Vericiguat in patients with chronic heart failure and reduced ejection fraction (VICTOR): a double-blind, placebo-controlled, randomised, phase 3 trial

Butler, J.; Mcmullan, C.J.; Anstrom, K.J.; Barash, I.; Bonaca, M.P.; Borentain, M.; Corda, S.; Ezekowitz, J.A.; Felker, G.M.; Gates, D.; Lam, C.S.P.; Lewis, E.F.; Lindenfeld, J.; Mentz, R.J.; O'Connor, C.M.; Ponikowski, P.; Reddy, Y.N.V.; Rosano, G.M.C.; Saldarriaga, C.; Senni, M.; She, L.; Teixeira, P.P.; Udelson, J.; Urbinati, A.; Vlajnic, V.; Voors, A.A.; Xing, A.; Patel, M.J.; Zannad, F.; Cadena, A.; Nunez Villota, J.; Echeverria, L.; Molina De Salazar, D.; Cavusoglu, Y.; Prozesky, H.; Silveria, F.; Zurakowski, A.; Mellado, S.; Saraiva, J.; Rodriguez Escudero, A.E.; Tsougos, E.; Cruz, G.; Accini, J.; Lakatos, F.; Freitas, A.; Noori, E.; Gould, T.; Correa Flores, R.; Scelsi, L.; Zainal Abidin, I.; Mohamed, Z.; Pandey, A.S.; Merkely, B.; Nunkoo, T.; Arana, C.; Melenovsky, V.; Zilahi, Z.; Morales, L.; Perez Rios, J.; Gosselin, G.; Salazar Lopez, H.; Cymerman, K.; Hominal, M.; Berrospi, P.; Sim, K.L.D.; Reyes Diaz, M.; Klug, E.; Montana, O.; Arakaki, D.; Troughton, R.; Konyi, A.; Pawlowicz, L.; Parent, M.; Moravsky, G.; Prokopczuk, J.; Belen Mendez Fernandez, A.; Crespo-Leiro, M.; Najjar, E.; Vico, M.; Yovaniniz, P.; Moreno, R.; Weimin, L.; Gniot, J.; Vottero, E.; Aizenberg, D.; Senni, M.; Gomez-Mesa, J.; Bayes Genis, A.; Barr, C.; Qayyum, U.; Moncada Corredor, M.; Mendez Machado, G.; Arias Mendoza, M.; Altin, C.; Prieto, J.; Mohsen, J.; Lugowski, T.; Sahin, T.; Von Lewinski, D.; Hou, A.; Toth, T.; Habon, T.; Kang, S.; Castelan Vargas, V.; Payro, G.; Skonieczny, G.; Yildirimturk, O.; Manenti, E.; Miklik, R.; Bolvanska, N.; Due Lomholdt, J.; Egstrup, K.; Briasoulis, A.; Atar, S.; Ezman Faridz Raja Shariff, R.; Vazquez, P.; Matadamas, N.; Bayram Llamas, E.; Maluenda, G.; Chen, J.; Nechvatal, L.; Belohlavek, J.; Tziakas, D.; Cabrera, J.; Ramon Gonzalez-Juanatey, J.; Janik, M.; Romero Zarante, A.; Atherton, J.; Khaykin, Y.; Lanas, F.; Xiang, G.; Busak, L.; Rieker, W.; Ben Gal, T.; Yus Haniff W Isa, W.; Chavez Michel, J.; Sudnik, W.; Lin, W.; Carlos Palma Carvajal, J.; Winkelmann, B.; Stork, S.; De Ferrari, G.; Lopez Rosas, E.; Zambrano Ruiz, E.; Cardoza Anton, L.; Vakaliuk, I.; Wong, A.; Huynh, T.; Pang, X.; Saldarriaga, C.; Wiggers, H.; Winzer, E.; Montenegro Valdovinos, P.; Caspi, O.; Sinagra, G.; Pijanowski, Z.; Zajdel, W.; Tak, B.; Bernard, D.; Bhagwat, R.; Mirna, M.; Carvajal, J.; Drasnar, T.; Schou, M.; Girerd, N.; Fan, K.; Fucili, A.; Nodari, S.; Bazzoni Ruiz, A.; Varela Varela, A.; Fajardo Campos, P.; Lu G., L.; Skoczylas, G.; Reyes Dominguez, A.; Gonzalez Costello, J.; Wilson, D.; Marcondes-Braga, F.; Echeverry, E.; Tsioufis, K.; Literati-Nagy, B.; Zwas, D.; Cho, H.; Kiam Ong, T.; Illescas Diaz, J.; Pemberton, J.; Cardona, J.; Foley, B.; Arora, P.; Mckenzie, S.; Moura, L.; Zhou, J.; Yuan, Z.; Botero, R.; Bergmann, M.; Schellong, S.; Badagliacca, R.; Arenas Leon, J.; Segura Gonzalez, A.; Morales Murillo, R.; Bobbio, E.; Huang, J.; Hsia, C.; Genc, A.; Moriarty, A.; Gunton, J.; Adlbrecht, C.; Hayami, D.; Sia, Y.; Zhao, R.; Liu, M.; Radvan, M.; Monhart, Z.; Madsen, K.; Galinier, M.; Patsilinakos, S.; Filipatos, G.; Karavidas, A.; Kirschner, R.; Kovacs, I.; Garcia, R.; Mazur, S.; Ameen Fulat, M.; Onrat, E.; Anderson, L.; Dewhurst, M.; Feldman, J.; Appiani, F.; Novajas, M.; Jiang, L.; Biao, X.; Luo, Y.; Yang, P.; Stride, N.; Vadmann, H.; Nothofer, G.; Dawood, R.; Nalbantgil, S.; Ewald, G.; Auer, J.; Allan Schaffer, S.; Ezekowitz, J.; Marin, H.; Yao, Z.; Wang, J.; Hove, J.; Alex Lee, P.; Takacs, J.; Goland, S.; Fardman, A.; Scott, A.; Witek, R.; Ntsekhe, M.; Svedberg, N.; Budoff, M.; Jaffrani, N.; Sogade, F.; Spiller, D.; Mikdadi, G.; Izzo, J.; Chan, A.; Mukherjee, A.; Lepage, S.; Peng, J.; Shen, A.; Yin, Y.; Zhang, P.; Bruun, N.; Bauer, F.; Arango Benecke, J.; Palazzuoli, A.; Choi, J.; Bang Liew, H.; Szabo-Soderberg, B.; Klantsa, A.; Petrovskyy, R.; Khadra, S.; Simoes, M.; Bourke, P.; Xiaosheng, H.; Jiang, J.; Picard, F.; Jeserich, M.; Ebelt, H.; Mittag, M.; Axthelm, C.; Ninios, V.; Rodas Diaz, M.; Han Jojo Hai, S.; Hun Kim, K.; Ricalde, A.; Turaga, M.; Szachniewicz, J.; Liu, M.; Hsieh, I.; Mordi, I.; Ariani, M.; Adler, A.; Hamroff, G.; Dharma, C.; Howlett, J.; Wang, J.; Jiang, W.; Fang, Z.; Lindhardt, M.; Kober, L.; Mewton, N.; Schwimmbeck, P.; Naka, A.; Thury, A.; Mcdonald, K.; Maloberti, A.; Jeong, J.; Sang-Ho, J.; Syukur Abdullah, A.; Wazi Ramli, A.; Medina P., F.; Miklaszewicz, B.; Huang, W.; Lindholm, C.; Olsson, A.; Chiang, C.; Lin, T.; Cassidy, C.; Gillespie, E.; Bui, H.; Schwartzmann, P.; Huang, Z.; Qiao, P.; Zhao, C.; Wang, L.; Yuan, W.; Dutoiu, T.; Frey, N.; Bauersachs, J.; Kancz, S.; Sepp, R.; Salazar Gaytan, A.; Peralta Rosado, H.; Ferrier, K.; Dhakshinamurthy, V.; Benatar, J.; Camacho, L.; Isaeva, E.; Alvarez