Combination diuretic therapy for acute heart failure: ‘alone we can do so little; together we can do so much’

Abstract

This article refers to 'Acetazolamide in Decompensated Heart Failure with Volume Overload trial (ADVOR): baseline characteristics' by W. Mullens et al., published in this issue on pages 1601-1610.Acute heart failure (AHF) is associated with high in-hospital and post-discharge 1-year mortality, with rates up to 9% and 31%, respectively. 1,2 Evidence-based treatments for AHF are limited. So far, intravenous loop diuretics have one of the strongest (class I) recommendations for its treatment. 3 They are effective at reducing the signs and/or symptoms of volume overload and are recommended therapies across the entire spectrum of left ventricular ejection fraction. 3 However, the level of evidence is C, given the lack of large randomized controlled trials (RCTs) investigating the prognostic benefit of diuretic therapy compared to placebo. Their effects on mortality can only be extrapolated from small RCTs or meta-analyses. However, many of these studies did not specifically investigate patients with AHF, and used evidence being derived from trials using surrogate endpoints. 4 In addition, large RCTs of prognostic therapy for heart failure with reduced ejection fraction (HFrEF) recruited patients with high background rates of loop diuretic prescription, which adds indirect evidence for their use alongside guideline-directed therapy.Sequential nephron blockade is used as a second-line regimen to treat diuretic resistance, defined as an impaired sensitivity to diuretics resulting in reduced natriuresis and diuresis, and persistent congestion. 3,5 However, few studies have specifically examined combination therapy (Figure 1). In this issue of the Journal, Mullens et al. 6 describe the baseline characteristics of patients enrolled to the Acetazolamide in Decompensated Heart Failure with Volume Overload (ADVOR) trial and compare these to other contemporary trials in AHF. ADVOR is a multicentre, randomized, double-blind, placebo-controlled trial of acetazolamide in combination with intravenous loop diuretic therapy in admitted patientsThe opinions expressed in this article are not necessarily those of the Editors of the European Journal of Heart Failure or of the European Society of Cardiology.

Diuretic Treatment in Patients with Heart Failure: Current Evidence and Future Directions—Part II: Combination Therapy

“…However, most patients admitted with severe congestion spend more than a week in hospital [ 14 ]. Early use of combination therapy may lead to rapid decongestion, [ 15 ] which may shorten hospital stay, reducing the risk of nosocomial infection, falls, and physical deconditioning. This, in turn, may lead to improved quality of life (QoL) and better outcomes [ 16 ].…”