Lorundrostat in Participants With Uncontrolled Hypertension and Treatment-Resistant Hypertension

作者：Manish Saxena, Luke J. Laffin, Claudio Borghi, Beatriz Fernandez, Jalal K. Ghali, Branko Kopjar, Krishna R. Polu, Simon D. Roger, Brian Taylor Slingsby, Frank Strutz, Liffert Vogt, Matthew R. Weir, David Rodman, Launch-HTN Investigators, John Mark Joyce, Nandita Joshi Jones, Sujeeta Dhakhwa, Susan Angel, Fadi Chalhoub, Leticia Goodwin, Tatyana Miroshnikova, Patricia Ann W. Brown, Robert Molpus, Felipe Suplicy, Beckie Klipper, Keung Lee, Andrew Chow, Karla Alfonsin, Becky Hogan, Lon Lynn, Paul Lunseth, Alexandra Lynch, Andres Patron, George Kaleel Rafeedie, M Izquierdo Patrón, И. Н. Лукьянов, George Rafeedie, John Lentz, Luis A. Diaz-Secades, E M Cantero Perez, Damarys Sacasa, Leticia Jimenez, Yadiel Sanchez, Atul Chugh, Jai Radhakrishnan, Vijay U. Rao, Kaitlin Ziedonis, Ayanna Guzman-Nguyen, Lora McGill, Lisa Usdan, Valerie Arnold, Carolyn Scatamacchia, Keerthi Heckle, Codi M. Anthony, Melissa Flowers, Henry Punzi, Kathy Cassidy, Waymon Drummond, John M. Flack, Farrell O. Mendelsohn, James Powell, Hunter Coore, Nakeydia Bryant, Farah Madhani-Lovely, Sujatha Pitani, Angela Dunlap, Amanda Merlino, Alexis Steele-Griffen, Charles H. Crump, Scott Harnsberger, Alexander White, Richard P. Marshall, B. Visvalingam, Viviana Hargis, Richard Mohammed, Nora Borello, Joseph Soufer, Malgorzata Chustecka, Jillian Reid, Amanda Pacheco, Nashwa Gabra, Magda Hanna, Josefina Manalo, Roccio Harbison, R Markan, Lianette Ramos, Carl Diener, Vicki Kalen, Enrique Cifuentes, Shawn G. Platt, Carly Widup, Nayeli Lopez, Dilwar Ajani, Caroline Mbogua, Minhas Ladiwala, D. Galvez Oviedo, Mario C. Reyes, Carl E. Dukes, Pragati Choudhary, Michael E. Dunn, R Anderson, Ariana Bauer, Brian Hollis, Alexandra Suslow, Melissa Frampton, Antonio M. Mendes, Tara Strandwitz, Sonia Thompson, Michael McCartney, Marc Shay, MaryBeth Sampson, Joanne Monaghan, Madeline J. Puracchio, A. Tänzer, Michael J. McCartney, Deborah M. Green, Christa Riekert, Ramana Puppala, Marshall Nash, Ambreen Hamid, Arvind Krishna, Hedi Daugherty, Erica Ness, Manuchehr Darani, Ashley Duzik, Hikyhe Ogannesian, Claire Presswood, Elias S. Siraj, Barbara Rizzardi, V. Abad, Ashlee Wright, Deirdre McMullen, Hilary Spears, Graciela López, Kenneth I. Maynard, A. Prasad, Annie Raphael, William R. Davis, Jaynier Moya Hechevarria, Jayler Valde Hechevarria, Ronoel Penalver, Mariela Manzanares Angulo, Yuniarka Garcia, Marwan Kaskas, Sreedhara B. Alla, Yeona DaCosta Auld, Mary Lawrence, Sabrina Boyte, M. Montoro Lopez, Yogesh Paliwal, Amit Paliwal, Mia Curtis, Sarah Gordon, Yebin Kwon, Bassel Ashouri, Nidal Morrar, Geoffrey Lipscomb, Christine Fuller, Stanley Koch, Meg Imig, Sarah Wildenradt, Heather Akins, Adam Kaplan, Angelique Ferraris, M Tarlac, David