Garcia, J.; Celik, A.; Yagensky, A.; Banerjee, P.; Michelis, K.; Bitar, F.; Zughaib, M.; Colquhoun, D.; Schober, A.; Souza, J.; Roy, A.; Miao, P.; Shaorong, W.; Cong, H.; Zhang, Q.; Likun, M.; Krejci, J.; Bronnum-Schou, J.; Tartiere, J.; Agostoni, P.; Carugo, S.; Vazquez-Tanus, J.; Kositsyn, D.; Yoong Loh, S.; Mngqibisa, R.; Coetzee, K.; Goirigolzarri Artaza, J.; Rishko, M.; Reshotko, D.; Kulyk, A.; Moore, P.; Gangasani, A.; Mcginty, J.; Doran, J.; Taheri, H.; Hariri, I.; Qureshi, A.; Papadimitriou, L.; Dib, N.; Surber, J.; Old, W.; El Shahawy, M.; Montera, M.; Bourgeois, R.; Hartleib, M.; Heffernan, M.; Moe, G.; Swiggum, E.; Jin, W.; Yanqing, W.; Huegl, B.; Sinning, J.; Triposkiadis, F.; Ziakas, A.; Benczur, B.; Nagy, A.; Murphy, R.; Goldman, A.; Volterrani, M.; Borghi, C.; Ambrosio, G.; Cho, M.; Yoo, B.; Matta Fontanet, E.; Figueroa-Torres, Y.; Meray, I.; Yakushin, S.; Rheeder, P.; Aygun, S.; Myshanych, H.; Zhurba, S.; Cooke, J.; Saxena, M.; Cadaret, L.; Funt, D.; Suarez, R.; Williams, M.; Ayalloore, S.; Jackson, R.; Lala-Trindade, A.; Duythuc To, T.; Mcquillan, B.; Pesant, Y.; Yang, Z.; Wang, J.; Liang, Q.; Qilin, M.; Hajsl, M.; Mahnkopf, C.; Hasin, T.; Toro-Grajales, I.; Rodriguez-Ospina, L.; Kastanayan, A.; Shutemova, E.; Lonnberg, I.; Lind, M.; Birhan Yilmaz, M.; Vyshnyvetskyy, I.; Rudyk, I.; Mcdonagh, T.; Jaumdally, R.; Donnelly, P.; Melucci, M.; Singh, N.; Phillips, A.; Vierecke, J.; Hotchkiss, D.; May, W.; Napoli, M.; Isseh, I.; Tabbal, G.; Mei, Y.; Guangping, L.; Berthelot, E.; Boiffard, E.; Kraemer, F.; Dorr, M.; Papp, A.; Khairani Zainal Abidin, S.; Ramirez Mendoza, M.; Godoy Palomino, A.; Volkova, E.; Khaisheva, L.; Koziolova, N.; Dronov, D.; Makotoko, E.; De Jong, D.; Barman, H.; Stets, R.; Mishchenko, L.; Trubina, S.; Ibrahim, B.; Alhaddad, M.; Isiguzo, O.; Martinez, L.; Sangrigoli, R.; Fail, P.; Chugh, A.; Viswanath, D.; Sparrow, C.; Morris, A.; Artis, A.; Mody, F.; Bostick, B.; Venugopal, V.; Verma, S.; Dong, J.; Jing, Y.; Ding, C.; Huang, K.; Ferrari, E.; Isnard, R.; Chan, N.; Chung, W.; Shvarts, Y.; Kosmacheva, E.; Lukyanov, Y.; Kovalchuk, E.; Jacovides, A.; Donets, O.; Shevchuk, S.; Kamenska, E.; Fuat, A.; Taylor, J.; Ashchi, M.; Khosla, S.; Larned, J.; Walters, C.; Martinez, J.; Mollar Fernandez, A.; Bueno Diaz, K.; Valencia, M.; Aydin, A.; Van Der Mescht, M.; Galvão, T.; Walczyk, U.; Alvarez, C.; Cristina Vicente, C.; Romero, S.; Moutafi, V.; Mino, S.; Conrado Ortega, Y.; Toth, K.; Costa, S.; Ibolya Mihaly, G.; Nortje, E.; Del Rosario Zena J., N.; Maffi, M.; Suhaimi, M.; Van Vuuren, S.; Armstrong, S.; Kósa-Hóbor, L.; Katisi, D.; Burbano, H.; Kuprova, A.; Bencze, G.; Zapata, J.; Castro Zarate, C.; Leblanc, N.; Medina Reyes, A.; Baginska-Symon, V.; Suarez, M.; Garcia, M.; Febriana, E.; Cervantes Hurtado, A.; Naidoo, V.; Cendali, G.; Gelersztein, M.; Rose, S.; Kónyi, R.; Wilczynska, J.; Brown, H.; Lapidus, I.; Bartoszewska, D.; Martinez Jaen, R.; Grille Cancela, Z.; Tronstad, I.; Giozzi, E.; Grandon, M.; Mediavilla Garcia, G.; Jing, J.; Walasek, P.; Lopez, M.; Coussio, S.; Fiorendi, L.; Trujillo, L.; Gastelurrutia, P.; Florou, A.; Reno, M.; Florez, L.; Hirata Avila, H.; Guzman Solorzano, H.; Nur Ertunc, F.; Noriega, V.; Elber, J.; Markiewicz, N.; Celik Eminoglu, G.; Rausch, V.; Duan, R.; Kovacs, S.; Levang, S.; Lee, W.; García Briones, A.; Astorga Rivas, M.; Rolirad, M.; Celik, E.; Silva, C.; Musilova, V.; Packova, H.; Niemann, K.; Hindsgaul, L.; Androutsou, E.; Nabwani, N.; Alia, N.; Maytorena, M.; Valladares, R.; Gomez Ruiz, D.; Vergara, M.; Jiang, Y.; Nechvatal, L.; Zavadilova, P.; Markakis, A.; Ariza Villanueva, C.; Rodriguez Penas, D.; Jenkins, H.; Zambrano, Y.; Lilwall, L.; Nemtean, D.; Figueroa, P.; Dai, W.; Pokorna, B.; Von Hertell, I.; Even Nir, H.; Mamat, Z.; Ruiz Rubio, E.; Matys, U.; Min Ang, K.; Olguin, V.; Müller, J.; Leyh, D.; Cuccuru, G.; Meza Hernandez, M.; Olguin Ortiz, F.; Castillo, L.; Sovtus, V.; Jones, D.; Boudreault, C.; Zhou, J.; Garcés Restrepo, C.; Leth, M.; Bosredon, C.; Aguilar Schinini, M.; Paor, G.; Ramani, F.; Chromczak, B.; Zajdel, W.; Kaygusuz, B.; Allina, J.; Winterrowd, D.; Kopp, K.; Delgado, P.; Falc, M.; Madsen, J.; Pezzi, A.; Tam, E.; Punzo, N.; Assoni, L.; Flores Pruneda, R.; Belen Garcia Gonzalez, L.; Goiz, N.; Espejo, J.; Idzikowska, P.; Carrasco Ossorio, C.; Viaplana, J.; Doughty, A.; Antunes, T.; Escruceria, A.; Karmpalioti, M.; Spandli, K.; Barhum, D.; Park, B.; Sulehan, J.; Lopez, C.; Scott, D.; Ramirez, M.; Forbus, S.; Vekariya, N.; Stibilj, K.; De Liz, F.; Mingfeng, L.; Kang, Y.; Caceres, A.; Kirchenwitz, S.; Hahn, M.; D'Alessandro, F.; Aguilar Sanchez, M.; Rosa Ramos Ruiz, A.; Soler, C.; From, K.; Chou, P.; Lee, H.; Sevim, A.; Kinnin, M.; Thomas, S.; Koehler, C.; Keller, D.; Bujold, A.; Ren, P.; Liu, M.; Machova, R.; Bouzkova, L.; Hummelshoej, J.; Rosolin, N.; Kesoglou, V.; Nikolopoulos, P.; Mandila, C.; Rozsa