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    Spironolactone versus placebo in patients undergoing maintenance dialysis - ACHIEVE: an international, parallel-group, randomised controlled trial
    (Elsevier BV, 2025-08)
    Michael Walsh
    ;
    David Collister
    ;
    Martin Gallagher
    ;
    Patrick B Mark
    ;
    Janak R de Zoysa
    ;
    Jessica Tyrwhitt
    ;
    Karthik Tennankore
    ;
    Gilmar Reis
    ;
    Denis Xavier
    ;
    Wen J Liu
    ;
    Li Zuo
    ;
    Amanda Y Wang
    ;
    FELIX GALLEGOS, CAMILO EDGAR VINICIO  
    ;
    Laura Sola
    ;
    Mustafa Arici
    ;
    Russell Villanueva
    ;
    Vivekanand Jha
    ;
    Dalton Précoma
    ;
    Christian G Rabbat
    ;
    Sheik Sulthan Alavudeen
    ;
    Atiya R Faruqui
    ;
    LOPEZ FLECHER, MAVEL ESTEFANIA  
    ;
    Lonnie Pyne
    ;
    Ron Wald
    ;
    Fei Yuan
    ;
    Kumar Balasubramanian
    ;
    Shun Fu Lee
    ;
    Alena Kuptsova
    ;
    Courtney Christou
    ;
    P J Devereaux
    ;
    PJ Devereaux
    ;
    Michael Walsh
    ;
    Mustafa Arici
    ;
    Janak R. de Zoysa
    ;
    Martin Gallagher
    ;
    FELIX GALLEGOS, CAMILO EDGAR VINICIO  
    ;
    Vivekanand Jha
    ;
    Wen J. Liu
    ;
    Patrick B. Mark
    ;
    Gilmar Reis
    ;
    Laura Sola
    ;
    Karthik Tennankore
    ;
    Russell Villanueva
    ;
    Ron Wald
    ;
    Amanda Y. Wang
    ;
    Denis Xavier
    ;
    Li Zuo
    ;
    Johannes F.E. Mann
    ;
    Andrew Smyth
    ;
    David Collister
    ;
    Thiago Ferreira
    ;
    Mats Junek
    ;
    David Massicotte-Azarniouch
    ;
    Pavel Roshanov
    ;
    Emma Wu
    ;
    Nan Ye
    ;
    Patrick Parfrey
    ;
    Stuart Pocock
    ;
    Marc Pfeffer
    ;
    Marcello Tonelli
    ;
    David Jayne
    ;
    Angela Webster
    ;
    Sandip Mitra
    ;
    Akram Al-Gabry
    ;
    Jessica Tyrwhitt
    ;
    Courtney Christou
    ;
    Alena Kuptsova
    ;
    Kaitlyn McKay
    ;
    Colin Hardy
    ;
    Coleen Lapensee
    ;
    Joanne Wilkinson
    ;
    Kayla Pohl
    ;
    Katie Ou-Yang
    ;
    Heidi Wilton
    ;
    Kieran Commanda
    ;
    Matthew Smart
    ;
    Fei Yuan
    ;
    John Liu
    ;
    Shun Fu Less
    ;
    Peggy Gao
    ;
    Kumar Balasubramanian
    ;
    Mark Molec
    ;
    Emily Dai
    ;
    Dilani Wijesena
    ;
    Martin Renters
    ;
    Nidhi Jethoo
    ;
    Angela Wang
    ;
    Yachna Mehta
    ;
    Victoria Gregory
    ;
    Jannel Ramos
    ;
    Jayeeta Chakraborty
    ;
    Ayesha Malik
    ;
    Pratiti Ghosh
    ;
    Hong Man
    ;
    Sarah Coggan
    ;
    Rosemary Oliveira
    ;
    Andrea Mazzetti
    ;
    Ida Yue
    ;
    Joe Zhou
    ;
    LOPEZ FLECHER, MAVEL ESTEFANIA  
    ;
    Akshaya R. Faruqui
    ;
    Freeda Xavier
    ;
    Preeti Girish
    ;
    Remya Giriraju
    ;
    Susan Subbin
    ;
    Jagannath Rao
    ;
    Mary Baker
    ;
    Lyndel Rive
    ;
    Lynsey Gillespie
    ;
    Emma Moody
    ;
    Shannon Fairley
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    Sophie Mason
    ;
    Diann Taggart
    ;
    Pamela Surtees
    ;
    Elizabeth Douglas
    ;
    Samantha Carmichael
    ;
    Pauline Branley
    ;
    Scott Campbell
    ;
    Victoria Campbell
    ;
    Melissa Cheetham
    ;
    Yeoung Cho
    ;
    Adam Flavell
    ;
    Celine Foote
    ;
    Ross Francis
    ;
    Muh Geot Wong
    ;
    Nicholas Gray
    ;
    Jeffrey Ha
    ;
    Peter Hollett
    ;
    Meg Jardine
    ;
    Joanna Kent
    ;
    John Killen
    ;
    Rathika Krishnasamy
    ;
    Wan Chan Lai
    ;
    Vicki Levidiotis
    ;
    Fahim Magid
    ;
    Kumar Mahadevan
    ;
    Lucy McMullen
    ;
    David Mudge
    ;
    Euan Noble
    ;
    Dharmenaan Palammuthusingam
    ;
    Eugenia Pedagogos
    ;
    Kevan Polkinghorne
    ;
    Samantha Putrino
    ;
    Mona Razavian
    ;
    Angus Ritchie
    ;
    Shaundeep Sen
    ;
    Yvonne Shen
    ;
    Amanda Siriwardana
    ;
    Girish Talaulikar
    ;
