Publications
Spironolactone versus placebo in patients undergoing maintenance dialysis (ACHIEVE): an international, parallel-group, randomised controlled trial.
Michael Walsh, MD PhDa,b mwwalsh@mcmaster.ca ∙ David Collister, MD PhDa,c ∙ Martin Gallagher, MBChB PhDd,e ∙ Patrick B Mark, MBChB PhDf ∙ Janak R de Zoysa, MBChB MClinEdg,h ∙ Jessica Tyrwhitt, BSca ∙ Karthik Tennankore, MD MSci,j ∙ Gilmar Reis, MD PhDb,k ∙ Denis Xavier, MD PhDl ∙ Wen J Liu, MBChBm ∙ Li Zuo, MD PhDn ∙ Amanda Y Wang, MD PhDe,o,p ∙ Camilo Félix, MD PhDq ∙ Laura Sola, MDr ∙ Mustafa Arici, MD PhDs ∙ Russell Villanueva, MDt ∙ Vivekanand Jha, MD PhDu,v,w ∙ Dalton Précoma, MD PhDx ∙ Christian G Rabbat, MD MScb ∙ Sheik Sulthan Alavudeen, MDy ∙ Atiya R Faruqui, MD 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]).