Toth, K.; Trautmann, D.; Del Muro Munoz, S.; Ryznar-Sicinska, A.; Mhlanga, Z.; Sahin, E.; Lyons, S.; Crawford, S.; Peek, M.; Del Rio, T.; Carcamo Medina, M.; Zhong, Y.; Gao, Y.; Wang, S.; Liu, X.; Jakobsen, E.; Nielsen, A.; Krug-Hoeren, B.; Mohamed, Z.; Yildirim, S.; Dirks, A.; Rossmaier, M.; Janz, W.; Kushnerik, Q.; Rios, S.; Zhang, X.; Ouyang, H.; Ring, L.; Ting Wang, X.; Nagy, M.; Biener, M.; Eizenberg, N.; Hulbert, C.; Augustyn, M.; Mtana, N.; Eriksson, K.; Hamal, S.; Dubois, C.; Maschenik, H.; Ferrin, S.; Alajlouni, I.; Osmond, P.; Healy, D.; Zakria, L.; Fortier, C.; Peng, X.; Wang, Y.; Liu, X.; Zhang, P.; Kragh, W.; Belkacem, N.; Garcia De Krumbach, L.; Vannuccini, F.; Jeong, H.; Wong, M.; Haglund, P.; Danyliuk, A.; Petrovskyy, T.; Muhammad, A.; Silva, V.; Toledo Grell, M.; Fang, Y.; Zhang Zhang, M.; Prunier, P.; Rupprecht, M.; Anacker, J.; Eck, K.; Schafer, B.; Ereliadou, F.; Lucía Ramírez Ávila, A.; San Lui Ho, V.; Chae, G.; González, G.; Duckworth, J.; Tunkiewicz, M.; Chou, V.; Huey-Pyng, S.; Duff, J.; Gutierrez, H.; Osmulski, T.; Solomon, A.; Assefa, M.; Sasikumar, A.; Liu, L.; Zhou, X.; Qiaochu, D.; Bang-Hansen, T.; Eriksen, E.; Tabdjoun, G.; Schumacher, J.; Gkartzonikas, I.; Kalapos, A.; Maher, J.; Algeri, M.; Gyeong Lee, R.; Kim, E.; Poh Tiew, N.; Suhaili Mamat, N.; Rodriguez Lujan, J.; Beme, A.; Norashikin Binte Fuad, S.; Broberg, M.; Rangman, B.; Chang, C.; Huang, H.; Brown, J.; Wyatt, J.; Khalil, M.; Ilana, G.; Teng, X.; Han, M.; Chen, L.; Chenyu, L.; Wang, M.; Tachot, E.; Gonzalo De Juan, M.; Schaefer, N.; Nagy, Z.; Kormanyos, A.; De La Vega, L.; Mendez, W.; Kovacs, J.; Jaques, S.; Kistanna, D.; Gil Rescavarren, M.; Sorokina, O.; Gonzalez Portilla, P.; Sahin, E.; Sichkaruk, I.; Panicker, A.; Iskandarani, R.; Culver, B.; Abidov, Y.; Macdonald, G.; Leitgeb, M.; Freire, G.; Boudreault, C.; Chen, Z.; Ruihao, L.; Zhu, C.; Tang, J.; Liu, J.; Roche, J.; Hadsund, P.; Armangau, P.; Mattavelli, I.; Famiani, R.; Galarza-Perez, J.; Kraeva, I.; Tian Chua, X.; Mosia, N.; Stuurman, C.; Sicilia Bravo, I.; Chendey, T.; Pysanko, O.; Danko, T.; Cutts, R.; Thornton, K.; Fry, N.; Blubaugh, H.; Muro, R.; Abu-Saif, A.; Bajornas, J.; Lust, M.; Killian, J.; Gilder, E.; Williams, A.; Stevens, R.; Coelho, R.; Boyd, K.; Otis, R.; Birch, M.; Fernando, C.; Lounsbury, N.; Jin, S.; Wei, W.; Barry, B.; Simons, J.; Karagogou, P.; Lathridou, P.; Annamaria, M.; Szabone Nagy, M.; Mayene Abalos, J.; Azulay, S.; Morsella, V.; Gallelli, I.; Scapicchi, C.; Gi Park, S.; Mi Shin, S.; Molina Elicier, B.; Torres-Rivas, N.; Teterina, M.; Madavha, U.; Mizrak, E.; Havryliuk, H.; Shandra, T.; Broadhead, S.; Galera, F.; Larew, C.; Mccartney Morales, P.; Socorro, E.; Hroncich, R.; Smith, V.; Jackson, R.; Evans, Y.; English, L.; Beer, N.; Sardin-Laframboise, Y.; Yu, L.; Yan, X.; Zhengzheng, N.; Ting, L.; Brindova, J.; Goebel, U.; Yedid Am, S.; Camacho-Molina, A.; Alcocer Rodriguez, L.; Evtushenko, O.; Kaverina, E.; Andersson, C.; Södergren, H.; Durhan, Ö.; Potapenko, O.; Babichev, D.; Adrego, R.; Jones, B.; Regan, S.; Lambert, S.; Ramos, M.; Phillips, A.; Schulte, J.; King, A.; Quebedeaux, A.; Reynolds, A.; Tirumanisetti, S.; Moore, L.; Liu, M.; Liu, L.; Balaya-Gouraya, L.; Derien, A.; Wied, E.; Steinbruegger, K.; Bartha, B.; Diyana Mohd Bukhari, F.; Rodriguez Cal Y Mayor, A.; Matta, M.; Volkova, E.; Garina, I.; Polyanskaya, E.; Dronov, D.; Greyling, L.; Faul, C.; Akbulut, B.; Mykhailova, I.; Rudya, G.; Trubina, S.; Harper, R.; Holman, L.; Lambert, S.; Penafiel, B.; Schwarz, L.; Parfait, V.; Alford, S.; Hayes-Jones, S.; Howarter, A.; Edmond, R.; Armstrong, K.; Strugatsky, S.; Grieshaber, V.; Adeusi, I.; Evena, A.; Wang, J.; Chen, J.; Xiaomin, L.; Xiang, D.; Zamiti-Smondel, A.; Moumni, M.; Wai Lee, K.; You, M.; Konshina, L.; Kizhvatova, N.; Yakovleva, E.; Samodurova, A.; Jacovides, T.; Shchypak, D.; Bilonko, O.; Kumpan, N.; Elphick, S.; Mellish, L.; Stamschror, L.; Hughes, L.; Fiallo, N.; Scott, N.; Cornell, A.; Hamlin, C.; Lamont, K.; Zilli, M.; Kent, C.; De Klerk, J.; Salerno, C.; Christopher, L.; Vico, M.; Mckenzie, S.; Von Lewinski, D.; Marcondes, F.; Zieroth, S.; Ducharme, A.; Lanas, F.; Junbo, G.; Gómez, J.E.; Melenovsky, V.; Wiggers, H.; Galinier, M.; Stoerk, S.; Filippatos, G.; Montenegro, P.; Lee, A.; Kancz, S.; Mcdonald, K.; Moravsky, G.; Metra, M.; Abidin, I.; Troughton, R.; Medina, F.; Vazquez-Tanus, J.; Lopatin, Y.; Sim, D.; Sliwa, K.; Cho, M.; Leiro, M.; Najjar, E.; Chiang, C.; Parkhomenko, O.; Barr, C.; Shah, P.; Budoff, M.; Greenberg, B.; Cook, T.D.; Maggioni, A.; Swedberg, K.; Wilcox, J.E.; Costanzo, M.R.; Hedlin, H.; Jones, W.S.; Alexander, K.; Al-Khatib, S.; Gutierrez, J.; Harrison, R.; Kittipibul, M.; Kolls, B.; Kong, D.; Lerman, J.; Matthews, R.; Mcgarrah, R.; Mehta, R.; Povsic, T.; Rymer, J.; Sasannejad, C.

