Dual endothelin antagonist aprocitentan for resistant hypertension (PRECISION): a multicentre, blinded, randomised, parallel-group, phase 3 trial
| العنوان: | Dual endothelin antagonist aprocitentan for resistant hypertension (PRECISION): a multicentre, blinded, randomised, parallel-group, phase 3 trial |
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| المؤلفون: | Markus P Schlaich, Marc Bellet, Michael A Weber, Parisa Danaietash, George L Bakris, John M Flack, Roland F Dreier, Mouna Sassi-Sayadi, Lloyd P Haskell, Krzysztof Narkiewicz, Ji-Guang Wang, Christopher Reid, Markus Schlaich, Ivor Katz, Andrew Ajani, Sinjini Biswas, Murray Esler, Grahame Elder, Simon Roger, David Colquhoun, John Mooney, Tine De Backer, Alexandre Persu, Martin Chaumont, Jean-Marie Krzesinski, Thomas Vanassche, Ginette Girard, Lew Pliamm, Ernesto Schiffrin, Fatima Merali, George Dresser, Michel Vallee, Shivinder Jolly, Stephen Chow, Jiguang Wang, Jianjun Mu, Jing Yu, Hong Yuan, Yingqing Feng, Xin Zhang, Jianhong Xie, Ling Lin, Miroslav Soucek, Jiri Widimsky, Renata Cifkova, Jan Vaclavik, Martin Ullrych, Martin Lukac, Ivan Rychlik, Thomas Guldager Lauridsen, Ilkka Kantola, Jyrki Taurio, Olavi Ukkola, Olivier Ormezzano, Philippe Gosse, Michel Azizi, Pierre-Yves Courand, Pascal Delsart, Jean Michel Tartiere, Felix Mahfoud, Roland Schmieder, Johannes Stegbauer, Philipp Lurz, Michael Koziolek, Christian Ott, Nicole Toursarkissian, Konstantinos Tsioufis, Konstantinos Kyfnidis, Athanasios Manolis, Sotirios Patsilinakos, Pantelis Zebekakis, Apostolos Karavidas, Pall Denes, Katalin Bezzegh, Marianna Zsom, Laszlo Kovacs, Yehonatan Sharabi, Mazen Elias, Ivetta Sukholutsky, Chaim Yosefy, Irina Kenis, Shaul Atar, Massimo Volpe, Muiesan Maria Lorenza, Stefano Taddei, Guido Grassi, Franco Veglio, Jung Woo Son, Jang-Young Kim, Joong-Il Park, Chang Hoon Lee, Hae-Young Lee, Rasa Raugaliene, Jolanta Elena Marcinkeviciene, Roma Kavaliauskiene, Jaap Deinum, Abraham Kroon, Bert-Jan van den Born, Andrzej Januszewicz, Andrzej Tykarski, Jolanta Walczewska, Zbigniew Gaciong, Andrzej Wiecek, Marzena Chrostowska, Andrzej Kleinrok, Jan Krekora, Grzegorz Kania, Anna Podrazka-Szczepaniak, Cezary Golawski, Maciej Podziewski, Barbara Kaczmarek, Grzegorz Skoczylas, Andrzej Wilkolaski, Iwona Wozniak, Marzena Janik-Palazzolo, Barbara Rewerska, Aleksandra Konradi, Yuriy Shvarts, Tamara Pecherina, Konstantin Nikolaev, Gapon Liudmila, Olga Orlikova, Viktor Mordovin, Natalia Petrochenkova, Gadel Kamalov, Elena Kosmacheva, Vadim Tyrenko, Vladimir Gorbunov, Andrey Obrezan, Tatiana Supryadkina, Irina Ler, Oleg Kotenko, Anatoly Kuzin, Fernando Martínez García, Josep Redon, Anna Oliveras, Luis Beltran Romero, Valerii Shatylo, Leonid Rudenko, Andriy Bazylevych, Yurii Rudyk, Oleksandr Karpenko, Mykola Stanislavchuk, Vira Tseluyko, Mykola Kushnir, Ervin Asanov, Yuriy Sirenko, Andriy Yagensky, David Collier, Pankaj Gupta, David Webb, Mary MacLeod, James McLay, Aaron Peace, Samir Arora, Patricia Buchanan, Robert Harris, Ronald Degarmo, Mario Guillen, Adam Karns, Joel Neutel, Yogesh Paliwal, Karlton Pettis, Phillip D. Toth, Jeffrey M. Wayne, Michael Bain Butcher, Phillip M. Diller, Suzanne Oparil, David Calhoun, Donald Brautigam, John Flack, Jesse M. Goldman, Arash Rashidi, Nabeel Aslam, William Haley, Nabil Andrawis, Brian Lang, Randy Miller, James Powell, Robert Dewhurst, James Pritchard, Dinesh Khanna, Dennis Tang, Nashwa Gabra, Jean Park, Conigliaro Jones, Cranford Scott, Blanca Luna, Murtaza Mussaji, Ravi Bhagwat, Michael Bauer, John McGinty, Rajesh Nambiar, Renee Sangrigoli, William Ross Davis, William Eaves, Frank McGrew, Ahmed Awad, Eric Bolster, David Scott, Paramjit Kalirao, Pascal Dabel, Wesley Calhoun, Steven Gouge, Mark Warren, Mary Katherine Lawrence, Aamir Jamal, Mohamed El-Shahawy, Carlos Mercado, Jayant Kumar, Pedro Velasquez-Mieyer, Robert Busch, Todd Lewis, Lisa Rich |
