Standardised diuretic protocol significantly increases natriuresis in acute HF

A natriuresis-guided protocol in diuretic use compared with standard-of-care led to a significant increase in natriuresis after 24 hours. The benefit of this approach was particularly evident in patients with a lower glomerular filtration rate.

Current guidelines of the European Society of Cardiology (ESC) recommend a natriuresis-guided diuretic use in acute heart failure (HF) following a position statement from the HFA [1,2]. To test whether a standardised diuretic protocol is superior to standard-of-care, Dr Jeroen Dauw (AZ Sint-Lucas, Belgium) and colleagues performed the prospective, multicentre, open-label, non-randomised, pragmatic ENACT-HF trial [3]. The study included 29 centres in 18 countries worldwide. In each centre, standard-of-care was compared with a standardised diuretic protocol in 2 sequential phases of recruitment: standard-of-care was used in phase 1, and the standardised protocol was followed in phase 2.

All 401 study participants had been admitted with acute HF and had at least 1 sign of volume overload. The primary endpoint was natriuresis after 1 day. Secondary endpoints included natriuresis and diuresis after 2 days, weight loss after 2 days, change in a congestion score, and duration of hospitalisation.

Following the standardised protocol led to an increase in natriuresis of 64% after 1 day (natriuresis after 1 day was 174 mmol in the standard-of-care group compared with 282 mmol in the protocol group; 95% CI 1.37–1.95; P<0.001; see Figure). A predefined subgroup analysis revealed that these results remained true independent of age, sex, kidney function, and left ventricular ejection fraction. “Those with a lower glomerular filtration rate had an even higher benefit,” Dr Dauw said.

Figure: A standardised diuretic protocol led to a 64% increase in natriuresis after 1 day in the ENACT-HF trial [3]



The effect of the protocol was also seen in both natriuresis and diuresis on day 2. They were significantly higher in the group following the diuretic protocol (P<0.001 for both comparisons). No differences were seen in weight loss and congestion score after 2 days but, according to Dr Dauw, weight loss is possibly less reliable in a pragmatic design. “We had a high congestion score already at the beginning of the trial, it might therefore take more time for these patients to see a difference.” Patients following the standardised protocol had a 1-day shorter duration of hospitalisation. There were no differences in the safety endpoints between the standard-of-care and the diuretic protocol.

1. Mullens W, et al. Eur J Heart Fail 2019;21:137–55.
2. Metra M, et al. Eur J Heart Fail. 2023;Apr 26. Doi:10.1002/ejhf.2874.
3. Dauw J. Efficacy of a standardised diuretic protocol in acute heart failure. Session Late breaking clinical trials: acute heart failure and patients monitoring, Heart Failure 2023, 20–23 May, Prague, Czechia.

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Posted on 8 August 202327 March 2024