Guideline-recommended IV loop diuretics improve symptoms of fluid overload in patients with acute decompensated heart failure (HF), but many have residual congestion. While sequential diuretics may provide an answer,1,2 decisive evidence on the optimal drugs, dosing schedule and route of administration is lacking.
In a Hot Line session yesterday, Professor Wilfried Mullens (Hospital Oost-Limburg [ZOL] - Genk, Belgium) presented results from the largest diuretic trial performed in patients with acute decompensated HF, the ADVOR trial, which investigated whether adding the carbonic anhydrase inhibitor, acetazolamide, to IV loop diuretics would improve decongestion and outcomes.
Participants in this randomised, double-blind, pragmatic investigator-initiated trial were hospitalised with acute HF, had clinically evident volume overload and elevated NT-proBNP, and had received at least 1 month of maintenance therapy with loop diuretics. Participants were randomised 1:1 to receive IV acetazolamide (500 mg once daily, administered as a bolus upon randomisation and during the next 2 days or until successful decongestion) or placebo, stratified according to ejection fraction (<40% versus ≥40%). At randomisation, oral loop diuretics were stopped and all patients received high-dose IV loop diuretics. The primary endpoint was successful decongestion, defined as no clinical signs of fluid overload (other than trace oedema) within 3 days of randomisation without the need for escalation of decongestive therapy.
A total of 519 adults with an average age of 78 years (63% male) were enrolled at 27 centres in Belgium.
The primary endpoint of successful decongestion was more frequent in patients receiving acetazolamide compared with placebo (42.2% versus 30.5%; relative risk [RR] 1.46; 95% CI 1.17 to 1.82; p=0.0009).
Among 473 patients alive at discharge, successful decongestion was achieved in 78.8% receiving acetazolamide and 62.5% receiving placebo (RR 1.27; 95% CI 1.13 to 1.43; p=0.0001). In terms of secondary endpoints, acetazolamide was associated with a shorter hospital stay than placebo (average 8.8 days versus 9.9 days, respectively; p=0.02) but there was no difference between groups in the composite outcome of all-cause mortality and hospitalisation for HF within 3 months.
Discussing the results, Prof. Mullens says: “Patients treated with acetazolamide had more diuresis and natriuresis, and were more likely to be discharged without residual signs of volume overload. There did not appear to be an increase in adverse events with the drug. Participants had similar characteristics to patients in real-world practice, including a high degree of congestion, advanced age and many comorbidities.” He concludes: “Acetazolamide is easy to use, safe, effective, off-patent and cheap. It is therefore expected that the results of ADVOR will lead to a paradigm shift in the way physicians worldwide treat acute decompensated HF.”