Evolocumab to Reduce First Major Cardiovascular Events in Patients Without Known Significant Atherosclerosis and With Diabetes

作者：Nicholas A. Marston, Erin A. Bohula, Ajay Bhatia, Gaetano M. De Ferrari, LA Leiter, Jose C. Nicolau, Jeong-Gun Park, S. A. Murphy, Emileigh Walsh, L. Liu, Subodh Verma, Naveed Sattar, Stephen J. Nicholls, J. Lopez-Sendon, Ioanna Gouni-Berthold, Lale Tokgozoglu, Ron Blankstein, Marcoli Cyrille, Gabriel Paiva da Silva Lima, Robert P. Giugliano, Marc S. Sabatine, VESALIUS-CV Investigators, Alberto Lorenzatti, Marcos R. Litvak Bruno, Ignacio Mackinnon, Emilio Alaguibe, Gustavo Giunta, Oscar Romano Montana, Daniel Vogel, JORGELINA SALA, Diego Besada, Angela Romero Zarante, Marisa L. Vico, Tomas E. Smith Casabella, Patricia del C. Gonzalez Colaso, Eleonora Montenegro, Cesar Javier Zaidman, Maria C. de Salvo, Eduardo R. Perna, Claudio Majul, Ruben O Garcia Duran, Miguel Hominal, Sonia Hermida, Carolina Chacon, Andrea P. Serrano, Juan P. Albisu Di Gennaro, Walter R. Stoermann, María Mansilla, Martín Koretzky, Leonardo Novaretto, Lilia Schiavi, Andres D. Orlandini, Fernando Botto, Elizabeth Gelersztein, Eduardo Blumberg, Stephen J. Nicholls, John Amerena, Walter P. Abhayaratna, Philip Roberts-Thomson, Matthew Worthley, C. Judkins, Fiona Bisshop, Alistair Begg, David Colquhoun, Karam Kostner, Ktut Arya, David Cross, A. Conradie, Jamie Morton, Peter Purnell, Andrew Hamilton, William Van Gaal, Ali Safaa, D. Eccleston, Christoph Ebenbichler, Peter Fasching, Ursula Hanusch, Bernhard Ludvik, Lukas Holzinger, Christoph H. Saely, Konstantin A. Krychtiuk, A. Kautzky-Willer, Thomas M. Stulnig, Peter Sinnaeve, Stéphane Carlier, Marc De Meulemeester, Bart Wollaert, Andre Peeters, Benjamin Scott, Philippe Vanduynhoven, Jan Verwerft, Tom Sarens, Luis A. Tavares Russo, Celia R. Echeverria Sampaio, Roberto R. Giraldez, Pedro Pimentel Filho, Joao L. Cunha Borges, Miguel Nasser Hissa, Jose A. Ribas Fortes, Rodrigo Cerci, Lilia Nigro Maia, Adrian P. Kormann, Flavia Arantes, Gilmar Reis, Jose F. Saraiva, Dalton Bertolim Precoma, Paulo R. Ferreira Rossi, Flavio E Giorgeto, Adamastor Humberto Pereira, Luiz C. Bodanese, Maria H Vidotti, Raphael A. Barreto da Silva, Krassimir Cvetkov, Georgi V Todorov, Valeri Gelev, Ivaylo Vasilev, Haralambi O Benov, Assen Goudev, Arman Postadzhiyan, Atanas Koundurdjiev, Krastyu Penchev, Vladimir Zhelev, Mariya Tokmakova, Maria Milanova, Snezhanka Tisheva- Gospodinova, Valentina M Mincheva, M. Tzekova, Bojidar I Dimov, Krasimira Hristova-Tselova, Elena Dotcheva, Kostadin Kichukov, Robert Schlosser, David Mazer, Christian Constance, Harpreet S. Bajaj, Alexis Baass, Jason M Burstein, Sorin Beca, Sam Henein, George Tsoukas, Jean Bergeron, Daniel Gaudet, Michael Hartleib, Michael Heffernan, James Cha, Sean D. Peterson, Chetna Tailor, Hani Alasaad, Iqbal Bata, Gerald Vallieres, Ronald Bourgeois, Dennis OKeefe, Buki Ajala, Vincent Woo, Derek Yung, Hasnain Khandwala, Dante Manyari, Milan Gupta, Eva Lonn, Jacob Udell, Yaariv Khaykin, Petr Fráňa, Stanislav Zemek, Libor Sknouril, Alexandr Schee, Ladislav Pazdera, Pavel Koleckar, E. Zidkova, Juraj Bujdák, J Kvasnička, Vladimir