DeAtkine, Michael R. Adams, Margarita Nunez, David Estes, Dionne Clarke, Mohammed Allaw, Chelsea Miles, Melody Werne, Joseph Newburg, Laura Pearlman, S. M. Rutter, J. McCormick, Aamir Jamal, D N Gandhi, Rajan Sibu, Brandon Bonilla, S.T. Cox, Shanda Gower, Angela Genovese, Sharee Wright, Samantha Ting, Nelson Kopyt, Jennifer Bashour, Debbie Bridges, Cristina Puig-Saus, Angela Okolie, Elisa Swieboda, Stephanie L. Smith, Akber Safder, Beatriz Colon, Anand Irimpen, Mark R. Warren, Regina Dodis, Matthew Hager, Tonni Gortman, Mohan Kesani, Carol M. Budgin, Holly Mechling, Adam Karns, Sarom Hong, Edith Sisneros, Vishweshwar Ranga, Maya Pudi, Ahmed Awad, William K. Smith, Kristin D. Morgan, John D. Mahan, Robert J. Noveck, Lauren Degregoria, T Gray, Ronald Stumbris, Taran Parmar, Paul Beckett, Gary Soucie, Berta Bates, Jerry Punch, Richard L. Gibson, Jennifer Winbigler, Elizabeth Parker, Hunter Cooper, Savannah Kidd, Linda Carol Johnson, Oscar Linn, Stephee Haun, Cyndi Puckett, L. E. Reed, Mavis Matsumoto, Julie Braun, Krishanthi Jayathilaka, Jennifer Hines, Ramy J. Toma, Samantha Williams, Meghan Golson, William Kirby, Jazmine Henry, Adrienne Baltscheit, Harold Bays, Taylor Codey, Barbara Ritchey, David R. Liljenquist, Anil Chhabra, Michael W. Gates, Sarah Dobrosky, John Hanley, Rani Rabah, Audrey Jones, Paul D. Hartley, Kenneth S. Hershon, Dennis Lewis, Clarisa Baltazar, Billy Hour, Veronica Macias, Citlali Garcia, Pascal Dabel, Jehad Haggiagi, Jocelyn Marin, José F. Cardona, Evelio H. Sosa, Rainer Pacheco, Brian MacGillivray, Randall H. Schuster, Abha Gyani, G Boyd, Heather M.‐L. Miller, Norma Saenz, Pink Folmar, Hayes T. Williams, Latorya Franks, Faheem Shaikh, Deidra Meredith, Tzu-Jen Tzao, Gee Perez, Jeffrey D. Wayne, Esther Gayoba, Tammy Ward, Jalal K. Ghali, Olusola Gbinigie, Rambod Rouhbakhshh, John B. Johnson, Tameka Fortune, Robert Brahan, Leah Prentiss, David Butuk, Janelle Poole, Scott Frisby, Taylor Conrad, Carlos Sariol-Curbelo, Neira I. Segarra-Ortiz, Nestor R. Gonzalez, Jennifer Ringrose, Stephen Chow, Ronald Ahkras, Richard Assef, Elise Irani, Anthony Olofintuyi, Mary Joan MacLeod, German Guzman Gutierrez, David Counter, Sandra Williams, Manish Saxena, David Collier, Armida Balawon, F. Galera, Arooj Ayub, M. Z. Butt, Munirah Islam, Rahat Uddin, Joseph Cheriyan, Spoorthy Kulkarni, James Goodman, Pablo Kostelec, Sahan Mendis, C Hey, Sarah Rayne, Richard A. Gaunt, Christine Voss, Teresa Connolly, Indranil Dasgupta, Pauline A. Swift, Rebecca Suckling, Mona Wahba, Laijee Benny, Paula-Jane Marrett, Michael Waldron, Jan Knobloch, Ronan Sheehan, Maisie Rowe, Syazrah Salam, Nicholas Jacobsen, Rutesh Patel, Linsay McCallum, Bryony Martin, Maggie Rostron, Ramandeep Gill, H.D. King, Jonathan Garstang, Simon Macartney, Sally Feltham, Timothy Doulton, Lawrence