TY - JOUR
T1 - Low-dose spironolactone and cardiovascular outcomes in moderate stage Chronic Kidney Disease
T2 - a randomised controlled trial
AU - Hobbs, F D Richard
AU - McManus, Richard J
AU - Taylor, Clare J
AU - Jones, Nicholas R.
AU - Rahman, Joy K
AU - Wolstenholme, Jane
AU - Kim , Sungwook
AU - Kwon, Joseph
AU - Jones, Louise
AU - Hirst, Jennifer A
AU - Yu, Ly-Mee
AU - Mort, Sam
PY - 2024/9/30
Y1 - 2024/9/30
N2 - Chronic kidney disease (CKD) is associated with substantial risk of progression to end stage renal disease and vascular events. The non-steroidal mineralocorticoid receptor antagonist (MRA), finerenone, offers cardio-renal protection for people with CKD and diabetes, but there is uncertainty if the steroidal MRA, spironolactone, provides the same protection. In this prospective, randomised, open, blinded endpoint (PROBE) trial we assessed the effectiveness of 25mg spironolactone in addition to usual care or usual care alone for reducing cardiovascular outcomes in stage 3b CKD among an older community cohort (mean age 74.8 years, standard deviation 8.1). We recruited 1,434 adults from English primary care, of whom 1,372 (96%) were included in the primary analysis. The primary outcome was time from randomisation until the first occurrence of; death, hospitalisation for heart disease, stroke, heart failure, transient ischaemic attack or peripheral arterial disease, or first onset of any condition listed not present at baseline. Across three years of follow-up, the primary endpoint occurred in 113/677 participants randomised to spironolactone (16.7%) and 111/695 randomised to usual care (16.0%) with no significant difference between groups (hazard ratio 1.05, 95%CI:0.81-1.37). Two-thirds of participants randomised to spironolactone stopped treatment within six months, predominantly because they met pre-specified safety stop criteria. The most common reason for stopping spironolactone was a decrease in the estimated glomerular filtration rate that met pre-specified stop criteria (n=239, 35.4%), followed by participants being withdrawn due to treatment side-effects (n=128, 18.9%) and hyperkalaemia (n=54, 8.0%). In conclusion, we found that spironolactone was frequently discontinued due to safety concerns, with no evidence that it reduced cardiovascular outcomes in people with stage 3b CKD. Spironolactone should not be used for people with stage 3b CKD without another explicit treatment indication. ClinicalTrials.gov registration: ISRCTN44522369.
AB - Chronic kidney disease (CKD) is associated with substantial risk of progression to end stage renal disease and vascular events. The non-steroidal mineralocorticoid receptor antagonist (MRA), finerenone, offers cardio-renal protection for people with CKD and diabetes, but there is uncertainty if the steroidal MRA, spironolactone, provides the same protection. In this prospective, randomised, open, blinded endpoint (PROBE) trial we assessed the effectiveness of 25mg spironolactone in addition to usual care or usual care alone for reducing cardiovascular outcomes in stage 3b CKD among an older community cohort (mean age 74.8 years, standard deviation 8.1). We recruited 1,434 adults from English primary care, of whom 1,372 (96%) were included in the primary analysis. The primary outcome was time from randomisation until the first occurrence of; death, hospitalisation for heart disease, stroke, heart failure, transient ischaemic attack or peripheral arterial disease, or first onset of any condition listed not present at baseline. Across three years of follow-up, the primary endpoint occurred in 113/677 participants randomised to spironolactone (16.7%) and 111/695 randomised to usual care (16.0%) with no significant difference between groups (hazard ratio 1.05, 95%CI:0.81-1.37). Two-thirds of participants randomised to spironolactone stopped treatment within six months, predominantly because they met pre-specified safety stop criteria. The most common reason for stopping spironolactone was a decrease in the estimated glomerular filtration rate that met pre-specified stop criteria (n=239, 35.4%), followed by participants being withdrawn due to treatment side-effects (n=128, 18.9%) and hyperkalaemia (n=54, 8.0%). In conclusion, we found that spironolactone was frequently discontinued due to safety concerns, with no evidence that it reduced cardiovascular outcomes in people with stage 3b CKD. Spironolactone should not be used for people with stage 3b CKD without another explicit treatment indication. ClinicalTrials.gov registration: ISRCTN44522369.
U2 - 10.1038/s41591-024-03263-5
DO - 10.1038/s41591-024-03263-5
M3 - Article
SN - 1078-8956
JO - Nature Medicine
JF - Nature Medicine
ER -