Blaha, Robin Urbánek, Petr Reichert, Ivo Podpera, Petr Ďulíček, Martina Machkova, Nadezda Fiserova, Sylva Brtnikova, Zbyněk Pozdíšek, Michal Cepelak, Vladimir Cech, Miroslav Homza, Janka Škrobáková, Lubomír Elbl, Petr Kala, Lea Raclavska, Jiří Veselý, K Sochor, Radim Kryza, Dagmar Bartášková, Jiri Krupicka, Jiří Matuška, Jakub Hron, Marian Pirchala, Ladislav Busak, Dusan Kucera, Lukáš Zlatohlávek, Marek Houra, Vít Řezníček, Jaroslav Brotánek, Rostislav Polášek, Ilona Pařenicová, Lumír Francek, Milan Sepši, Jan Vaclavik, Pavel Kukla, Ladislav Kuchař, Igor Karen, Roman Miklík, Zbynek Kosek, Nikolaj T. Krarup, Henrik Kjaerulf Jensen, Peter Søgaard, Tem Bendix Salkvist Jorgensen, Kristian Korsgaard Thomsen, Peter Rossing, Morten Bôttcher, Nikolaj Eldrup, Elgina Kamil Thomsen, Annette Hoi Justesen, Soren R. Nielsen, Jorn M. Jepsen, Bernt Husoy, Ivo Valter, Arvo Rosenthal, Liina Viitas, Marika Paumets, Sakari Nieminen, Joni Suomi, Anna-Mari Koski, Johanna Kuusisto, Jukka Putaala, Kai Nyman, Kari Kervinen, Tuomas T. Rissanen, Janne Hukkanen, Jyrki Taurio, Timo Strandberg, Gilles Montalescot, Gilles Lemesle, Franck Boccara, Gregory Ducrocq, Marie‐Antoinette Sevestre, Bruno Farah, Thierry Fourme, François Paillard, E. Messas, Gilles Barone Rochette, Alexandre Canville, Meyer Elbaz, Pierre Poustis, Guillaume Cayla, Jean-Louis Georges, Fitsum Guebre Egziabher, Frederic Chague, Victor Buzura, Sybil Charriere, Patrick Khanoyan, Grégoire Rangé, Emile Ferrari, Bertrand Cariou, Francois Roubille, Farzin Beygui, Sébastien Caudmont, Ingo Weigmann, Isabelle Schenkenberger, Manuela Licka, Maritta Marks, Katrin Borucki, Andreas Rieth, Karl-Friedrich Appel, Ursula Kassner, Ulrich Laufs, Andreas Wilke, Christoph Axthelm, Frank Schäper, Martin Bergmann, Ksenija Stach-Jablonski, Joerg Simon, Marcus Fischer, Stefan Leggewie, Jens Taggeselle, Sebastian Cremer, Katrin Gebauer, Wolfgang Koenig, Gerd Kahrmann, Peter Bosiljanoff, Jens Placke, Marc Kollum, Bernhard Winkelmann, Konstantinos Tsioufis, Sotirios Patsilinakos, Georgios Liamis, Κωνσταντίνος Τζιόμαλος, Ioannis H Styliadis, George Ntaios, Elias Tsougos, Athanasios Protogerou, Kimon Stamatelopoulos, George Giannakoulas, Katerina Κ. Naka, Apostolos Karavidas, Niki Katsiki, Anastasios Milkas, Evgenia Mavrokefalou, Theodosios D. Filippatos, Robert Kiss, Bela Merkely, Mariann Harangi, Kalman Toth, Imre Ungi, János Tomcsányi, Zoltan Csanadi, Daniel Aradi, László Márk, Zsolt Zimmermann, Andras Papp, Géza Lupkovics, Anikó Papp, Béla Benczúr, Andrea Hornyik, Ferenc Lakatos, János Mucsi, Laszlo Nagy, I Szakál, A Mohácsi, Istvan Reiber, Jozsef Lippai, Laszlo Konyves, Csaba Hajdu, Sándor Hamar, Balazs Sarman, Attila Szilagyi, Peter Danos, Gergely G. Nagy, Tamas Barany, István Berhés, Andras C. Nagy, Piera A. Merlini, Giovanni Licciardello, Maria P.A. Baldassarre, Sergio Berti, Enrico Rinaldi, Giuliano Tocci, Salvatore De Rosa, Andrea Palermo, Nazzareno Galiè, Roberto Trevisan, Gaetano M. De Ferrari, Daniela Trabattoni, Inga Morozova, Dace Teterovska, Andrejs Erglis, Irina Veze, Inga Jasinkevica, Jolita Badariene, Lina Vencevičienė, Rimvydas Slapikas, Gediminas