| المساهمون: | Public and occupational health, Vascular Medicine, ACS - Atherosclerosis & ischemic syndromes, APH - Global Health, APH - Personalized Medicine, ACS - Heart failure & arrhythmias, Schlaich, M, Bellet, M, Weber, M, Danaietash, P, Bakris, G, Flack, J, Dreier, R, Sassi-Sayadi, M, Haskell, L, Narkiewicz, K, Wang, J, Reid, C, Katz, I, Ajani, A, Biswas, S, Esler, M, Elder, G, Roger, S, Colquhoun, D, Mooney, J, De Backer, T, Persu, A, Chaumont, M, Krzesinski, J, Vanabsche, T, Girard, G, Pliamm, L, Schiffrin, E, Merali, F, Dresser, G, Vallee, M, Jolly, S, Chow, S, Mu, J, Yu, J, Yuan, H, Feng, Y, Zhang, X, Xie, J, Lin, L, Soucek, M, Widimsky, J, Cifkova, R, Vaclavik, J, Ullrych, M, Lukac, M, Rychlik, I, Guldager Lauridsen, T, Kantola, I, Taurio, J, Ukkola, O, Ormezzano, O, Gosse, P, Azizi, M, Courand, P, Delsart, P, Tartiere, J, Mahfoud, F, Schmieder, R, Stegbauer, J, Lurz, P, Koziolek, M, Ott, C, Toursarkissian, N, Tsioufis, K, Kyfnidis, K, Manolis, A, Patsilinakos, S, Zebekakis, P, Karavidas, A, Denes, P, Bezzegh, K, Zsom, M, Kovacs, L, Sharabi, Y, Elias, M, Sukholutsky, I, Yosefy, C, Kenis, I, Atar, S, Volpe, M, Lorenza, M, Taddei, S, Grassi, G, Veglio, F, Son, J, Kim, J, Park, J, Lee, C, Lee, H, Raugaliene, R, Marcinkeviciene, J, Kavaliauskiene, R, Deinum, J, Kroon, A, van den Born, B, Januszewicz, A, Tykarski, A, Walczewska, J, Gaciong, Z, Wiecek, A, Chrostowska, M, Kleinrok, A, Krekora, J, Kania, G, Podrazka-Szczepaniak, A, Golawski, C, Podziewski, M, Kaczmarek, B, Skoczylas, G, Wilkolaski, A, Wozniak, I, Janik-Palazzolo, M, Rewerska, B, Konradi, A, Shvarts, Y, Pecherina, T, Nikolaev, K, Liudmila, G, Orlikova, O, Mordovin, V, Petrochenkova, N, Kamalov, G, Kosmacheva, E, Tyrenko, V, Gorbunov, V, Obrezan, A, Supryadkina, T, Ler, I, Kotenko, O, Kuzin, A, Martinez, F, Redon, J, Oliveras, A, Beltran Romero, L, Shatylo, V, Rudenko, L, Bazylevych, A, Rudyk, Y, Karpenko, O, Stanislavchuk, M, Tseluyko, V, Kushnir, M, Asanov, E, Sirenko, Y, Yagensky, A, Collier, D, Gupta, P, Webb, D, Macleod, M, Mclay, J, Peace, A, Arora, S, Buchanan, P, Harris, R, Degarmo, R, Guillen, M, Karns, A, Neutel, J, Paliwal, Y, Pettis, K, Toth, P, Wayne, J, Butcher, B, Diller, P, Oparil, S, Calhoun, D, Brautigam, D, Goldman, J, Rashidi, A, Aslam, N, Haley, W, Andrawis, N, Lang, B, Miller, R, Powell, J, Dewhurst, R, Pritchard, J, Khanna, D, Tang, D, Gabra, N, Jones, C, Scott, C, Luna, B, Mussaji, M, Bhagwat, R, Bauer, M, Mcginty, J, Nambiar, R, Sangrigoli, R, Ross Davis, W, Eaves, W, Mcgrew, F, Awad, A, Bolster, E, Scott, D, Kalirao, P, Dabel, P, Calhoun, W, Gouge, S, Warren, M, Lawrence, M, Jamal, A, El-Shahawy, M, Mercado, C, Kumar, J, Velasquez-Mieyer, P, Busch, R, Lewis, T, Rich, L |
