P1235THE IMPACT OF SPIRONOLACTONE ON DIASTOLIC FUNCTION IN HEMODIALYSIS PATIENTS - THE MIRENDA RCT

Abstract Background and Aims Patients on maintenance hemodialysis (HD) treatment are particularly prone to develop cardiovascular disease. Heart failure with preserved ejection fraction (HFpEF) characterized by diastolic dysfunction (DD) is highly prevalent and lacks an effective treatment to date. We investigated the effect of the mineralocorticoid receptor antagonist spironolactone compared to placebo on diastolic function in maintenance HD patients. Method The MiREnDa trial was a multicenter randomized-controlled trial that recruited 97 HD patients without previous spironolactone treatment. Participants were randomized 1:1 to spironolactone 50 mg once daily (n=50) or placebo (n=47). Changes in parameters of diastolic function were secondary endpoints of the trial whereas the primary endpoint was change in left ventricular mass index (LVMi). At baseline and after 40 weeks, subjects underwent echocardiography and biomarker testing. DD was defined according to the American Society of Echocardiography 2016 guidelines. Results At baseline, mean age was 58.3 ± 13.0 years, 13 subjects were female and 28 presented with NYHA grade II or higher. Median serum level of NT-proBNP was 2,803 (quartiles: 1,060; 10,676) pg/ml, median previous time on dialysis was 45.0 (quartiles: 21.0; 79.0) months. 28 patients (45.9%) had normal diastolic function, 16 (26.2%) were diagnosed with grade 1 DD, 15 (24.6%) with grade 2 DD and 2 (3.3%) with grade 3 DD. In the remaining cases, the grade of DD was rated indeterminate. There were no significant disparities between the placebo and spironolactone group regarding baseline characteristics. At follow-up, diastolic function improved in two and deteriorated in three subjects on spironolactone treatment, whereas in the placebo group, diastolic function improved in three and deteriorated in two patients. No change in diastolic function was observed in 14 individuals on spironolactone treatment and in 10 receiving placebo (Pearson’s Χ: p=0.87). According to the diagnostic algorithm proposed by the American society of Echocardiography 2016 guideline, 18 patients (11 on spironolactone; 7 on placebo) could no longer be allocated to a distinct group of DD. These patients needed to be classified as indeterminate, even though they only showed mild alterations in diastolic function parameters. Conclusion In this randomized, placebo-controlled trial, 40 weeks of spironolactone treatment did not change diastolic function in HD patients.