Urbonas, Valdas Dobilas, Danute Strazdiene, Nora Kupstytė-Krištaponė, Roma Kavaliauskiene, Enrique Villegas, Fernando Aguilera Almazán, Vicente E. Ruiz Ruiz, Marco A. Alcocer Gamba, Raymundo García Reza, Manuel De los Rios Ibarra, Ismail Aksoy, Floris Kauer, Ruud van de Wal, Anthonius Oude Ophuis, Fransisco Prins, Walter Hermans, F. Janse, Stefan Koudstaal, Mireille E. Emans, Pieter Hoogslag, G. L. Bartels, Thierry X. Wildbergh, Matthijs F.L. Meijs, Eelko Ronner, Iris C D Westendorp, Lennaert Kleijn, Pieter A. Dijkmans, Lambertus Pos, Saman Rasoul, Jeroen Schaap, M. Asselman, Margriet Feenema-Aardema, Reginald Groutars, Pieter M. H. Nierop, H. Swart, Erik Badings, Marc van Zee, Wouter Remkes, Johannes Herrman, Paul van Bergen, Erik Stroes, Simone C.C. Hartong, Adriaan Kooy, Johannes C. Post, Marcel van de Ree, Willem A. Bax, Frank Visseren, Houshang Monajemi, Saloua el Messaoudi, Ravee Rambharose, Thomas Van Bemmel, Catharina Daemen-Gubbels, Mazin Alhakim, Bernard Rensing, Rien Dekkers, Ahmet Adiyaman, Valeria Paradies, Remy H.H. Bemelmans, Boudewijn A Hoek, Ralph Verkleij, Zbigniew Bednarkiewicz, Janusz Spyra, Michal R. Tomaszewski, Maciej Zabowka, Wojciech Telec, Zbigniew Pijanowski, Mariusz Kafara, Marek Piepiorka, Jerzy Kopaczewski, Bogusław Grzegorzewski, Grzegorz Kania, Lukasz Wojnowski, Andrzej Budaj, Iwona Wozniak, Jacek Kieltucki, Wojciech Czochra, Lidia Pawłowicz, Adrian Wlodarczak, Elzbieta Dulak, Pawel Staneta, Janusz Bednarski, Benita Busz-Papiez, Beata Wozakowska-Kaplon, Piotr Rozpondek, Marlena Broncel, Tomasz Czerski, Michal Zabojszcz, Krzysztof Cieślik, Robert Glowka, Krzysztof Saminski, Marcin Skorski, Dariusz Surman, Joanna Niegowska, Piotr Napora, Piotr Karaś, Ewa Mirek-Bryniarska, Łukasz Artyszuk, Monika Tomaszewska-Kiecana, Joanna Biegajlo, Maciej Banach, Grzegorz Skonieczny, Magdalena Loster, Krzysztof Chlebus, Ewa Jazwinska-Tarnawska, Aleksander Żurakowski, Grzegorz Drelich, Dariusz Dudek, Artur Klecha, Adam Deres, Magda Dabrowska, Jerzy Cygler, Carlos Aguiar, Pedro Matos, Helder Pereira, Pedro Monteiro, Cristina Gavina, Pedro Azevedo, Manuela Vieira, Rogerio Ferreira, Olga M. Azevedo, Gabriela Stanciulescu, Constantin Militaru, Dragoş Vinereanu, Cristian Podoleanu, Marilena Spiridon, Dana Cosma, Ella Pintilei, Carmen Crisan, Laurentia D. Andrei, O.V. Averkov, Elena Radchenko, Yulia Argunova, Svetlana A. Berns, Alexander Bykov, Mikhail Voevoda, Ivan Gordeev, Dmitry Dronov, N. G. Veselovskaya, Dmitry Duplyakov, Marat V. Ezhov, Konstantin Zrazhevskiy, Mikhail Zykov, Zhanna Kobalava, Natalya Koziolova, E. D. Kosmacheva, Viktor Kostenko, Elena Kulibaba, Natalya Lozhkina, Yury V. LUKYANOV, Valeriy Makukhin, Aleksey Meshkov, Viktor A. Milyagin, Vladimir Nosov, Irina Osipova, Elena F Pavlysh, Leonid Pimenov, Vyacheslav Ryabov, Irina Semenova, O. G. Smolenskaya, Oleg Solovev, Maxim Sorokin, M. Statsenko, Tatiana Treshkur, Sergey Shalaev, Evgeny Petrik, Yury Shvarts, Valerii Popov, Elena Shutemova, Victor Mordovin, Evgeny Morozov, Ruslan Sardinov, Alexander Sherenkov, Tatiana Sveklina, Daniel Pella, Peter Fulop, Lubomir Antalik, Jozef Semetko, Ivan Majercák, Jan Nociar, Rudolf