BARACK-D: low-dose spironolactone and cardiovascular outcomes in moderate CKD
People with chronic kidney disease (CKD) are at increased risk of mortality and morbidity through cardiovascular (CV) events and progression to end-stage kidney disease. As the early stages of CKD (stages 1–3) are the most prevalent, in public health terms, this is where the burden of CV risk lies.
Recent studies have demonstrated that finerenone, a non-steroidal mineralocorticoid receptor antagonist (MRA), offers cardiorenal protection for people with CKD and diabetes. It has not been established, however, if the steroidal MRA, spironolactone, provides the same beneficial effects.
BARACK-D (Benefits of Aldosterone Receptor Antagonism in CKD), a prospective, randomised, open, blinded endpoint trial, evaluated the effectiveness of 25 mg spironolactone plus usual care versus usual care alone for reducing CV outcomes in stage 3b CKD. It recruited 1434 adults (mean age at randomisation, 74.8 years; 54.5% women) from primary care in England, of whom 1372 were included in the analyses.
There was a high burden of comorbid CVD among the participants, including hypertension (76.7%), type 2 diabetes (24.3%), ischaemic heart disease (17.4%) and atrial fibrillation (12.2%). Mean eGFR at baseline was 43.5 mL/min/1.73 m2 and ACR 1.5 mg/mmol. The majority were taking either an ACEi (40.0%) or an ARB (36.6%).
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. During 3 years of follow-up, the primary outcome occurred in 113 of 677 participants randomised to spironolactone (16.7%) and 111 of 695 randomised to usual care (16.0%), with no significant difference between groups (HR, 1.05 [95% CI, 0.81–1.37; P=0.702]).
In total, two thirds of participants in the spironolactone group stopped treatment within 6 months, predominantly because of safety concerns. The most common reason (n=239; 35.4%) was a decrease in eGFR that met the prespecified stop criteria, followed by withdrawal owing to treatment side effects (n=128; 18.9%) and hyperkalaemia (n=54; 8.0%).
Although difficulties in recruiting left the study underpowered, the investigators concluded that low-dose spironolactone did not reduce CV outcomes in people with stage 3b CKD. Spironolactone was poorly tolerated and should not be used in this population without another explicit treatment indication.
The full article can be read here.