    Carolyn VanEps
    ;
    Giles Walters
    ;
    Jane Waugh
    ;
    Martin Wolley
    ;
    Roger Wyndham
    ;
    Andre Alvarenga
    ;
    Veronica Antunes
    ;
    Cassiano Augusto Cray da Costa
    ;
    Marcello Bacci
    ;
    Gilberto Baroni
    ;
    Lilian Belinaso
    ;
    Isabela Boehm
    ;
    Viviane Calice da Silva
    ;
    Soraia Cantini
    ;
    Thiara Cardon de Oliveira
    ;
    Miguel Carlos Riella
    ;
    Sarah Castro
    ;
    Cristina Paula Correa
    ;
    Patricia da Cruz Queiroz
    ;
    Poliana da Silva Correia
    ;
    Antonio de Padua Lanna
    ;
    Luiza de Souza
    ;
    Gracielly de Souza Pantano
    ;
    Thais Dias
    ;
    Suellen Dias Rodrigues
    ;
    Mauro Hernandes
    ;
    Thais Ferreira Dias
    ;
    Lucas Filogonio
    ;
    Marisa Franca Ferreira
    ;
    Roberto Franco
    ;
    Ricardo Furtado de Carvalho
    ;
    Joao Goldani
    ;
    Victor A. Hamamotto Sato
    ;
    Marina Hanauer
    ;
    Valerio Hipólito
    ;
    Carlos A. Kenji Makashima
    ;
    Iara Mafra
    ;
    Gusthavo Mandelli
    ;
    Giulliana Marcal
    ;
    Carlos Marmanillo
    ;
    Helena Martin
    ;
    Lucas Melo
    ;
    Samira Miquelanti Terto
    ;
    Gina Moreno Gordon
    ;
    Precil Neves
    ;
    Alexania Nicolodi
    ;
    Geraldo Paula
    ;
    Aline Pedros dos Santos
    ;
    Gerson Pereira Junior
    ;
    Ana Picolli
    ;
    Dalton Précoma
    ;
    Patricia Queiroz
    ;
    Humberto Rebello Narcizo
    ;
    Camila Richter
    ;
    Henrique Rogognete
    ;
    Stephanie Santana
    ;
    Adriana F.M. Schuinski
    ;
    Gabriella Sevignani
    ;
    Rafael Furtado Silva
    ;
    Fernando Thome
    ;
    Maria Jose Tostes
    ;
    Meire Yokota
    ;
    Sergio Zimmermann
    ;
    Mohsen Agharazii
    ;
    William Beaubien-Souligny
    ;
    Aminu Bello
    ;
    Daniel Blum
    ;
    Josee Bouchard
    ;
    Scott Brimble
    ;
    Vanbric Casilla
    ;
    Joslyn Conley
    ;
    Sacha DeSerres
    ;
    Simon Desmeules
    ;
    Brian Forzley
    ;
    Louis Girard
    ;
    German Gonzalez
    ;
    Ziv Harel
    ;
    John Paul Harmon
    ;
    Brenda Hemmelgarn
    ;
    Swapnil Hiremath
    ;
    Rachel Holden
    ;
    Abeed Jamal
    ;
    Mercedeh Kiaii
    ;
    Bryce Kiberd
    ;
    Abhijat Kitchlu
    ;
    Jean Philippe Lafrance
    ;
    Danny Lagrotteria
    ;
    Louis-Philippe Laurin
    ;
    Adeera Levin
    ;
    Scott Lyle
    ;
    Francois Madore
    ;
    Braden Manns
    ;
    Marie Michaud
    ;
    Amber Molnar
    ;
    Norman Muirhead
    ;
    Annie-Claire Nadeau-Fredette
    ;
    Gihad Nesrallah
    ;
    Stuart Netherton
    ;
    Amy Nistico
    ;
    Carley Ouellet
    ;
    Neesh Pannu
    ;
    Jeffrey Perl
    ;
    Vincent Pichette
    ;
    Lonnie Pyne
    ;
    Christian Rabbat
    ;
    Jean-Philippe Rioux
    ;
    Joanna Sasal
    ;
    Nairne Scott-Douglas
    ;
    Steven Soroka
    ;
    Rita Suri
    ;
    Siva Thanamayooran
    ;
    Karthik Tennankore
    ;
    Benjamin Thomson
    ;
    Michel Vallee
    ;
    Ron Wald
    ;
    Matthew Weir
    ;
    Deborah Zimmerman
    ;
    Li Zuo
    ;
    Lianhua Chen
    ;
    Menghua Chen
    ;
    Yuqing Chen
    ;
    Feng Gao
    ;
    Li Gao
    ;
    Chunxiang Guo
    ;
    Yi Guo
    ;
    Yan Jing
    ;
    Rongshan Li
    ;
    Guojuan Zhang
    ;
    Qian Zhang
    ;
    Zhongxiang Zhang
    ;
    X Xinglei Zhou
    ;
    Doris Almeida
    ;
    Santiago Carrasco
    ;
    Ignacio Martinez
    ;
    Mayra Sanchez
    ;
    Sandra Valarezo
    ;
    Vladimir Vizcaino
    ;
    Faizan Ahmad Abdul Irfan Ansari
    ;
    Alan Almeida
    ;
    YJ Anupama
    ;
    Swaminathan Balamurugan
    ;
    Irshad Basheer
    ;
    Rammohan Bhat
    ;
    Thanigachalam Dineshkumar
    ;
    Rohan Divivedi
    ;
    Payal Gaggar
    ;
    Natarajan Gopalakrishnan
    ;
    Kiranmai Ismal
    ;
    Velmurugan Jeeva
    ;
    Ajish John
    ;
    Janardhana Kamath
    ;