Smik, Andrej Dzupina, Daniela Vinanska, Michal Banik, Alexander Klabník, Roman Oriesek, Ivana Šoóšová, R Uhliar, Jana Lukacova, Dalibor Sosovec, J. Lacka, Dasa Skripova, L Urgeová, Kyung W. Park, Young W. Jang, Tae-Hyun Yang, Byung J. Kim, Chang-Wook Nam, Soon J. Hong, Jong‐Sook Park, Bum K. Hong, Doo S. Sim, Weon Kim, Yun-Seok Choi, Cheol W. Lee, Byeong-Keuk Kim, Myeong-Chan Cho, Joo-Yong Hahn, Sunggyun Ahn, So-Yeon Choi, In-Ho Chae, Carmen Suarez Fernandez, Daiana Ibarretxe Gerediaga, Estíbaliz Jarauta Simón, J. López Miranda, Agustín Blanco Echevarría, Francisco J. Tinahones Madueño, Nuria Alonso Pedrol, Carlos Brotons Cuixart, Juan F. Merino Torres, Juan F. Arenillas Lara, Miguel A. Vazquez Ronda, Emilio Ortega Martinez de Victoria, Rafael J. Hidalgo Urbano, Andrés Íñiguez Romo, Juanatey, Miguel Civera Andrés, Violeta Rodríguez Rodríguez, Regina Dalmau González-Gallarza, Jesus Peteiro Vazquez, Joao L. Modesto dos Santos, Jose A. Martin Armas, Pablo González‐Bustos, Domingo A. Pascual Figal, Thomas Mooe, Carl-Johan Lindholm, Asa Drakesby, Stefan Soderberg, Jacob Odenstedt, Ake Olsson, Magnus Peterson, Pekka Koskinen, Staffan Salmonsson, Rudolfs Sakne, Par Bjorklund, Tsung-Hsien Lin, Chin-Chou Huang, I‐Te Lee, Ji-Hung Wang, Hung‐I Yeh, Yi‐Chih Wang, Yi-Heng Li, I-Chang Hsieh, Chiung-Jen Wu, Chien‐Ning Huang, Vira Tseluyko, Roman Stets, Mykola Stanislavchuk, Leonid Rudenko, Mykola Rishko, Anna Popova, Oleksandr Prokhorov, Oleksandr Parkhomenko, Iuliia Melashchenko, L. Mishchenko, Yurii Lymar, Oleksii Korzh, Oleksandr Karpenko, Igor Vakaliuk, Liudmyla Alieksieieva, Olena Mitchenko, Damien Mcnally, Ryan D Costa, Terry McCormack, Adrian Beltran-Martinez, Derek Connolly, Deepa Narayanan, D Felmeden, Stephen Bain, Mary Ellen Lynch, Neil Paul, Richard Burkimsher, John Webster, Patrick Donnelly, Ponnusamy Saravanan, Louise Shaw, Basil Issa, Rashed Hossain, Ronak Rajani, Alex Bickerton, Abdul Negahban, Patrick Moore, Susan Fairhead, Amardeep Heer, Sam Davies, Peter Wilson, Alan Jackson, Shanmugapriya Ganeshkumar, Gordon W. Irvine, Anton Poterajlo, Beata Krawczyk, Paul Walukiewicz, Joshua Asubiaro, Motunrayo Adesanya, Iulia Adelina Dinu, Devaki Nair, Shamaila Aslam, Michael Lillestol, Samir Abdelshaheed, Nicolas W. Shammas, Tehreen Khan, Edward Portnay, Narendra Singh, Steven G. Brodie, Faisal Wahid, Vladimir Santos, Thomas Knickelbine, Michael Shapiro, Madaiah Revana, Vance Wilson, Vikas Desai, Steven Hearne, Kenneth S. Hershon, Norman Lepor, Paul Ziajka, Ronald Fritz, Pratik Mondal, Alan Wiseman, John Nayda, Colby Grossman, Steven Lupovitch, Leslie B. Forgosh, Stephen Grubb, Sandeep Khurana, Sumana Gangi, Philip Nicol, William Smith, Minesh Patel, Fernando Boccalandro, Kenneth Hilty, SCOTT GABLER, Carlos Brown Sotolongo, Brian A. Bergmark, Rebecca Jordan, J Russell Strader, Sean M. Donahoe, Sumant Lamba, Catherine P. Benziger, Ahmed Arif, Wael Eid, Samer Nakhle, Faiq Akhter, Jakkidi Reddy, William L. Pomeroy, Ayotunde O. Dokun, R. D. Cohen, Drew A. Purdy, Jonathan Q. Purnell, Rakesh Prashad, Dominick Angiolillo, Michael Hafran, Kevin Deandrade, Karen Aspry, Archna Bajaj, R Miller, Lance Sloan, Chrisette