller, Dean Kereiakes, Muhammad Khan, Salman Khan, Misal Khan, Michael Klein, Thomas Knutson, Elie Korban, Marc Kozinn, Philip Kraft, James Kroeze, Eugene Kukuy, Ellis Lader, Aristotelis Laliotis, Charles Lambert, Charles Landau, Kashif Latif, Kwan Lee, F. Lester, David Levenson, Dennis Levinson, Derek Lewis, Marc Litt, Ronald Littlefield, Eric Lo, Charles Lovell, Sharan Mahal, Satyaprakash Makam, Mustafa Mandviwala, Isam Marar, Bassem Masri, Steven Mattson, Maureen Mays, Frank Mcgrew, Mark Meengs, Frank Mikell, Michael Miller, Francisco Miranda, David Moll, Pramod Multani, Karan Munuswamy, Mani Nallasivan, Lee Nayles, Stephen Ong, Theodore Pacheco, Henry Paez, Shailendra Patel, Roland Phillips, Brien Pierpont, Jeereddi Prasad, Edward Quinlan, Jun Quion, Mansoor Qureshi, Aref Rahman, Marina Raikhel, Kodangudi Ramanathan, Preet Randhawa, Ram Ravi, Rajneesh Reddy, Marc Rendell, Kyle Rickner, Kenneth Rictor, Jose Rivas, Paul Rosenblit, Julio Rosenstock, Steven Ross, Abraham Salacata, Mehrdrad Saririan, Susan Schima, Aron Schlau, John Schmedtje, Cranford Scott, David Scott, Antonio Serru-Paez, Rakesh Shah, Anil Shah, Emanuel Shaoulian, Mansur Shomali, Jay Shubrook, Kevin Silver, Sanjay Singh, John Speer, Jewel Stevens, Stanley Stringam, Andrew Taussig, Angela Taylor, Howard Tee, Gilbert Teixeira, Absalom Tilley, Edward Toggart, Marcel Twahirwa, Dennis Unks, Babak Vakili, Kishor Vora, Xiangbing Wang, Alberta Warner, Franklin Wefald, Bradley Weinberg, Debra Weinstein, Lindsey White, Patricia Wu, Tsunehiro Yasuda, Shahram Yazdani, Cornelius Yetman, Stuart Zarich, James Zebrack
HYPERTENSION（2016）
引用 27|浏览9
摘要
Activation of the sympathetic nervous system when there is dipeptidyl peptidase 4 inhibition in the presence of highdose angiotensin-converting enzyme (ACE) inhibition has led to concerns of potential increases in cardiovascular events when the 2 classes of drugs are coadministered. We evaluated cardiovascular outcomes from the EXAMINE (Examination of Cardiovascular Outcomes With Alogliptin versus Standard of Care) trial according to ACE inhibitor use. Patients with type 2 diabetes mellitus and a recent acute coronary syndrome were randomly assigned to receive the dipeptidyl peptidase 4 inhibitor alogliptin or placebo added to existing antihyperglycemic and cardiovascular prophylactic therapies. Risks of adjudicated cardiovascular death, nonfatal myocardial infarction and stroke, and hospitalized heart failure were analyzed using a Cox proportional hazards model in patients according to ACE inhibitor use and dose. There were 3323 (62%) EXAMINE patients treated with an ACE inhibitor (1681 on alogliptin and 1642 on placebo). The composite rates of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke were comparable for alogliptin and placebo with ACE inhibitor (11.4% versus 11.8%; hazard ratio, 0.97; 95% confidence interval, 0.79-1.19; P=0.76) and without ACE inhibitor use (11.2% versus 11.9%; hazard ratio, 0.94; 95% confidence interval, 0.73-1.21; P=0.62). Composite rates for cardiovascular death and heart failure in patients on ACE inhibitor occurred in 6.8% of patients on alogliptin versus 7.2% on placebo (hazard ratio, 0.93; 95% confidence interval, 0.72-1.2; P=0.57). There were no differences for these end points nor for blood pressure or heart rate in patients on higher doses of ACE inhibitor. Cardiovascular outcomes were similar for alogliptin and placebo in patients with type 2 diabetes mellitus and coronary disease treated with ACE inhibitors.
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关键词
alogliptin,angiotensin II,angiotensin-converting enzyme inhibitors,dipeptidyl dipeptidase 4 inhibitors,heart rate,type 2 diabetes mellitus
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