doi:10.1016/s0140-6736(25)01665-4

Background: Vericiguat is indicated to reduce the risk of cardiovascular death and hospitalisation for heart failure in patients with heart failure and reduced ejection fraction (HFrEF) following a recent worsening event. The aim of the VICTOR trial was to assess the effect of vericiguat in patients with HFrEF without recent heart failure worsening. Methods: In this double-blind, placebo-controlled, phase 3 trial, conducted at 482 sites across 36 countries, patients aged 18 years or older with HFrEF (left ventricular ejection fraction of ≤40%) without heart failure hospitalisation within 6 months or outpatient intravenous diuretic use within 3 months before randomisation were randomly assigned (1:1) using an intervention randomisation system with interactive response technology to oral vericiguat (target 10 mg dose) or matching placebo. The primary composite endpoint was time to cardiovascular death or heart failure hospitalisation. Efficacy endpoints were assessed in the intention-to-treat population. Adverse events were assessed in all randomly assigned patients who received at least one dose of study drug (safety population). This trial is registered with ClinicalTrials.gov, NCT05093933, and is complete. Findings: Between Nov 2, 2021, and Dec 21, 2023, 10 921 patients were screened and 6105 were randomly assigned: 3053 to vericiguat and 3052 to placebo. The median age was 68·0 years (IQR 61·0-75·0), 1440 (23·6%) patients were women, 4665 (76·4%) were men, 3934 (64·4%) were White, and 2899 (47·5%) had no previous hospitalisation for heart failure. During a median follow-up of 18·5 months (IQR 13·6-24·7), primary outcome events occurred in 549 (18·0%) patients in the vericiguat group and 584 (19·1%) patients in the placebo group (hazard ratio [HR] 0·93 [95% CI 0·83-1·04]; p=0·22). As prespecified in the protocol, because the primary endpoint was not statistically significant, all analyses of secondary and exploratory endpoints are considered nominal. Cardiovascular death occurred in 292 (9·6%) patients in the vericiguat group and 346 (11·3%) patients in the placebo group (HR 0·83 [95% CI 0·71-0·97]). Hospitalisation for heart failure occurred in 348 (11·4%) patients in the vericiguat group and in 362 (11·9%) patients in the placebo group (HR 0·95 [95% CI 0·82-1·10]). Serious adverse events occurred in 717 (23·5%) of 3049 patients in the vericiguat group and 751 (24·6%) of 3049 patients in the placebo group. The most common adverse event was symptomatic hypotension (345 [11·3%] patients in the vericiguat group and 281 [9·2%] in the placebo group). All-cause death occurred in 377 (12·3%) patients in the vericiguat group and 440 (14·4%) patients in the placebo group (HR 0·84 [95% CI 0·74-0·97]). Interpretation: Among patients with HFrEF and no recent worsening, vericiguat did not reduce the risk of a composite endpoint of time to cardiovascular death or heart failure hospitalisation. Fewer cardiovascular deaths were observed in the vericiguat group than in the placebo group. Funding: Merck Sharp & Dohme (a subsidiary of Merck) and Bayer.

