Current guidelines recommend a standardized diuretic protocol for diuretic use that has not been evaluated prospectively. To test whether a standardized diuretic protocol is superior to standard of care, Dr. Jeroen Dauw performed the prospective, multicenter, open-label, nonrandomized, pragmatic ENACT-HF trial. The study included 29 centers in 18 countries worldwide. In each center, standard of care was compared with a standardized diuretic protocol in two sequential phases of recruitment: standard of care was used in phase 1, and the standardized protocol was followed in phase 2.

All 401 study participants had been admitted with acute heart failure (HF) and had at least one 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 hospitalization.

Following the standardized 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). A predefined subgroup analysis revealed that patients had a benefit independent of age, sex, kidney function, and left ventricular ejection fraction. “Those with a lower glomerular filtration rate had even a higher benefit,” Dr. Dauw said.

The superiority 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 difference was seen in weight loss and congestion score after 2 days, but weight loss may be 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,” Dr. Dauw said. Patients following the protocol had a 1-day shorter duration of hospitalization. There was no difference in the safety endpoints between standard of care and the diuretic protocol.

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