    Manjunath Kulkarni
    ;
    Vinod Kumar
    ;
    Abhijith Magal
    ;
    Mali Manish
    ;
    Rajendran Manorajan
    ;
    Sonu Manuael
    ;
    Limesh Marisiddappa
    ;
    Chandralekha Netharakere
    ;
    Abraham Oomman
    ;
    Rajendran Padmaraj
    ;
    Aashish Parekha
    ;
    Potturi Pragna
    ;
    Devaraju Premkumar
    ;
    Prashant V. Rahate
    ;
    Ganapathy Raja
    ;
    C. Rakesh Durai
    ;
    Satish Rao
    ;
    Madipalli Ravitej
    ;
    Manisha Sahay
    ;
    Ramanathan Sakthirajan
    ;
    Pradeep Shenoy
    ;
    Dakshinamoorthy Shiva Kumar
    ;
    DG Shivakumar
    ;
    Rasika Sirsat
    ;
    D. Sree Bhushan Raju
    ;
    Rajanna Sreedhara
    ;
    Sheik Sulthan Alavudeen
    ;
    Patankar Suresh
    ;
    Arumugam Venkatesh
    ;
    Radha Venkatramanan
    ;
    Visweswar Reddy
    ;
    Kundan Wadhai
    ;
    Wen J. Liu
    ;
    Azrini Abdul Aziz
    ;
    Zulhijah Abdul Aziz
    ;
    Mohamad Zaimi bin Abdul Wahab
    ;
    Mohd Kamil Ahmad
    ;
    Nuzaimin Hadafi Ahmad
    ;
    Norazinizah Ahmad Ahmad Miswan
    ;
    Durga Arinandini Arimuthu
    ;
    Alia Bahtar
    ;
    Sunita Bavanandam
    ;
    Jin Kiang Cheng
    ;
    Mei Chih Cheng
    ;
    Yong Fatt Cheng
    ;
    Jing Ling Choe
    ;
    LIK WEE EE
    ;
    Mei Sian Fu
    ;
    Karin Lam
    ;
    Soon Leng Lee
    ;
    Yee Wan Lee
    ;
    Yewfong Liew
    ;
    Sadanah Aqashiah Bt Mazlan
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    Fariz Safhan Mohamad Nor
    ;
    Mohd Ramadhan bin Mohd Din
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    Ili Najihah Muhammad Amin
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    Ashwani Murugiah
    ;
    Lily Mushahar
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    Nabia Idaam Mustapa Albakari
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    M. Nadesan
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    Megaleswary Narthan
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    Nurul Zaynah Nordin
    ;
    Yusof Nurul Ain
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    Yu Chen Ong
    ;
    Rafizanur Ramli
    ;
    Shahnaz Shah Firdaus Khan
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    Hafiz Aizat Bin Shuhaimi
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    Goh Chung Siew
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    Min Hui Tan
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    Kok Seng Teng
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    Asiah Binti Usamah
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    Wan Ahmad Hafiz Wan Md Adnan
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    Wan Hazlina Wan Mohamad
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    Irene Wong
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    Rosnawati Yahya
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    Seow Yeing Yee
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    Harun Zaiha
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    Nur Nadzifah Hanim binti Zainal Abidin
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    Janak R. de Zoysa
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    Hussain Allawati
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    Jayana Devathasan
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    Redzuan Hassan
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    Andrew McNally
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    Adam Mullan
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    Norman Panlilio
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    Tracey Putt
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    Kannaiyan Rabindranath
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    Sabrina Sapsford
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    Robert Walker
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    Mustafa Arici
