Clinical Question

Does the addition of acetazolamide to intravenous loop diuretics lead to faster decongestion in hospitalized patients with acute decompensated heart failure?

Bottom Line

For patients with chronic heart failure who are hospitalized with acute volume overload, the addition of acetazolamide to intravenous loop diuretics leads to faster decongestion. Nine patients would need to be treated with acetazolamide to have one patient achieve this outcome. The trial was initiated before the use of sodium-glucose cotransporter-2 (SGLT-2) inhibitors for the treatment of heart failure and had a predominantly White population. The results may not be generalizable to all populations. (Level of Evidence = 1b)

Synopsis

The investigators randomized hospitalized adults with acute decompensated heart failure (i.e., one clinical sign of volume overload plus elevated N-terminal pro-brain natriuretic peptide or brain natriuretic peptide) to receive intravenous acetazolamide, 500 mg daily (n = 259), or matching placebo (n = 260) for three days. All patients received standardized intravenous loop diuretic therapy at double the dose of their oral maintenance therapy. Those taking maintenance acetazolamide or SGLT-2 inhibitors were excluded. Trial participants had a mean age of 78 years, two-thirds were men, and 99% were White. Additionally, 87% were classified as New York Heart Association class III or IV. The primary outcome was successful decongestion, defined as the absence of signs of volume overload within three days of randomization without a need for escalation of decongestive therapy. More patients in the acetazolamide group than in the placebo group achieved the primary outcome (42.2% vs. 30.5%; relative risk [RR] = 1.46; 95% CI, 1.17 to 1.82). This was consistent across all subgroups except for a smaller benefit seen in patients receiving a higher dose of maintenance diuretics compared with those receiving a lower dose. The acetazolamide group had a shorter hospital stay (8.8 vs. 9.9 days; RR = 0.89; 95% CI, 0.81 to 0.98) and a higher incidence of successful decongestion at discharge (78.8% vs. 62.5%; RR = 1.27; 95% CI, 1.13 to 1.43). Adverse events were similar in the two groups, and no differences were detected in death or rehospitalization at three months.