| المصدر: | The Lancet (London), 400, 1927-1937 The Lancet, 400(10367), 1927-1937. Elsevier Limited The Lancet (London), 400, 10367, pp. 1927-1937 |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Endothelin Receptor Antagonists, Treatment Outcome, Double-Blind Method, Hypertension, Vascular damage Radboud Institute for Health Sciences [Radboudumc 16], Humans, General Medicine, Blood Pressure Monitoring, Ambulatory, resistant hypertension, Dual endothelin antagonist aprocitentan, Antihypertensive Agents |
| الوصف: | Contains fulltext : 286841.pdf (Publisher’s version ) (Closed access) BACKGROUND: Resistant hypertension is associated with increased cardiovascular risk. The endothelin pathway has been implicated in the pathogenesis of hypertension, but it is currently not targeted therapeutically, thereby leaving this relevant pathophysiological pathway unopposed with currently available drugs. The aim of the study was to assess the blood pressure lowering efficacy of the dual endothelin antagonist aprocitentan in patients with resistant hypertension. METHODS: PRECISION was a multicentre, blinded, randomised, parallel-group, phase 3 study, which was done in hospitals or research centres in Europe, North America, Asia, and Australia. Patients were eligible for randomisation if their sitting systolic blood pressure was 140 mm Hg or higher despite taking standardised background therapy consisting of three antihypertensive drugs, including a diuretic. The study consisted of three sequential parts: part 1 was the 4-week double-blind, randomised, and placebo-controlled part, in which patients received aprocitentan 12·5 mg, aprocitentan 25 mg, or placebo in a 1:1:1 ratio; part 2 was a 32-week single (patient)-blind part, in which all patients received aprocitentan 25 mg; and part 3 was a 12-week double-blind, randomised, and placebo-controlled withdrawal part, in which patients were re-randomised to aprocitentan 25 mg or placebo in a 1:1 ratio. The primary and key secondary endpoints were changes in unattended office systolic blood pressure from baseline to week 4 and from withdrawal baseline to week 40, respectively. Secondary endpoints included 24-h ambulatory blood pressure changes. The study is registered on ClinicalTrials.gov, NCT03541174. FINDINGS: The PRECISION study was done from June 18, 2018, to April 25, 2022. 1965 individuals were screened and 730 were randomly assigned. Of these 730 patients, 704 (96%) completed part 1 of the study; of these, 613 (87%) completed part 2 and, of these, 577 (94%) completed part 3 of the study. The least square mean (SE) change in office systolic blood pressure at 4 weeks was -15·3 (SE 0·9) mm Hg for aprocitentan 12·5 mg, -15·2 (0·9) mm Hg for aprocitentan 25 mg, and -11·5 (0·9) mm Hg for placebo, for a difference versus placebo of -3·8 (1·3) mm Hg (97·5% CI -6·8 to -0·8, p=0·0042) and -3·7 (1·3) mm Hg (-6·7 to -0·8; p=0·0046), respectively. The respective difference for 24 h ambulatory systolic blood pressure was -4·2 mm Hg (95% CI -6·2 to -2·1) and -5·9 mm Hg (-7·9 to -3·8). After 4 weeks of withdrawal, office systolic blood pressure significantly increased with placebo versus aprocitentan (5·8 mm Hg, 95% CI 3·7 to 7·9, p |
| وصف الملف: | application/pdf; STAMPA |
| تدمد: | 0140-6736 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a8661784163094e06b4019a9c7edb043Test http://hdl.handle.net/2066/286841Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....a8661784163094e06b4019a9c7edb043 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 01406736 |
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