Conference Coverage

Big boost in sodium excretion with HF diuretic protocol 



In patients with acute heart failure, a urine sodium-guided diuretic protocol, currently recommended in guidelines from the Heart Failure Association of the European Society of Cardiology (HFA-ESC), led to significant increases in natriuresis and diuresis over 2 days in the prospective ENACT-HF clinical trial.

The guideline protocol was based on a 2019 HFA position paper with expert consensus, but it had not been tested prospectively, Jeroen Dauw, MD, of AZ Sint-Lucas Ghent (Belgium), explained in a presentation at HFA-ESC 2023.

“We had 282 millimoles of sodium excretion after one day, which is an increase of 64%, compared with standard of care,” Dr. Dauw told meeting attendees. “We wanted to power for 15%, so we’re way above it, with a P value of lower than 0.001.”

The effect was consistent across predefined subgroups, he said. “In addition, there’s an even higher benefit in patients with a lower eGFR [estimated glomerular filtration rate] and a higher home dose of loop diuretics, which might signal more diuretic resistance and more benefit of the protocol.”

After 2 days, the investigators saw 52% higher natriuresis and 33% higher diuresis, compared with usual care.

In an interview, Dr. Dauw said, “The protocol is feasible, safe, and very effective. Cardiologists might consider how to implement a similar protocol in their center to improve the care of their acute heart failure patients.”

Twice the oral home dose

The investigators conducted a multicenter, open-label, nonrandomized pragmatic trial at 29 centers in 18 countries globally. “We aimed to recruit 500 to detect a 15% difference in natriuresis,” Dr. Dauw said in his presentation, “but because we were a really low-budget trial, we had to stop after 3 years of recruitment.”

Therefore, 401 patients participated, 254 in the SOC arm and 147 in the protocol arm, because of the sequential nature of the study; that is, patients in the SOC arm of the two-phase study were recruited first.

Patients’ mean age was 70 years, 38% were women, and they all had at least one sign of volume overload. They were on a maintenance daily diuretic dose of 40 mg of furosemide for a month or more, and the NT-proBNP was above 1,000.

In phase 1 of the study, all centers treated 10 consecutive patients according to the local standard of care, at the discretion of the physician. In phase 2, the centers again recruited and treated at least 10 consecutive patients, this time according to the standardized diuretic protocol.

In the protocol phase, patients were treated with twice the oral home dose as an IV bolus. “This meant if, for example, you have 40 mg of furosemide at home, then you receive 80 mg as a first bolus,” Dr. Dauw told attendees. A spot urine sample was taken after 2 hours, and the response was evaluated after 6 hours. A urine sodium above 50 millimoles per liter was considered a good response.

On the second day, patients were reevaluated in the morning using urine output as a measure of diuretic response. If it was above 3 L, then the same bolus was repeated again twice daily, with 6-12 hours between administrations.

As noted, after one day, natriuresis was 174 millimoles in the SOC arm versus 282 millimoles in the protocol group – an increase of 64%. The effect was consistent across subgroups, and those with a lower eGFR and a higher home dose of loop diuretics benefited more.

Furthermore, Dr. Dauw said, there was no interaction on the endpoints with SGLT2 inhibitor use at baseline.

After two days, natriuresis was 52% higher in the protocol group and diuresis was 33% higher.

However, there was no significant difference in weight loss and no difference in the congestion score.

“We did expect to see a difference in weight loss between the study groups, as higher natriuresis and diuresis would normally be associated with higher weight loss in the protocol group,” Dr. Dauw told this news organization. “However, looking back at the study design, weight was collected from the electronic health records and not rigorously collected by study nurses. Previous studies have shown discrepancies between fluid loss and weight loss, so this is an ‘explainable’ finding.”

Participants also had a relatively high congestion score at baseline, with edema above the knee and also some pleural effusion, he told meeting attendees. Therefore, it might take more time to see a change in congestion score in those patients.

The protocol also led to a shorter length of stay – one day less in the hospital – and was very safe on renal endpoints, Dr. Dauw concluded.

A session chair asked why only patients already on diuretics were included in the study, noting that in his clinic, about half of the admissions are de novo.

Dr. Dauw said that patients already taking diuretics chronically would benefit most from the protocol. “If patients are diuretic-naive, they probably will respond well to whatever you do; if you just give a higher dose, they will respond well,” he said. “We expected that the largest benefit would be in patients already taking diuretics because they have a higher chance of not responding well.”

“There also was a big difference in the starting dose,” he added. “In the SOC arm, the baseline dose was about 60 mg, whereas we gave 120 mg, and we could already see a high difference in the effect. So, in those patients, I think the gain is bigger if you follow the protocol.”


Recommended Reading

CardioMEMS boosts QoL, curbs HF hospitalizations: MONITOR-HF
MDedge Cardiology
Trientine reduces NT-proBNP up to 8 weeks in HFrEF: TRACER-HF
MDedge Cardiology
ARNI bests ARB to reduce NT-proBNP in stabilized preserved-EF HF
MDedge Cardiology
Circulatory support for RV failure caused by pulmonary embolism
MDedge Cardiology
FDA approves new drug, sotagliflozin, for heart failure
MDedge Cardiology
FDA OKs Injectafer for iron deficiency anemia in heart failure
MDedge Cardiology
Medicaid patients with heart failure get poor follow-up after hospital discharge
MDedge Cardiology
EHR nudges a bust for boosting guideline-directed meds in acute HF: PROMPT-AHF
MDedge Cardiology
Dapagliflozin matches non–loop diuretic for congestion in AHF: DAPA-RESIST
MDedge Cardiology
First-line or BiV backup? Conduction system pacing for CRT in heart failure
MDedge Cardiology