Please use this identifier to cite or link to this item:
http://hdl.handle.net/1942/40132
Title: | Pre-treatment bicarbonate levels and decongestion by acetazolamide: the ADVOR trial | Authors: | MARTENS, Pieter VERBRUGGE, Frederik DAUW, Jeroen NIJST, Petra MEEKERS, Evelyne Augusto Jr, Silvio Nunes Ter Maaten, Jozine M. HEYLEN, Line Damman, Kevin Mebazaa, Alexandre Filippatos, Gerasimos Ruschitzka, Frank Tang, Wai Hong Wilson DUPONT, Matthias MULLENS, Wilfried |
Issue Date: | 2023 | Publisher: | OXFORD UNIV PRESS | Source: | EUROPEAN HEART JOURNAL, | Status: | Early view | Abstract: | Aims Acetazolamide inhibits proximal tubular sodium and bicarbonate re-absorption and improved decongestive response in acute heart failure in the ADVOR trial. It is unknown whether bicarbonate levels alter the decongestive response to acetazolamide. Methods and results This is a sub-analysis of the randomized, double-blind, placebo-controlled ADVOR trial that randomized 519 patients with acute heart failure and volume overload in a 1:1 ratio to intravenous acetazolamide (500 mg/day) or matching placebo on top of standardized intravenous loop diuretics (dose equivalent of twice oral maintenance dose). The primary endpoint was complete decongestion after 3 days of treatment (morning of day 4). Impact of baseline HCO3 levels on the treatment effect of acetazolamide was assessed. : Of the 519 enrolled patients, 516 (99.4%) had a baseline HCO3 measurement. Continuous HCO3 modelling illustrated a higher proportional treatment effect for acetazolamide if baseline HCO3 >= 27 mmol/l. A total of 234 (45%) had a baseline HCO3 >= 27 mmol/l. Randomization towards acetazolamide improved decongestive response over the entire range of baseline HCO3- levels (P = 0.004); however, patients with elevated baseline HCO3 exhibited a significant higher response to acetazolamide [primary endpoint: no vs. elevated HCO3; OR 1.37 (0.79-2.37) vs. OR 2.39 (1.35-4.22), P-interaction = 0.065), with higher proportional diuretic and natriuretic response (both P-interaction < 0.001), greater reduction in congestion score on consecutive days (treatment x time by HCO3-interaction <0.001) and length of stay (P-interaction = 0.019). The larger proportional treatment effect was mainly explained by the development of diminished decongestive response in the placebo arm (loop diuretics only), both with regard to reaching the primary endpoint of decongestion as well as reduction in congestion score. Development of elevated HCO3 further worsened decongestive response in the placebo arm (P-interaction = 0.041). A loop diuretic only strategy was associated with an increase in the HCO3 during the treatment phase which was prevented by acetazolamide (day 3: placebo 74.8% vs. acetazolamide 41.3%, P < 0.001). Conclusion Acetazolamide improves decongestive response over the entire range of HCO3- levels; however, the treatment response is magnified in patients with baseline or loop diuretic-induced elevated HCO3 (marker of proximal nephron NaHCO3 retention) by specifically counteracting this component of diuretic resistance. | Notes: | Mullens, W (corresponding author), Ziekenhuis Oost Limburg AV, Dept Cardiol, Schiepse bos 6, B-3600 Genk, Belgium. wilfried.mullens@zol.be |
Keywords: | Acute heart failure;Decongestion;Acetazolamide;Diuresis;Natriuresis | Document URI: | http://hdl.handle.net/1942/40132 | ISSN: | 0195-668X | e-ISSN: | 1522-9645 | DOI: | 10.1093/eurheartj/ehad236 | ISI #: | 000979872700001 | Rights: | The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com | Category: | A1 | Type: | Journal Contribution |
Appears in Collections: | Research publications |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
Pre-treatment bicarbonate levels and decongestion by acetazolamide_ the ADVOR trial.pdf Restricted Access | Published version | 895.18 kB | Adobe PDF | View/Open Request a copy |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.