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    Bilal Görçin
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    Patrick B. Mark
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    Allifia Abbas
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    Bamidele Ajayi
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    Jennifer Allen
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    Charlotte Bebb
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    Samira Bell
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    Linda Bisset
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    Kate Bramham
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    James Burton
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    Rajkumar Chinnadurai
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    Chukwuma Chukwu
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    Laura Clark
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    Thomas Connor
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    Indranil Dasgupta
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    Tanaji Dasgupta
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    Timothy Doulton
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    Christopher Farmer
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    Charles Ferro
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    Anna Forbes
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    Chris Goldsmith
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    Judi Graham
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    Awais Hameed
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    Christopher Hill
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    Neil Hoye
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    Farhana Ibrahim Lutfi
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    Mark Jesky
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    Asra Karim
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    Declan Keenan
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    Mark Lambie
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    Niall Leonard
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    Ming Leung
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    Kateryna MacConaill
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    Agnes Masengu
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    Kieran McCafferty
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    Richard McCrory
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    Emily McQuarrie
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    Anjali Menon
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    Shona Methven
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    Sayra Mohir
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    Neal Morgan
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    Tharindra Navodhi Somasinghe
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    Bhavna Pandya
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    Panoraia Papadopoulou
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    Rajan Patel
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    Khai Ping Ng
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    Albert Power
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    Rhodri Pyart
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    Ashveer Randhay
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    Anirudh Rao
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    Nick Selby
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    Edward Sharples
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    Tim Shipley
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    Priscilla Smith
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    John Smyth
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    Joshua Storrar