J. Barnes, Susan Keast, Robert Allen, Nicola Donlin, Ruth Graham, Andreas P. D. Hajineocli, Dominique Stéphan, Antoine Cremer, Christophe Mariat, B. Franko, M. Ducret, Etienne Cellot, Déborah Chaintreuil, Antoine Metzger, Ivona Milic, Isabelle Rey, Mathilde Pibarot, Sandra Jost-Turillot, Blandine Lafitte, Olivier Moranne, Kerstin Sturm, Peter Hahn, Sascha Öhm, Suganthi Luci Magimaiseelan, Saskia Kerschischnik, Peter Heymer, Jan Winkler, A.-R. Günzel, Lars Raddatz, Nadine Voß, Markus van der Giet, Alla Reimer, Khalida Sidigy, Jan Wagner, Annette Weerda, Belinda Ehrhardt, U. Rudolph, Rolf Wachter, Franziska Loricke, Thomas Jung, Nikolaus Jung, Anja Kruszek, Andreas Pfuetzner, Karl Fengler, Andreia Serrano, Fernando Jaén Águila, José Ramón González‐Juanatey, Pilar Mazón Ramos, Diego Iglesias Álvarez, José Seijas‐Amigo, Fernando Martínez García, María José Forner, Alba Morales Cano, Nicolás Roberto Robles Pérez-Monteoliva, Álvaro Álvarez, Juan Villa Rincon, Rafael Santamaría, M.V. Pendón Ruiz de Mier, Ana Isabel Soria Robles, Cristian Rodelo, Isabel López, Maria Victoria Pendon, Andres Carmona Rubio, Alberto Ortíz, Nieves Martell Claros, Egidio Imbalzano, Aurora Lo Porto, Marianna Chiappalone, Massimo Volpe, Luana Orlando, Marianna Gigliotti De Fazio, Cristina Panico, Giuliano Tocci, Giulia Nardoianni, Giovanni Marco Dutti, Emanuele Barbato, Marco Russo, Gianluca Campo, Marta Belmonte, María Lorenza Muiesan, Paolo Cimaglia, Matteo Serenelli, Elisa Mosele, Giuseppe Boriani, Riccardo Sarzani, Agostino Virdis, Davide Maremmani, Ferdinando De Negri, Elisabetta Fini, Giovanni Gori, Elisa Iacopini, Guido Iaccarino, Francesca Viazzi, Lucia Macciò, Michela Piaggio, Giuseppe Chirco, Rita Del Pinto, Alessandro Maloberti, Amedeo Mugellini, Claudio Borghi, Arrigo F.G. Cicero, Davide Agnoletti, Federica Piani, Gianluca Rubini, Chiara Grassi, Federica Fogacci, Maurizio Volterrani, Jaap Deinum, Liffert Vogt, Wafa Karar, Marlon van de Putte, Wilko Spiering, Simone C.C. Hartong, Ralitsa Pancheva, Iskren Garvanski, Goritsa Borisova, Nikolay Iliev, Krasimira Tsoneva, Daniel Trendafilov, M. A. Tsvetkova, I. Denev, M Stoyanov, Daniel Lyubenov, Борислав Борисов, Mariya Hristova, Vladmir Zhelev, Ivaylo Ivanov, В. Иванов, K. Kancheva, Kiril Petrov, Gabriela Tseneva, Barbara Rewerska, Maciej Podziewski, Artur Artemuk, Ewa Satora, Iwona Chrostek, Grzegorz Skoczylas, Stanisław Pilowski, Dominika Oszejko, Grzegorz Kania, Maciej Kania, Ewa Okonska-Jagoda, Milena Guz-Kawka, Agata Kuziemska, Justyna Pedowska‐Włoszek, Joanna Dziuda, Aleksandra Rosiak-Kawka, Anna Foder, Maciej Żechowicz, Paulina Nowek, Marta Drankowska-Bendorf, Michał Smoliński, Wioletta Żechowicz, M. Konieczny, Jolanta Kitowska-Koterla, Katarzyna Bartnicka-Maslowska, Maciej Kotwica, Andrzej Bissinger, Magdalena Jander, Beata Wojciechowska, Joanna