Spironolactone to increase natriuresis in congestive heart failure with cardiorenal syndrome

Background: Signs and symptoms of volume overload are the most frequent reason for hospital admission in acute heart failure (AHF). Diuretics are mainstay treatment, but their optimal type and dose regimen remain unclear, especially in patients with cardiorenal syndrome. Methods: This prospective study aimed to include 80 AHF patients with volume overload and cardiorenal syndrome. Through a 2 x 2 factorial design, patients were randomised towards (1) combinational treatment with acetazolamide and low-dose loop diuretics versus high-dose loop diuretics; and (2) open-label oral spironolactone 25mg OD given upfront versus at discharge. Here reported are the results of the spironolactone treatment arm after complete follow-up of 34/80 patients (since the study was stopped because of slow recruitment). The primary study end-point was incident hypokalaemia (<3.5mmol/L) or hyperkalaemia (>5.5mmol/L). Results: Serum potassium derangements were numerically less frequent in the upfront versus discharge spironolactone group, yet this result was underpowered due to incomplete study recruitment (hyperkalaemia: 6% vs. 11%; hypokalaemia: 13% vs. 28%, respectively; p-value = .270). Natriuresis after 24 h was higher in the upfront vs. discharge spironolactone group (314 +/- 142 vs. 200 +/- 91mmol/L, respectively; p-value 1/4 .010). Relative change in plasma NT-proBNP level after 72 h was similar among both groups (-16 +/- 29% vs. -5 +/- 45%, respectively; p value = .393), with no difference in all-cause mortality (p-value 1/4 .682) or the combination of all-cause mortality and heart failure readmission (p-value = .799). Discussion: Spironolactone use upfront in AHF patients at high risk for cardiorenal syndrome is safe and increases natriuresis.