Vericiguat in patients with chronic heart failure and reduced ejection fraction (VICTOR): a double-blind, placebo-controlled, randomised, phase 3 trial / J. Butler, C.J. Mcmullan, K.J. Anstrom, I. Barash, M.P. Bonaca, M. Borentain, S. Corda, J.A. Ezekowitz, G.M. Felker, D. Gates, C.S.P. Lam, E.F. Lewis, J. Lindenfeld, R.J. Mentz, C.M. O'Connor, P. Ponikowski, Y.N.V. Reddy, G.M.C. Rosano, C. Saldarriaga, M. Senni, L. She, P.P. Teixeira, J. Udelson, A. Urbinati, V. Vlajnic, A.A. Voors, A. Xing, M.J. Patel, F. Zannad, A. Cadena, J. Nunez Villota, L. Echeverria, D. Molina De Salazar, Y. Cavusoglu, H. Prozesky, F. Silveria, A. Zurakowski, S. Mellado, J. Saraiva, A.E. Rodriguez Escudero, E. Tsougos, G. Cruz, J. Accini, F. Lakatos, A. Freitas, E. Noori, T. Gould, R. Correa Flores, L. Scelsi, I. Zainal Abidin, Z. Mohamed, A.S. Pandey, B. Merkely, T. Nunkoo, C. Arana, V. Melenovsky, Z. Zilahi, L. Morales, J. Perez Rios, G. Gosselin, H. Salazar Lopez, K. Cymerman, M. Hominal, P. Berrospi, K.L.D. Sim, M. Reyes Diaz, E. Klug, O. Montana, D. Arakaki, R. Troughton, A. Konyi, L. Pawlowicz, M. Parent, G. Moravsky, J. Prokopczuk, A. Belen Mendez Fernandez, M. Crespo-Leiro, E. Najjar, M. Vico, P. Yovaniniz, R. Moreno, W. Li, J. Gniot, E. Vottero, D. Aizenberg, M. Senni, J. Gomez-Mesa, A. Bayes Genis, C. Barr, U. Qayyum, M. Moncada Corredor, G. Mendez Machado, M. Arias Mendoza, C. Altin, J. Prieto, J. Mohsen, T. Lugowski, T. Sahin, D. Von Lewinski, A. Hou, T. Toth, T. Habon, S. Kang, V. Castelan Vargas, G. Payro, G. Skonieczny, O. Yildirimturk, E. Manenti, R. Miklik, N. Bolvanska, J. Due Lomholdt, K. Egstrup, A. Briasoulis, S. Atar, R. Ezman Faridz Raja Shariff, P. Vazquez, N. Matadamas, E. Bayram Llamas, G. Maluenda, J. Chen, L. Nechvatal, J. Belohlavek, D. Tziakas, J. Cabrera, J. Ramon Gonzalez-Juanatey, M. Janik, A. Romero Zarante, J. Atherton, Y. Khaykin, F. Lanas, X. Gu, L. Busak, W. Rieker, T. Ben Gal, W. Yus Haniff W Isa, J. Chavez Michel, W. Sudnik, W. Lin, J. Carlos Palma Carvajal, B. Winkelmann, S. Stork, G. De Ferrari, E. Lopez Rosas, E. Zambrano Ruiz, L. Cardoza Anton, I. Vakaliuk, A. Wong, T. Huynh, X. Pang, C. Saldarriaga, H. Wiggers, E. Winzer, P. Montenegro Valdovinos, O. Caspi, G. Sinagra, Z. Pijanowski, W. Zajdel, B. Tak, D. Bernard, R. Bhagwat, M. Mirna, J. Carvajal, T. Drasnar, M. Schou, N. Girerd, K. Fan, A. Fucili, S. Nodari, A. Bazzoni Ruiz, A. Varela Varela, P. Fajardo Campos, L. Lu G., G. Skoczylas, A. Reyes Dominguez, J. Gonzalez Costello, D. Wilson, F. Marcondes-Braga, E. Echeverry, K. Tsioufis, B. Literati-Nagy, D. Zwas, H. Cho, T. Kiam Ong, J. Illescas Diaz, J. Pemberton, J. Cardona, B. Foley, P. Arora, S. Mckenzie, L. Moura, J. Zhou, Z. Yuan, R. Botero, M. Bergmann, S. Schellong, R. Badagliacca, J. Arenas Leon, A. Segura Gonzalez, R. Morales Murillo, E. Bobbio, J. Huang, C. Hsia, A. Genc, A. Moriarty, J. Gunton, C. Adlbrecht, D. Hayami, Y. Sia, R. Zhao, M. Liu, M. Radvan, Z. Monhart, K. Madsen, M. Galinier, S. 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Vericiguat in patients with chronic heart failure and reduced ejection fraction (VICTOR): a double-blind, placebo-controlled, randomised, phase 3 trial