Szczepankowska, Andrzej Więcek, Agata Kujawa-Szewieczek, Natalia Słabiak-Błaż, Theodora Benedek, Codrut Ioan Ciurea, Raluca Maria Laculiceanu, Raluca Elena Ouatu, Ștefan Moț, Minodora Andor, Valentina Gabriela Ciobotaru, Elena Divna Muresan, Cristiana Bustea, Mihaela Ivan, Adrian Apostol, Carina Bogdan, Oana Sandu, Petru Marius Turcan, Tiberiu Liviu Dragomir, Andreea Rachieru, Olguta Octavia Vasile, Gabriela Palade, Elisabeta Bădilă, Cristina Florescu, Petre Ciobanu, Simona Daniela Neamțu, A Paraschiv, Ranjit Rasalam, Munro Neville, Victoria Husk, Rebecca Waterfield, Shelley Westgarth-Nugent, Markus Schlaich, Sayeh Heidari Nejad, Damon A. Bell, Omar Azzam, Akash Sharma, Anu Joyson, Simon D. Roger, Viduranga Wijeratne, Ferdinandus de Looze, Eniko Ujvary, Ian Chi Kei Wong, Leonie Kelly, Kristi McLendon, Peter Hay, Andrew Hung, James Bennett, Elijah McKee, Nathan Dwyer, Christopher Levi, Thomas M. Polasek, Michael Harrison, Robert C. Scott, Stephanie Wallace, Amy Morrison, Alan Parnham, Jagadeesh Kurtkoti, Yusuf Eqbal, Bianca Garcia, Elif I. Ekinci, Nupoor Tomar, Frank Gao, Cecila Pham, Alexander Yao, Jasmin Seah, T. Redman · 发表于：JAMA · 年份：2025 · DOI：10.1001/jama.2025.9413 · 被引用次数：87 · 研究领域：Hormonal Regulation and Hypertension、Blood Pressure and Hypertension Studies、Sodium Intake and Health

Importance: Uncontrolled hypertension remains a global health concern and dysregulated aldosterone production is a central mechanism. Lorundrostat, a novel aldosterone synthase inhibitor that reduces aldosterone production, demonstrated efficacy in participants with uncontrolled hypertension, including those with treatment-resistant hypertension. Objective: To evaluate the efficacy and safety of lorundrostat for lowering blood pressure (BP) when added to a prescribed regimen of 2 to 5 antihypertensive medications in adults with uncontrolled hypertension and treatment-resistant hypertension. Design, Setting, and Participants: In this phase 3, randomized clinical trial, adults with uncontrolled hypertension, including those with treatment-resistant hypertension, were enrolled between November 2023 and September 2024 at 159 clinic sites across 13 countries. The last date of follow-up was January 24, 2025. Intervention: Randomization ratio of 1:2:1 to 50 mg/d of lorundrostat for 6 weeks followed by 100 mg/d of lorundrostat for 6 weeks (n = 270) if they met prespecified criteria, 50 mg/d of lorundrostat for 12 weeks (n = 541), or daily placebo for 12 weeks (n = 272). The prespecified criteria included systolic BP of 130 mm Hg or greater, potassium level of 4.8 mmol/L or less, sodium level of 135 mmol/L or greater, an estimated glomerular filtration rate (eGFR) of greater than 45 mL/min/1.73 m2, and less than a 25% reduction in eGFR. Main Outcome and Measures: The primary outcome w...