Cardiol Res

Cardiology Research, ISSN 1923-2829 print, 1923-2837 online, Open Access

Article copyright, the authors; Journal compilation copyright, Cardiol Res and Elmer Press Inc

Journal website https://www.cardiologyres.org

Review

Volume 15, Number 2, April 2024, pages 69-74

Acetazolamide and Hydrochlorothiazide in Patients With Acute Decompensated Heart Failure: Insights From Recent Trials

**Table 1.** Summary of Studies Included in the Review
Authors	Mullens et al 2022 [11] (ADVOR trial)	Kosiorek et al 2023 [12]	Trullas et al 2023 [13] (CLOROTIC trial)	Piardi et al 2021 [14]
^aYear of publication. ^bLocationc of study. ^cReported all-cause rehospitalization. GFR: glomerular filtration rate; EF: ejection fraction; HF: heart failure; NA: not available; NS: no significant difference between groups.
Year^a	2022	2023	2023	2021
Patients number	519	61	230	51
Location^b	Belgium	Poland	Spain	Brazil
Enrollment timing (of hospital admission)	Within 24 h	Within 24 h	Within 24 h	Within 24 h
Start time for therapy (of hospital admission)	Day 1	Day 1	Day 1	Day 1
Randomized therapy	Placebo vs. IV acetazolamide 500 mg daily for 3 days (double-blind)	Acetazolamide 250 mg orally daily for 2 days vs. standard care (single-blind)	Hydrochlorothiazide based on patient’s GFR: > 50 mL/min: 25 mg daily; 20 - 50 mL/min: 50 mg daily; and < 20 mL/min: 100 mg daily	Hydrochlorothiazide 50 mg
Background therapy	IV loop diuretic	IV furosemide	IV furosemide	IV furosemide
Baseline EF in intervention group	43 ± 15	36 ± 15	55 (40 - 63)	30 ± 8
Baseline renal function	GFR: 39 mL/min	GFR: 58 mL/min	GFR: 43 mL/min	GFR: 30 mL/min
Dyspnea	NA	NS	NS	NS
Diuresis in 48 h	4,689 vs. 4,166 mL at day 2	5,300 vs. 3,750 mL at 48 h	1,775 vs. 1,400 mL at 24 h	NA
Natriuresis	91 vs. 80 mmol/L on day 2	114.7 vs. 74.4 mmol/L on day 2	Higher in the thiazide group at 96 h	NA
Fluid balance	NA	-1,232 mL vs. -597 mL on day 2	NA	NA
Weight loss	NA	3.2 kg vs. 1.13 kg at day 2	2.3 kg vs. 1.5 kg after 72 h	1.78 kg vs. 1.05 kg/day
Length of hospital stay	NS	NA	NS	NS
Worsening renal function	NS	NS	Higher in the thiazide group	NS
Hypokalemia (≤ 3.0 mmol/L)	NS	NS	Higher in the thiazide group	NS
Hypotension	NS	NA	NS	NA
HF rehospitalization within 3 months	NS	NA	NS^c	NA
Death from any cause within 3 months	NS	NA	NS	NA
Key finding	Successful decongestion in 42.2% vs. 30.5%	The acetazolamide group had significantly higher diuresis, negative fluid balance, and weight loss.	Adding oral hydrochlorothiazide to IV furosemide improves diuretic response in acute decompensated HF patients but has an increased risk of worsening renal function.	Adding hydrochlorothiazide 50 mg to usual treatment resulted in a synergistic effect on weight loss, with a statistically significant increase in the diuretic effect for every 40 mg of IV furosemide used in patients with acute decompensated HF

Table 1. Summary of Studies Included in the Review

Authors

Mullens et al 2022 [11] (ADVOR trial)

Kosiorek et al 2023 [12]

Trullas et al 2023 [13] (CLOROTIC trial)

Piardi et al 2021 [14]

^aYear of publication. ^bLocationc of study. ^cReported all-cause rehospitalization. GFR: glomerular filtration rate; EF: ejection fraction; HF: heart failure; NA: not available; NS: no significant difference between groups.

Year^a

2022

2023

2021

Patients number

519

230

Location^b

Belgium

Poland

Spain

Brazil

Enrollment timing (of hospital admission)

Within 24 h

Start time for therapy (of hospital admission)

Day 1

Randomized therapy

Placebo vs. IV acetazolamide 500 mg daily for 3 days (double-blind)

Acetazolamide 250 mg orally daily for 2 days vs. standard care (single-blind)

Hydrochlorothiazide based on patient’s GFR: > 50 mL/min: 25 mg daily; 20 - 50 mL/min: 50 mg daily; and < 20 mL/min: 100 mg daily

Hydrochlorothiazide 50 mg

Background therapy

IV loop diuretic

IV furosemide

Baseline EF in intervention group

43 ± 15

36 ± 15

55 (40 - 63)

30 ± 8

Baseline renal function

GFR: 39 mL/min

GFR: 58 mL/min

GFR: 43 mL/min

GFR: 30 mL/min

Dyspnea

Diuresis in 48 h

4,689 vs. 4,166 mL at day 2

5,300 vs. 3,750 mL at 48 h

1,775 vs. 1,400 mL at 24 h

Natriuresis

91 vs. 80 mmol/L on day 2

114.7 vs. 74.4 mmol/L on day 2

Higher in the thiazide group at 96 h

Fluid balance

-1,232 mL vs. -597 mL on day 2

Weight loss

3.2 kg vs. 1.13 kg at day 2

2.3 kg vs. 1.5 kg after 72 h

1.78 kg vs. 1.05 kg/day

Length of hospital stay

Worsening renal function

Higher in the thiazide group

Hypokalemia (≤ 3.0 mmol/L)

Higher in the thiazide group

Hypotension

HF rehospitalization within 3 months

NS^c

Death from any cause within 3 months

Key finding

Successful decongestion in 42.2% vs. 30.5%

The acetazolamide group had significantly higher diuresis, negative fluid balance, and weight loss.

Adding oral hydrochlorothiazide to IV furosemide improves diuretic response in acute decompensated HF patients but has an increased risk of worsening renal function.

Adding hydrochlorothiazide 50 mg to usual treatment resulted in a synergistic effect on weight loss, with a statistically significant increase in the diuretic effect for every 40 mg of IV furosemide used in patients with acute decompensated HF