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    Sokratis Stoumpos
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    Michael Sullivan
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    Pauline Swift
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    Beatrix Tan
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    Peihwa Thing
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    Mona Wahba
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    Alastair Woodman
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    Laura Sola
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    Cecilia Baccino
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    Juan Carlos Diaz
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    Susana Gonzalez
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    Rodrico Menoni
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    David Miller
    Background: Patients undergoing maintenance dialysis for kidney failure are at substantial risk of cardiovascular morbidity and mortality. We aimed to establish if spironolactone reduces heart failure and cardiovascular deaths in these patients. Methods: ACHIEVE was an international, parallel-group, randomised controlled trial done in 143 dialysis programmes in 12 countries. Patients were aged 45 years or older, or aged 18 years or older with a history of diabetes, and were receiving maintenance dialysis for kidney failure for at least 3 months at the time of recruitment. Patients who were able to tolerate and adhere to spironolactone 25 mg daily orally during an open-label run-in were randomly assigned (1:1) to continue spironolactone or matching placebo, using a central computerised block randomisation system (block sizes of 4) stratified by centre. Participants, health-care providers, and those assessing outcomes were masked to group assignment. The primary outcome was a composite of cardiovascular mortality or hospitalisation for heart failure analysed as time-to-event in all randomly assigned participants. The trial was registered at ClinicalTrials.gov, NCT03020303. Findings: After a planned interim analysis of 75% of the expected primary outcome events, the external safety and efficacy monitoring committee recommended the trial be stopped early for futility. From Sept 19, 2017, to Oct 31, 2024, 3689 patients were screened for inclusion, 3565 of whom were enrolled in the open-label run-in phase, and 2538 were randomly assigned to spironolactone (n=1260) or placebo (n=1278). 931 (36·7%) participants were female and 1607 (63·3%) were male. Median follow-up was 1·8 years (IQR 0·85–3·35). The composite primary outcome occurred in 258 participants (10·46 events per 100 patient-years) in the spironolactone group and in 276 participants (11·33 per 100 patient-years) in the placebo group (hazard ratio [HR] 0·92 [95% CI 0·78–1·09]; p=0·35). Death from any cause was similar between groups (HR 0·95 [0·83–1·09]) as was hospitalisation for any cause (HR 0·96 [0·87–1·06]). Interpretation: Among patients receiving maintenance dialysis, spironolactone 25 mg daily orally did not reduce the composite outcome of cardiovascular mortality and hospitalisation due to heart failure compared with placebo. This trial did not identify a benefit of initiating spironolactone in patients receiving maintenance dialysis. Future research should consider alternatives to steroidal mineralocorticoid receptor antagonism to reduce cardiovascular morbidity and mortality in patients receiving maintenance haemodialysis. Funding: The Canadian Institutes of Health Research, The Medical Research Future Fund, The Health Research Council, The British Heart Foundation, Population Health Research Institute/Hamilton Health Sciences Research Institute, St Joseph's Healthcare Hamilton Division of Nephrology, Accelerating Clinical Trials Consortium, Can-SOLVE CKD Network, and the Dalhousie Department of Medicine.

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