Dharma, Terence Connelly, Walter Herbert Haught, Louis Kantaros, Hugh Durrence, Ira Lieber, Matthew Budoff, Mahfouz El Shahawy, Chad Travers, Ranganatha P. Potu, Mark Tannenbaum, Ira Dauber, Sharath Subramanian, Venkatesh Nadar, Mourhaf Traboulssi, Jeremy Cox, Dean Kereiakes, Luther Carter, Amit Shah, Dominic Onyema, Naim Farhat, Robert N. Schnitzler, Daniel J Humiston, Mariana Garcia-Touza, Aryan Aiyer, Michael Koren, Dinesh Arab, Matthew R. Voss, Sanjay Vora, Jose Perez, Ronald K. Mayfield, Ronald Karlsberg, Cara East, Bruce Iteld, Jonathan Fialkow, Andrew Teklinski, Marc Bernstein, Vinay Malhotra, Libby Lake, Bryan Austin, George Platt, Matthew Cavender, Nicole Pant, James Hansen, Robert McNeill, Anil Chhabra, Naseem Jaffrani, David Jones, Ayim Akyea-Djamson, Mauricio Concha, Andreas Wali, Eugenia Gianos, Cyrus Desouza, Linda Bassett Shaftoe, Alfred Tan, Josiah Zubairu, William Eaves, Eric Auerbach, Lisa Connery, Michael Jardula, David Kandath, Sam Lerman, Edward Teufel, Sabrina A Benjamin, Sandeep Bajaj, Justin Arambasick, Andrew Feldman, Axel Sigurdsson, Ingibjörg J Gudmundsdóttir, Jose C. Nicolau, Subodh Verma, LA Leiter, Ma Changsheng, Jindrich Spinar, Margus Viigimaa, Ioanna Gouni-Berthold, Jan H. Cornel, Jorge Ferreira, Hyo-soo Kim, J. Lopez-Sendon, Min‐Ji Charng, Lale Tokgozoglu, Naveed Sattar, Ron Blankstein, Jeffery L. Saver, Marc Bonaca, Rafael Diaz, Matthew Roe, Robert P. Giugliano, Erin A. Bohula, Marc S. Sabatine · 发表于：JAMA · 年份：2026 · DOI：10.1001/jama.2026.3277 · 被引用次数：16 · 研究领域：Lipoproteins and Cardiovascular Health、Atherosclerosis and Cardiovascular Diseases、Coronary Interventions and Diagnostics

Importance: Intensive lowering of low-density lipoprotein cholesterol (LDL-C) levels with PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors for cardiovascular event reduction has largely been reserved for patients with significant atherosclerosis. Objective: To investigate whether evolocumab could prevent a first major cardiovascular event (MACE) in patients without known significant atherosclerosis. Design, Setting, and Participants: VESALIUS-CV was a randomized, double-blind, placebo-controlled trial of evolocumab conducted across 774 sites in 33 countries and enrolling 12 257 patients with no prior myocardial infarction or stroke, LDL-C level 90 mg/dL or greater, and qualifying atherosclerosis or high-risk diabetes. This prespecified subgroup analysis examined outcomes in patients without known significant atherosclerosis (none of the following: prior arterial revascularization, arterial stenosis ≥50%, or coronary artery calcium score ≥100 Agatston units), all of whom had diabetes. Enrollment started in June 2019 and the last patient visit was July 2025, with a median follow-up of 4.8 years. Intervention: Patients were randomized in a 1:1 ratio to subcutaneous administration of either evolocumab (140 mg every 2 weeks) or matching placebo added to optimally tolerated statin therapy. Main Outcomes and Measures: The dual primary end points were composites of coronary heart disease death, myocardial infarction, or ischemic stroke (3-P MACE) and 3-P MACE plus isc...