Butler, Javed;McMullan, Ciaran J;Anstrom, Kevin J;Barash, Irina;Bonaca, Marc P;Borentain, Maria;Corda, Stefano;Ezekowitz, Justin A;Felker, G Michael;Gates, Davis;Lam, Carolyn S P;Lewis, Eldrin F;Lindenfeld, JoAnn;Mentz, Robert J;O'Connor, Christopher M;Ponikowski, Piotr;Reddy, Yogesh N V;Rosano, Giuseppe M C;Saldarriaga, Clara;Senni, Michele;She, Lilin;Teixeira, Pedro Pinto;Udelson, James;Urbinati, Alessia;Vlajnic, Vanja;Voors, Adriaan A;Xing, Aiwen;Patel, Mahesh J;Zannad, Faiez;Cadena, Alberto;Nunez Villota, Julio;Echeverria, Luis;Molina De Salazar, Dora;Cavusoglu, Yuksel;Prozesky, Hans;Silveria, Fabio;Zurakowski, Aleksander;Mellado, Sergio;Saraiva, Jose;Rodriguez Escudero, Aldo Edwin;Tsougos, Elias;Cruz, German;Accini, Jose;Lakatos, Ferenc;Freitas, Aguinaldo;Noori, Ebrahim;Gould, Trevor;Correa Flores, Roger;Scelsi, Laura;Zainal Abidin, Imran;Mohamed, Zarinah;Pandey, A. Shekhar;Merkely, Bela;Nunkoo, Theema;Arana, Camilo;Melenovsky, Vojtech;Zilahi, Zsolt;Morales, Luis;Perez Rios, Jesus;Gosselin, Gilbert;Salazar Lopez, Hector;Cymerman, Krzysztof;Hominal, Miguel;Berrospi, Percy;Sim, Kheng Leng David;Reyes Diaz, Melissa;Klug, Eric;Montana, Oscar;Arakaki, Diego;Troughton, Richard;Konyi, Attila;Pawlowicz, Lidia;Parent, Marie-Claude;Moravsky, Gil;Prokopczuk, Janusz;Belen Mendez Fernandez, Ana;Crespo-Leiro, Maria;Najjar, Emil;Vico, Marisa;Yovaniniz, Patricio;Moreno, Raul;Li, Weimin;Gniot, Jacek;Vottero, Ezequiel;Aizenberg, Diego;Senni, Michele;Gomez-Mesa, Juan;Bayes Genis, Antoni;Barr, Craig;Qayyum, Usman;Moncada Corredor, Miguel;Mendez Machado, Gustavo;Arias Mendoza, Maria;Altin, Cihan;Prieto, Juan;Mohsen, Jameel;Lugowski, Tomasz;Sahin, Tayfun;Von Lewinski, Dirk;Hou, Aijie;Toth, Tunde;Habon, Tamas;Kang, Seok-Min;Castelan Vargas, Victor;Payro, Gerardo;Skonieczny, Grzegorz;Yildirimturk, Ozlem;Manenti, Euler;Miklik, Roman;Bolvanska, Nora;Due Lomholdt, Jens;Egstrup, Kenneth;Briasoulis, Alexandros;Atar, Shaul;Ezman Faridz Raja Shariff, Raja;Vazquez, Paul;Matadamas, Norberto;Bayram Llamas, Edmundo;Maluenda, Gabriel;Chen, Jiyan;Nechvatal, Libor;Belohlavek, Jan;Tziakas, Dimitrios;Cabrera, Jose;Ramon Gonzalez-Juanatey, Jose;Janik, Matthew;Romero Zarante, Angela;Atherton, John;Khaykin, Yaariv;Lanas, Fernando;Gu, Xiang;Busak, Ladislav;Rieker, Werner;Ben Gal, Tuvia;Yus Haniff W Isa, W;Chavez Michel, Jaime;Sudnik, Wanda;Lin, Weiqin;Carlos Palma Carvajal, Juan;Winkelmann, Bernhard;Stork, Stefan;De Ferrari, Gaetano;Lopez Rosas, Enrique;Zambrano Ruiz, Eduardo;Cardoza Anton, Luisa;Vakaliuk, Igor;Wong, Aaron;Huynh, Thao;Pang, Xiaohua;Saldarriaga, Clara;Wiggers, Henrik;Winzer, Ephraim;Montenegro Valdovinos, Pablo;Caspi, Oren;Sinagra, Gianfranco;Pijanowski, Zbigniew;Zajdel, Wojciech;Tak, Bahar;Bernard, David;Bhagwat, Ravi;Mirna, Moritz;Carvajal, Juan;Drasnar, Tomas;Schou, Morten;Girerd, Nicolas;Fan, Katherine;Fucili, Alessandro;Nodari, Savina;Bazzoni Ruiz, Alberto;Varela Varela, Alberto;Fajardo Campos, Pedro;Lu G. , Libia;Skoczylas, Grzegorz;Reyes Dominguez, Antonio;Gonzalez Costello, Jose;Wilson, David;Marcondes-Braga, Fabiana;Echeverry, Eduardo;Tsioufis, Konstantinos;Literati-Nagy, Botond;Zwas, Donna;Cho, Hyun-Jai;Kiam Ong, Tiong;Illescas Diaz, Jesus;Pemberton, James;Cardona, Jose;Foley, Brian;Arora, Pankaj;Mckenzie, Scott;Moura, Lidia;Zhou, Jingmin;Yuan, Zuyi;Botero, Rodrigo;Bergmann, Martin;Schellong, Sebastian;Badagliacca, Roberto;Arenas Leon, Jose;Segura Gonzalez, Armando;Morales Murillo, Ronald;Bobbio, Emanuele;Huang, Jin-Long;Hsia, Chien-Hsun;Genc, Ahmet;Moriarty, Andrew;Gunton, James;Adlbrecht, Christopher;Hayami, Doug;Sia, Ying;Zhao, Ruiping;Liu, Mingya;Radvan, Martin;Monhart, Zdenek;Madsen, Kristian;Galinier, Michel;Patsilinakos, Sotirios;Filipatos, Gerasimos;Karavidas, Apostolos;Kirschner, Robert;Kovacs, Istvan;Garcia, Ricardo;Mazur, Stanislaw;Ameen Fulat, Muhammed;Onrat, Ersel;Anderson, Lisa;Dewhurst, 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Alanna;Artis, Andre;Mody, Freny;Bostick, Brian;Venugopal, Vineet;Verma, Subodh;Dong, Jianzeng;Yu, Jing;Ding, Chunhua;Huang, Kai;Ferrari, Emile;Isnard, Richard;Chan, Ngai-Yin;Chung, Wook-Jin;Shvarts, Yury;Kosmacheva, Elena;Lukyanov, Yury;Kovalchuk, Evgeniy;Jacovides, Andrew;Donets, Oleksandra;Shevchuk, Sergii;Kamenska, Ellina;Fuat, Ahmet;Taylor, Justin;Ashchi, Majdi;Khosla, Sandeep;Larned, Joshua;Walters, Christopher;Martinez, Jessica;Mollar Fernandez, Anna;Bueno Diaz, Karen;Valencia, Maria;Aydin, Akin;Van Der Mescht, Marelize;Galvão, Tamyres;Walczyk, Urszula;Alvarez, Claudia;Cristina Vicente, Carla;Romero, Sonia;Moutafi, Vasiliki;Mino, Sebastian;Conrado Ortega, Yineth;Toth, Krisztina;Costa, Sandra;Ibolya Mihaly, Gyongyver;Nortje, Engela;Del Rosario Zena J. , Norma;Maffi, Marta;Suhaimi, Manhaiyun;Van Vuuren, Sonnika;Armstrong, Samantha;Kósa-Hóbor, Laura;Katisi, Debora;Burbano, Hector;Kuprova, Anna;Bencze, Gabriella;Zapata, Jessica;Castro Zarate, Carlos;Leblanc, Nathalie;Medina Reyes, America;Baginska-Symon, Violetta;Suarez, Martin;Garcia, Maria;Febriana, Eveline;Cervantes Hurtado, Adriana;Naidoo, Vaman;Cendali, Gloria;Gelersztein, Miriam;Rose, Stephanie;Kónyi, Réka;Wilczynska, Joanna;Brown, Helene;Lapidus, Ira;Bartoszewska, Dorota;Martinez Jaen, Ruben;Grille Cancela, Zulaica;Tronstad, Isabel;Giozzi, Erica;Grandon, Marcela;Mediavilla Garcia, Guiomar;Jing, Junsheng;Walasek, Pawel;Lopez, Marcia;Coussio, Santiago;Fiorendi, Laura;Trujillo, Laura;Gastelurrutia, Paloma;Florou, Alexandra;Reno, Marie;Florez, Leisa;Hirata Avila, Haydea;Guzman Solorzano, Hannah;Nur Ertunc, Fatma;Noriega, Viviana;Elber, Jenny;Markiewicz, Natalia;Celik Eminoglu, Gizem;Rausch, Viktoria;Duan, Ruili;Kovacs, Szilvia;Levang, Szilvia;Lee, Wonmi;García Briones, Ana;Astorga