2019 · JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY

Alirocumab Reduces Total Nonfatal Cardiovascular and Fatal Events The ODYSSEY OUTCOMES Trial

Szarek, Michael, White, Harvey D., Schwartz, Gregory G., Alings, Marco, Bhatt, Deepak L., Bittner, Vera A., Diaz, Rafael, Edelberg, Jay M., Goodman, Shaun G., Hanotin, Corinne, Harrington, Robert A., Jukema, J. Wouter, Kimura, Takeshi, Kiss, Robert Gabor, Lecorps, Guillaume, Mahaffey, Kenneth W., Moryusef, Angele, Pordy, Robert, Roe, Matthew T., Tricoci, Pierluigi, Xavier, Denis, Zeiher, Andreas M., Steg, 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, Ramos Lopez, Gabriel Arturo, Alings, Marco, Halvorsen, Sigrun, Correa Flores, Roger M., 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, de Silva, H. Asita, 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, Van Diepen, Sean F. P., 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., Alves De Lima, Alberto E., Schmidberg, Jorge M., Duronto, Ernesto A., Caruso, Orlando C., Novaretto, Leonardo P., Angel Hominal, Miguel, Montana, Oscar R., Caccavo, Alberto, Gomez Vilamajo, Oscar A., 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., Ahuad Guerrero, Rodolfo A., Novoa, Federico, Patocchi, Cristian A., Zaidman, Cesar J., Giuliano, Maria E., Dran, Ricardo D., Vico, Marisa L., Carnero, Gabriela S., Guzman, Pablo N., Medrano Allende, Juan C., Garcia Brasca, Daniela F., Bustamante Labarta, Miguel H., 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, Oqueli Flores, Romulo E., 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., De Wolf, Luc, 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, de Santos, Mayler O. N., Neuenschwander, Fernando, Bodanese, Luiz C., Michalaros, Yorghos L., Eliaschewitz, Freddy G., Vidotti, Maria H., Leaes, Paulo E., Botelho, Roberto V., Kaiser, Sergio, Fernandes Manenti, Euler Roberto F., Precoma, Dalton B., Moura Jorge, Jose C., Silva, Pedro G. M. de B., Silveira, Jose A., Saporito, Wladmir, Marin Neto, Jose A., Feitosa, Gilson S., Ritt, Luiz Eduardo F., de Souza, Juliana A., Costa, Fernando, Souza, Weimar K. S. B., Reis, Helder J. L., Machado, Leandro, Aidar Ayoub, Jose Carlos, 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, De Salazar, Dora I. Molina, 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, De Leon, Edgar R. Rodriguez, 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, De Pellegrin, Annamaria, Guardigli, Gabriele, Licciardello, Giovanni, Auguadro, Carla, Cuccia, Claudio, Salvioni, Alessandro, Musumeci, Giuseppe, Calabro, Paolo, Novo, Salvatore, Faggiano, Pompilio, De Cesare, Nicoletta B., Berti, Sergio, Cavallini, Claudio, Puccioni, Enrico, Galvani, Marcello, Tespili, Maurizio, Piatti, Piermarco, Palvarini, Michela, De Luca, Giuseppe, Violini, Roberto, De Leo, Alessandro, 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, Garcia Castillo, Armando, Carrillo Calvillo, Jorge, Fajardo Campos, Pedro, Nunez Fragoso, Juan Carlos, Bayram Llamas, Edmundo Alfredo, Alcocer Gamba, Marco Antonio, Carranza Madrigal, Jaime, Gonzalez Salas, Luis Gerardo, Lopez Rosas, Enrique, Gonzalez Diaz, Belinda, Salcido Vazquez, Eduardo, Nacoud Ackar, Alfredo, Llamas Esperon, Guillermo Antonio, Martinez Sanchez, Carlos Rodolfo, Guerrero De Leon, Maria, Suarez Otero, Rodrigo, Fanghanel Salmon, Guillermo, Perez Rios, Jesus Antonio, Garza Ruiz, Jose Angel, Breedveld, Robert W., Hoogslag, Pieter A. M., Suryapranata, Harry, Oomen, Antonius, Wiersma, Jacobijne J., Van Der Wal, Ruud M. A., Van Huysduynen-Monraats, Pascalle S. Hooft, 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., Van Der Zwaan, Coenraad C., 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. 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Journal
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
Année
2019
Volume
73
Numéro
4
Pages
387-396
Mois
FEB 5
DOI
10.1016/j.jacc.2018.10.039

Abstract

BACKGROUND The ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) trial compared alirocumab with placebo, added to high-intensity or maximum-tolerated statin treatment, after acute coronary syndrome (ACS) in 18,924 patients. Alirocumab reduced the first occurrence of the primary composite endpoint and was associated with fewer all-cause deaths. OBJECTIVES This pre-specified analysis determined the extent to which alirocumab reduced total (first and subsequent) nonfatal cardiovascular events and all-cause deaths in ODYSSEY OUTCOMES. METHODS Hazard functions for total nonfatal cardiovascular events (myocardial infarction, stroke, ischemia-driven coronary revascularization, and hospitalization for unstable angina or heart failure) and death were jointly estimated, linked by a shared frailty accounting for patient risk heterogeneity and correlated within-patient nonfatal events. An association parameter also quantified the strength of the linkage between risk of nonfatal events and death. The model provides accurate relative estimates of nonfatal event risk if nonfatal events are associated with increased risk for death. RESULTS With 3,064 first and 5,425 total events, 190 fewer first and 385 fewer total nonfatal cardiovascular events or deaths were observed with alirocumab compared with placebo. Alirocumab reduced total nonfatal cardiovascular events (hazard ratio: 0.87; 95% confidence interval: 0.82 to 0.93) and death (hazard ratio: 0.83; 95% confidence interval: 0.71 to 0.97) in the presence of a strong association between nonfatal and fatal event risk. CONCLUSIONS In patients with ACS, the total number of nonfatal cardiovascular events and deaths prevented with alirocumab was twice the number of first events prevented. Consequently, total event reduction is a more comprehensive metric to capture the totality of alirocumab clinical efficacy after ACS. (c) 2019 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation.

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