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Cardiovascular Safety of Degarelix Versus Leuprolide in Patients With Prostate Cancer: The Primary Results of the PRONOUNCE Randomized Trial

2021; Lippincott Williams & Wilkins; Volume: 144; Issue: 16 Linguagem: Inglês

10.1161/circulationaha.121.056810

1524-4539

Renato D. Lópes, Celestia S. Higano, Susan F. Slovin, Adam J. Nelson, Robert Bigelow, Per Settergren Sørensen, Chiara Melloni, Shaun G. Goodman, Christopher P. Evans, Jan Nilsson, Deepak L. Bhatt, Noel W. Clarke, Tine Kold Olesen, Belinda T. Doyle-Olsen, Henriette Kristensen, Lauren Arney, Matthew T. Roe, John H. Alexander, Mirjam Mol-Arts, Samreen Mansor-Lefebvre, Konstantin Zubovskiy, Allan Blemings, Klaus A. Dugi, Gerald S. Bloomfield, Chris Kontos, Adam D. DeVore, J. Dedrick Jordan, Brad J. Kolls, J. B. Matthews, Rajendra H. Mehta, Thomas J. Povsic, Michael Morse, Kenneth W. Mahaffey, Susan Halabi, Darryl P. Leong, Laurence Klotz, Neil Fleshner, G. Kenneth Jansz, Jonathan Giddens, R. Blair Egerdie, Joseph L. Chin, Joseph Zadra, Richard Casey, Jean Simard, Tamim Niazi, André‐Guy Martin, Marek Babjuk, Jaroslav Hájek, Jiří Klečka, Jiří Kubeš, Jan Schraml, Jitka Jakesova, J Vaňásek, Bohuslav Melichar, Heikki Seikkula, M. Abdiche, Marc Colombel, P. Debourdeau, G. Robert, Arnauld Villers, Guillaume Ploussard, Benjamin Pradère, F. Bruyère, Jean‐Luc Descotes, I. Ouzaïd, Alexander Winter, Herbert Hanitzsch, H. Sperling, Ralf Eckert, Peter Hammerer, E. Stagge, F. Seseke, Silvio Szymula, Aristotelis Bamias, A. Thanos, Konstantinos Hatzimouratidis, Charalambos Mamoulakis, Haralabos P. Kalofonos, Elżbieta Oszukowska, Katarzyna Madziarska, Jacek Fijuth, Mateusz Obarzanowski, B. Yа. Alekseev, Vagif Atduev, Pushkar' DIu, Evgeniy Veliev, A. V. Zyryаnov, С Б Петров, Evgeny Kopyltsov, Vadim Kozlov, Ladislav Macko, J. Dúbravický, Richard Polak, Obaidullah Mir, Marek Vargovcak, I. Minčík, J. Kliment, Frederico Gonçalves, J Mikuláš, Roman Sokol, Michal Korček, Jozef Marko, Viktor Kováčik, Igor Milichovsky, P. Dubinský, J. Michael Lazarus, Sanjay Dixit, Euan Green, Rajaguru Srinivasan, Danish Mazhar, Yeung Ng, Naveed Sarwar, Craig Herman, Frederick Snoy, Robert Given, Ronald Suh, David Lipsitz, James L. Bailen, Lawrence Gervasi, Idalia Acosta, Laurence Belkoff, Ning Wu, Jeffrey A. Frankel, Lawrence I. Karsh, Bryant Poole, David Lieber, Jason Engel, Mohamed Bidair, Steven Rosenberg, Paul Sieber, Adam Perzin, Susan Kalota, Amar Singh, Ralph A. Henderson, Jeffrey D. Wayne, Moben Mirza, Richard D’Anna, Fredrick Wolk, Osvaldo Padron, Kathryn Bylow, Jonathan Rubenstein, Benjamin A. Gartrell, Michael Schwartz, Kalpesh Patel, Ajit Maniam, Thomas E. Keane, Michael Goodman, Charles Bane, Michael Jae-Yoon Chung, Stephen J. Savage, Edward Uchio, Minh Son Nguyen, William J. Aronson, Rakesh Khanna, Carlton Barnswell,

Cancer, Lipids, and Metabolism

The relative cardiovascular safety of gonadotropin-releasing hormone (GnRH) antagonists compared with GnRH agonists in men with prostate cancer and known atherosclerotic cardiovascular disease remains controversial.In this international, multicenter, prospective, randomized, open-label trial, men with prostate cancer and concomitant atherosclerotic cardiovascular disease were randomly assigned 1:1 to receive the GnRH antagonist degarelix or the GnRH agonist leuprolide for 12 months. The primary outcome was the time to first adjudicated major adverse cardiovascular event (composite of death, myocardial infarction, or stroke) through 12 months.Because of slower-than-projected enrollment and fewer-than-projected primary outcome events, enrollment was stopped before the 900 planned participants were accrued. From May 3, 2016, to April 16, 2020, a total of 545 patients from 113 sites across 12 countries were randomly selected. Baseline characteristics were balanced between study groups. The median age was 73 years, 49.8% had localized prostate cancer; 26.3% had locally advanced disease, and 20.4% had metastatic disease. A major adverse cardiovascular event occurred in 15 (5.5%) patients assigned to degarelix and 11 (4.1%) patients assigned to leuprolide (hazard ratio, 1.28 [95% CI, 0.59-2.79]; P=0.53).PRONOUNCE (A Trial Comparing Cardiovascular Safety of Degarelix Versus Leuprolide in Patients With Advanced Prostate Cancer and Cardiovascular Disease) is the first, international, randomized clinical trial to prospectively compare the cardiovascular safety of a GnRH antagonist and a GnRH agonist in patients with prostate cancer. The study was terminated prematurely because of the smaller than planned number of participants and events, and no difference in major adverse cardiovascular events at 1 year between patients assigned to degarelix or leuprolide was observed. The relative cardiovascular safety of GnRH antagonists and agonists remains unresolved. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02663908.