Rivas, Marcos;Rolirad, Monika;Celik, Ebrar;Silva, Carollainy;Musilova, Veronika;Packova, Helena;Niemann, Kari;Hindsgaul, Linda;Androutsou, Evangelia;Nabwani, Neda;Alia, Nur;Maytorena, Maria;Valladares, Regina;Gomez Ruiz, Delia;Vergara, Maria;Jiang, Yihan;Nechvatal, Libor;Zavadilova, Petra;Markakis, Alexandros;Ariza Villanueva, Carola;Rodriguez Penas, Diego;Jenkins, Hailey;Zambrano, Yenisca;Lilwall, Lydia;Nemtean, Debbie;Figueroa, Pamela;Dai, Wenjuan;Pokorna, Blanka;Von Hertell, Ines;Even Nir, Hadas;Mamat, Zalida;Ruiz Rubio, Elena;Matys, Urszula;Min Ang, Kah;Olguin, Veronica;Müller, Julia;Leyh, Daniela;Cuccuru, Giuditta;Meza Hernandez, Michelle;Olguin Ortiz, Felipe;Castillo, Leonila;Sovtus, Volodymyra;Jones, Deborah;Boudreault, Caroline;Zhou, Jiali;Garcés Restrepo, Claudia;Leth, Marianne;Bosredon, Cecile;Aguilar Schinini, Mayra;Paor, Galit;Ramani, Federica;Chromczak, Bozena;Zajdel, Wojciech;Kaygusuz, Burcu;Allina, Jorge;Winterrowd, Donna;Kopp, Kristen;Delgado, Paola;Falc, Matej;Madsen, Jette;Pezzi, Agnes;Tam, Eva;Punzo, Noemi;Assoni, Luca;Flores Pruneda, Rosa;Belen Garcia Gonzalez, Luz;Goiz, Nazareth;Espejo, Jill;Idzikowska, Paulina;Carrasco Ossorio, Catalina;Viaplana, Judith;Doughty, Angela;Antunes, Talita;Escruceria, Adriana;Karmpalioti, Maria;Spandli, Katalin;Barhum, Dema;Park, Boram;Sulehan, Juriah;Lopez, Claudia;Scott, Deborah;Ramirez, Maite;Forbus, Sabrina;Vekariya, Nehal;Stibilj, Kathryn;De Liz, Fernanda;Lu, Mingfeng;Kang, Yuhong;Caceres, Aleydy;Kirchenwitz, Stephanie;Hahn, Mario;D'Alessandro, Francesca;Aguilar Sanchez, Ma.;Rosa Ramos Ruiz, Ana;Soler, Cristina;From, Kristina;Chou, Ping-Ping;Lee, Hsiao-Ting;Ak, Sevim;Kinnin, Michelle;Thomas, Simeoni;Koehler, Cordula;Keller, Deborah;Bujold, Amelie;Ren, Peiyan;Liu, Mingya;Machova, Renata;Bouzkova, Lenka;Hummelshoej, Joan;Rosolin, Nathalie;Kesoglou, Vaggelitsa-Eirini;Nikolopoulos, Petros;Mandila, Christina;Rozsa Toth, Karolyne;Trautmann, Dora;Del Muro Munoz, Sergio;Ryznar-Sicinska, Anna;Mhlanga, Zandi;Sahin, Ebru;Lyons, Sinead;Crawford, Susan;Peek, Madeline;Del Rio, Tatiana;Carcamo Medina, Macarena;Zhong, Yuxin;Gao, Yue;Wang, Siqi;Liu, Xuejiao;Jakobsen, Emilie;Nielsen, Annette;Krug-Hoeren, Bianca;Mohamed, Zakariyyaa;Yildirim, Selin;Dirks, Anne;Rossmaier, Manuela;Janz, Wendy;Kushnerik, Quentin;Rios, Sebastian;Zhang, Xiying;Ouyang, Huijun;Ring, Lotte;Ting Wang, Xue;Nagy, Monika;Biener, Meital;Eizenberg, Nava;Hulbert, Cathy;Augustyn, Marta;Mtana, Noloyiso;Eriksson, Kristina;Hamal, Sajad;Dubois, Crystal;Maschenik, Heather;Ferrin, Smelda;Alajlouni, Ibraheem;Osmond, Peter;Healy, Denise;Zakria, Lubna;Fortier, Carl;Peng, Xiaomei;Wang, Yutao;Liu, Xuejun;Zhang, Peng;Kragh, Winnie;Belkacem, Nassima;Garcia De Krumbach, Lissette;Vannuccini, Francesca;Jeong, Hwayoung;Wong, Mabelle;Haglund, Pernilla;Danyliuk, Andrii;Petrovskyy, Taras;Muhammad, Ali;Silva, Veronica;Toledo Grell, Maribel;Fang, Yao;Zhang Zhang, Mengqing;Prunier, Philippe;Rupprecht, Mariana;Anacker, Jelena;Eck, Kerstin;Schafer, Benjamin;Ereliadou, Foteini;Lucía Ramírez Ávila, Andrea;San Lui Ho, Venus;Chae, Gaeul;González, Geraldine;Duckworth, Jamie;Tunkiewicz, Monika;Chou, Vinny;Su, Huey-Pyng;Duff, Jackie;Gutierrez, Haydee;Osmulski, Teresa;Solomon, Alison;Assefa, Mihret;Sasikumar, Anusha;Liu, Lin;Zhou, Xiaowei;Du, Qiaochu;Bang-Hansen, Therese;Eriksen, Elsebet;Tabdjoun, Ghoulem;Schumacher, Jeanette;Gkartzonikas, Ilias;Kalapos, Anita;Maher, Joanne;Algeri, Michela;Gyeong Lee, Ryeong;Kim, Eun;Poh Tiew, Neoh;Suhaili Mamat, Nurul;Rodriguez Lujan, Jeanneth;Beme, Anna;Norashikin Binte Fuad, Siti;Broberg, Malin;Rangman, Birgitta;Chang, Chiao-Wen;Huang, Hui-Ling;Brown, Joanna;Wyatt, Jaime;Khalil, Mohamed;Ilana, Gabriela;Teng, Xiaoli;Han, Mizozhu;Chen, Liping;Lv, Chenyu;Wang, Min;Tachot, Emilie;Gonzalo De Juan, Maria;Schaefer, Nicole;Nagy, Zsolt;Kormanyos, Arpad;De La Vega, Lucia;Mendez, Wendy;Kovacs, Jo-Anne;Jaques, Sharon;Kistanna, Danica;Gil Rescavarren, Maria;Sorokina, Olga;Gonzalez Portilla, Paz;Sahin, Emel;Sichkaruk, Iryna;Panicker, Abeesh;Iskandarani, Rema;Culver, Breanna;Abidov, Yulia;Macdonald, Gemma;Leitgeb, Maria-Christine;Freire, Grazielle;Boudreault, Caroline;Chen, Zhenfei;Li, Ruihao;Zhu, Chuangting;Tang, Jia;Liu, Jinxiu;Roche, 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Stephanie;Hayes-Jones, Sharyce;Howarter, April;Edmond, Robert;Armstrong, Kimberly;Strugatsky, Svetlana;Grieshaber, Vickie;Adeusi, Iluyomade;Evena, Akhila;Wang, Jiajia;Chen, Jinxia;Lu, Xiaomin;Xiang, Danli;Zamiti-Smondel, Amina;Moumni, Manel;Wai Lee, Kar;You, Miju;Konshina, Larisa;Kizhvatova, Natalia;Yakovleva, Elena;Samodurova, Anna;Jacovides, Tracy;Shchypak, Diana;Bilonko, Oksana;Kumpan, Nataliia;Elphick, Sandra;Mellish, Lisa;Stamschror, Lauren;Hughes, Leigha;Fiallo, Natalie;Scott, Nicole;Cornell, Alexandra;Hamlin, Constance;Lamont, Katie;Zilli, Martina;Kent, Christi;De Klerk, Jaco;Salerno, Christina;Christopher, Lydia;Vico, Marisa;McKenzie, Scott;von Lewinski, Dirk;Marcondes, Fabiana;Zieroth, Shelley;Ducharme, Anique;Lanas, Fernando;Ge, Junbo;Gómez, Juan Esteban;Melenovsky, Vojtech;Wiggers, Henrik;Galinier, Michel;Stoerk, Stefan;Filippatos, Gerasimos;Montenegro, Pablo;Lee, Alex;Kancz, Sandor;McDonald, Ken;Moravsky, Gil;Metra, Marco;Abidin, Imran;Troughton, Richard;Medina, Felix;Vazquez-Tanus, Jose;Lopatin, Yury;Sim, David;Sliwa, Karen;Cho, Myeong-Chan;Leiro, Marisa;Najjar, Emil;Chiang, Chern-En;Parkhomenko, Oleksandr;Barr, Craig;Shah, Palak;Budoff, Matthew;Greenberg, Barry;Cook, Tom D.;Maggioni, Aldo;Swedberg, Karl;Wilcox, Jane E.;Costanzo, Maria Rosa;Hedlin, Haley;Jones, W. Schuyler;Alexander, Karen;Al-Khatib, Sana;Gutierrez, Jorge;Harrison, Robert;Kittipibul, Mark;Kolls, Bradley;Kong, David;Lerman, Joseph;Matthews, Robert;McGarrah, Robert;Mehta, Rajendra;Povsic, Thomas;Rymer, Jennifer;Sasannejad, Cina

