Effectiveness of Natriuresis-Guided Diuretic Therapy in Patients With Acute Heart Failure
abstract
This abstract is available on the publisher's site.
Access this abstract nowMeasurement of natriuresis has been suggested as a reliable, easily obtainable biomarker for assessment of the response to diuretic treatment in patients with acute heart failure (AHF). Here, to assess whether natriuresis-guided diuretic therapy in patients with AHF improves natriuresis and clinical outcomes, we conducted the pragmatic, open-label Pragmatic Urinary Sodium-based algoritHm in Acute Heart Failure trial, in which 310 patients (45% female) with AHF requiring treatment with intravenous loop diuretics were randomly assigned to natriuresis-guided therapy or standard of care (SOC). In the natriuresis-guided arm, natriuresis was determined at set timepoints, prompting treatment intensification if spot urinary sodium levels were <70 mmol l-1. The dual primary endpoints were 24 h urinary sodium excretion and a combined endpoint of time to all-cause mortality or adjudicated heart failure rehospitalization at 180 days. The first primary endpoint was met, as natriuresis in the natriuresis-guided and SOC arms was 409 ± 178 mmol arm versus 345 ± 202 mmol, respectively (P = 0.0061). However, there were no significant differences between the two arms for the combined endpoint of time to all-cause mortality or first heart failure rehospitalization, which occurred in 46 (31%) and 50 (31%) of patients in the natriuresis-guided and SOC arms, respectively (hazard ratio 0.92 [95% confidence interval 0.62-1.38], P = 0.6980). These findings suggest that natriuresis-guided therapy could be a first step towards personalized treatment of AHF. ClinicalTrials.gov registration: NCT04606927 .
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Natriuresis-guided diuretic therapy in acute heart failure: a pragmatic randomized trial
Nat. Med. 2023 Aug 28;[EPub Ahead of Print], JM Ter Maaten, IE Beldhuis, P van der Meer, JA Krikken, D Postmus, JE Coster, W Nieuwland, DJ van Veldhuisen, AA Voors, K DammanFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
Decompensated heart failure remains one of the most common causes of hospital admission. Decongestion is a key component in the treatment of these patients, but evidence-based approaches to achieve decongestion or evaluate for diuretic response are limited. Historically, changes in weight and/or net fluid output have been used as surrogates to diuretic response despite frequent inaccuracies and difficulty in clinical practice.1,2 In contrast, a more objective and inexpensive marker of diuretic response, spot urinary sodium levels, has been shown to improve decongestion.3 However, randomized data assessing such an approach are limited.
The Pragmatic Urinary Sodium-based algoritHm in Acute Heart Failure randomized clinical trial evaluated a natriuresis-guided arm (protocolized escalation in diuretics for urinary sodium levels <70 mmol l-1 and/or urinary output <150 ml h-1) compared with standard of care driven by the discretion of the treating physician.4 Not surprisingly, the natriuresis-guided arm resulted in increased urinary natriuresis (P = .0061), but clinical outcomes, including 180-day all-cause mortality, length of hospital stay, and heart failure rehospitalization, were not different between groups. Notably, safety outcomes such as renal injury were not different between groups despite significantly more diuretic administration in the natriuresis-guided arm.
Ultimately, this study found that a protocolized diuretic approach driven by objective data (urinary sodium levels and/or urine output) resulted in greater natriuresis. Whether outcomes would have differed if the standard-of-care arm was also protocolized and driven by another objective measure, such as urinary output, remained unclear. However, it is reasonable and likely useful to check spot urinary sodium levels to guide your diuretic management, assuming your institution is equipped to quickly release these results. If not, the current evidence base suggests that a natriuretic approach improves natriuresis, but whether this additional test improves outcomes is not supported. Diuretic management requires an active approach, whether that is frequently assessing urine output or spot urine sodium, so that escalation in diuretics is not delayed.
References
Ter Maaten JM, Beldhuis IE, van der Meer P, et al. Natriuresis-guided diuretic therapy in acute heart failure: a pragmatic randomized trial. Nat Med. 2023. Aug 28. doi: 10.1038/s41591-023-02532-z. Online ahead of print. https://www.nature.com/articles/s41591-023-02532-z