麻豆传媒

NATIONAL HARBOR, Md. -- In acute heart failure (AHF), salt supplementation during aggressive diuretic therapy didn't appear to mitigate neurohormonal activation in a randomized placebo-controlled trial -- but it didn't hurt outcomes either, challenging the usual low-sodium paradigm in heart failure.

At one center, hospitalized patients with AHF taking sodium chloride pills three times daily during IV diuresis had no different changes in creatinine and weight at 96 hours compared with peers randomized to placebo pills instead. Both groups lost weight and experienced a small increase in creatinine, according to Robert Montgomery, MD, of Case Western Reserve University and University Hospitals Cleveland Medical Center.

Oral sodium chloride was associated with no change in other secondary outcomes except for a smaller decrease in serum sodium and a smaller increase in blood urea nitrogen over hospitalization, Montgomery reported in presenting the OSPREY-AHF trial results at the Heart Failure Society of America (HFSA) annual meeting.

"While underpowered, the absence of demonstrable harm to sodium chloride during IV diuretic therapy suggests that larger clinical trials are possible, and necessary," Montgomery said. "Not all the teaching about sodium is thrown out the window."

Montgomery reasoned that while low sodium can aid decongestion in theory, it can also be associated with decreased nutritional quality and caloric intake and increased neurohormonal activation, leading to more RAAS activation and renal sodium avidity and a lower diuretic response.

Thus, some had suggested supplementing salt in the form of hypertonic saline to mitigate this neurohormonal activation. Previous reports supported infusing salt to facilitate more urination with high-dose diuretic drugs in patients with congestive heart failure.

Montgomery compared the 6 g/day sodium chloride intervention with the 4.5 g of sodium chloride in a typical 3% NaCl hypertonic saline solution and the 5.25 g in six large French fries.

"Since the 1940s we've been taught that salt is the main reason why people become congested with fluid, which led to the idea that we need to keep people low on salt while in the hospital with fluid overload," said co-author Wilson Tang, MD, of Cleveland Clinic, where the trial was conducted.

"Our findings do not mean that patients with heart failure should start eating more salt, as we only studied the role of oral salt supplementation in those receiving high-dose diuretic drugs during their hospitalizations," Tang cautioned in a . "Patients with heart failure still need to be mindful that excessive salt intake may cause fluid congestion."

Montgomery reminded the HFSA audience that the current guidelines give no strong recommendations on dietary sodium restriction in AHF, citing an evidence gap.

OSPREY-AHF was conducted from June 2020 to July 2022. Exclusion criteria included hypernatremia or severe hyponatremia, concurrent acute coronary syndrome, kidney failure, people already using sodium chloride tablets, and those not able to swallow or absorb the pills.

The double-blind trial had started with 183 individuals screened for enrollment, of whom 70 consented. Participants were randomized to pills containing 2 g NaCl (n=34) or placebo (n=31) in addition to the hospital-provided 2 g sodium-restricted diet. A few individuals had withdrawn after seeing the "ginormous" pills they would have to swallow for the study, Montgomery reported.

Mean age was 70 years, with women accounting for 37% of participants. Most people had hypertension and atrial fibrillation, and ejection fraction was mildly reduced on average. People largely had two prior hospitalizations in the past year and were on furosemide infusions at approximately 15 mg/hour.

Chronic kidney disease was at stage IIIb overall at baseline, as the average eGFR was 39 mL/min/1.73 m². Most people were on beta-blockers, mineralocorticoid receptor antagonists, and hydralazine-isosorbide dinitrate therapy. In contrast, there was limited use of RAAS inhibitors and SGLT2 inhibitors.

Vital signs showed normal heart rate and blood pressure at enrollment. Patients reported moderate thirst on a survey.

The trialists did not find significant differences between the sodium chloride and placebo groups in terms of serious adverse events like 30-day readmissions or death at 90 days. There was no change in blood pressure at the end of the study.

However, OSPREY-AHF was not powered for a safety analysis, Montgomery acknowledged.

He added that in testing the neurohormonal hypothesis, the oral sodium chloride approach in OSPREY-AHF does not fully replicate hypertonic saline.

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