2025

Abstract

Background: Vericiguat is indicated to reduce the risk of cardiovascular death and hospitalisation for heart failure in patients with heart failure and reduced ejection fraction (HFrEF) following a recent worsening event. The aim of the VICTOR trial was to assess the effect of vericiguat in patients with HFrEF without recent heart failure worsening. Methods: In this double-blind, placebo-controlled, phase 3 trial, conducted at 482 sites across 36 countries, patients aged 18 years or older with HFrEF (left ventricular ejection fraction of ≤40%) without heart failure hospitalisation within 6 months or outpatient intravenous diuretic use within 3 months before randomisation were randomly assigned (1:1) using an intervention randomisation system with interactive response technology to oral vericiguat (target 10 mg dose) or matching placebo. The primary composite endpoint was time to cardiovascular death or heart failure hospitalisation. Efficacy endpoints were assessed in the intention-to-treat population. Adverse events were assessed in all randomly assigned patients who received at least one dose of study drug (safety population). This trial is registered with ClinicalTrials.gov, NCT05093933, and is complete. Findings: Between Nov 2, 2021, and Dec 21, 2023, 10 921 patients were screened and 6105 were randomly assigned: 3053 to vericiguat and 3052 to placebo. The median age was 68·0 years (IQR 61·0-75·0), 1440 (23·6%) patients were women, 4665 (76·4%) were men, 3934 (64·4%) were White, and 2899 (47·5%) had no previous hospitalisation for heart failure. During a median follow-up of 18·5 months (IQR 13·6-24·7), primary outcome events occurred in 549 (18·0%) patients in the vericiguat group and 584 (19·1%) patients in the placebo group (hazard ratio [HR] 0·93 [95% CI 0·83-1·04]; p=0·22). As prespecified in the protocol, because the primary endpoint was not statistically significant, all analyses of secondary and exploratory endpoints are considered nominal. Cardiovascular death occurred in 292 (9·6%) patients in the vericiguat group and 346 (11·3%) patients in the placebo group (HR 0·83 [95% CI 0·71-0·97]). Hospitalisation for heart failure occurred in 348 (11·4%) patients in the vericiguat group and in 362 (11·9%) patients in the placebo group (HR 0·95 [95% CI 0·82-1·10]). Serious adverse events occurred in 717 (23·5%) of 3049 patients in the vericiguat group and 751 (24·6%) of 3049 patients in the placebo group. The most common adverse event was symptomatic hypotension (345 [11·3%] patients in the vericiguat group and 281 [9·2%] in the placebo group). All-cause death occurred in 377 (12·3%) patients in the vericiguat group and 440 (14·4%) patients in the placebo group (HR 0·84 [95% CI 0·74-0·97]). Interpretation: Among patients with HFrEF and no recent worsening, vericiguat did not reduce the risk of a composite endpoint of time to cardiovascular death or heart failure hospitalisation. Fewer cardiovascular deaths were observed in the vericiguat group than in the placebo group. Funding: Merck Sharp & Dohme (a subsidiary of Merck) and Bayer.

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				Settore MEDS-07/B - Malattie dell'apparato cardiovascolare
			
	Data di pubblicazione
	
				2025
			
	Data ahead of print o data di stampa
	
				30-ago-2025
			
	Rivista in ANCE
	
				THE LANCET
			
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				https://dx.doi.org/10.1016/s0140-6736(25)01665-4
			
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