Spironolactone versus placebo in patients undergoing maintenance dialysis - ACHIEVE: an international, parallel-group, randomised controlled trial
Journal
The Lancet
ISSN
0140-6736
Date Issued
2025-08
Author(s)
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
Laura Sola
Mustafa Arici
Russell Villanueva
Vivekanand Jha
Dalton Précoma
Christian G Rabbat
Sheik Sulthan Alavudeen
Atiya R Faruqui
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
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
Akshaya R. Faruqui
Freeda Xavier
Preeti Girish
Remya Giriraju
Susan Subbin
Jagannath Rao
Mary Baker
Lyndel Rive
Lynsey Gillespie
Emma Moody
Shannon Fairley
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
Fariz Safhan Mohamad Nor
Mohd Ramadhan bin Mohd Din
Ili Najihah Muhammad Amin
Ashwani Murugiah
Lily Mushahar
Nabia Idaam Mustapa Albakari
M. Nadesan
Megaleswary Narthan
Nurul Zaynah Nordin
Yusof Nurul Ain
Yu Chen Ong
Rafizanur Ramli
Shahnaz Shah Firdaus Khan
Hafiz Aizat Bin Shuhaimi
Goh Chung Siew
Min Hui Tan
Kok Seng Teng
Asiah Binti Usamah
Wan Ahmad Hafiz Wan Md Adnan
Wan Hazlina Wan Mohamad
Irene Wong
Rosnawati Yahya
Seow Yeing Yee
Harun Zaiha
Nur Nadzifah Hanim binti Zainal Abidin
Janak R. de Zoysa
Hussain Allawati
Jayana Devathasan
Redzuan Hassan
Andrew McNally
Adam Mullan
Joanne O' Riordan
Norman Panlilio
Tracey Putt
Kannaiyan Rabindranath
Sabrina Sapsford
Robert Walker
Russell Villanueva
Ray Tan
Mustafa Arici
Bilal Görçin
Sultan Güvenir Özkurt
Guldehan Haberal
Tugce Olgac Sarikulak
Rukiye Tektaş
Patrick B. Mark
Allifia Abbas
Bamidele Ajayi
Jennifer Allen
Charlotte Bebb
Samira Bell
Linda Bisset
Kate Bramham
James Burton
Rajkumar Chinnadurai
Chukwuma Chukwu
Laura Clark
Thomas Connor
Indranil Dasgupta
Tanaji Dasgupta
Timothy Doulton
Christopher Farmer
Charles Ferro
Anna Forbes
Chris Goldsmith
Judi Graham
Awais Hameed
Christopher Hill
Neil Hoye
Farhana Ibrahim Lutfi
Mark Jesky
Asra Karim
Declan Keenan
Mark Lambie
Niall Leonard
Ming Leung
Kateryna MacConaill
Agnes Masengu
Kieran McCafferty
Richard McCrory
Emily McQuarrie
Anjali Menon
Shona Methven
Sayra Mohir
Neal Morgan
Tharindra Navodhi Somasinghe
Bhavna Pandya
Panoraia Papadopoulou
Rajan Patel
Khai Ping Ng
Albert Power
Rhodri Pyart
Ashveer Randhay
Anirudh Rao
Nick Selby
Edward Sharples
Tim Shipley
Priscilla Smith
John Smyth
Joshua Storrar
Sokratis Stoumpos
Michael Sullivan
Pauline Swift
Beatrix Tan
Peihwa Thing
Mona Wahba
Alastair Woodman
Laura Sola
Cecilia Baccino
Juan Carlos Diaz
Susana Gonzalez
Rodrico Menoni
David Miller
Abstract
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.
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.