Add on Acetazolamide to loop diuretics accelerated decongestion in HF patients: NEJM

Belgium: Acetazolamide added to loop diuretic treatment resulted in a higher rate of effective decongestion in patients with acute decompensated heart failure, says an article published in The New England Journal of Medicine.

It is uncertain if acetazolamide, a carbonic anhydrase inhibitor that lowers proximal tubular sodium reabsorption, might increase loop diuretic efficiency, perhaps leading to greater and faster decongestion in patients with acute decompensated heart failure with volume overload. As a result, Wilfried Mullens and colleagues undertook this research to assess the efficacy of acetazolamide in heart failure.

In this multicenter, randomized trial, researchers randomly assigned a total of 519 patients suffering from acute decompensated heart failure, clinical signs of volume overload (pleural effusion, edema, or ascites), and an N-terminal pro-B-type natriuretic peptide level of more than 1000 pg per milliliter or a B-type natriuretic peptide level of more than 250 pg per mill (at a dose equivalent to twice the oral maintenance dose). The randomization was stratified based on the left ventricular ejection fraction (40% or above). The primary end goal was effective decongestion, defined as the absence of symptoms of volume overload three days following randomization and without the need for decongestive treatment escalation.

The key findings of this study were:

1. 108 of 256 patients (42.2%) in the acetazolamide group and 79 of 259 (30.5%) in the placebo group experienced successful decongestion (risk ratio, 1.46).

2. 76 of 256 patients (29.7%) in the acetazolamide group and 72 of 259 patients (27.8%) in the placebo group had death from any cause or rehospitalization for heart failure (hazard ratio, 1.07).

3. Higher cumulative urine production and natriuresis were linked to acetazolamide therapy, suggesting improved diuretic efficacy.

4. Similar rates of adverse events, hypokalemia, deteriorating renal function, and hypotension were seen in the two groups.

Reference: 

Mullens, W., Dauw, J., Martens, P., Verbrugge, F. H., Nijst, P., Meekers, E., Tartaglia, K., Chenot, F., Moubayed, S., Dierckx, R., Blouard, P., Troisfontaines, P., Derthoo, D., Lassus, J., … Dupont, M. (2022). Acetazolamide in Acute Decompensated Heart Failure with Volume Overload. In New England Journal of Medicine (Vol. 387, Issue 13, pp. 1185–1195). Massachusetts Medical Society. https://doi.org/10.1056/nejmoa2203094