Diuretics for Ambulatory HF Patients With Volume Overload: Winners & Losers

Diuretics for Ambulatory HF Patients With Volume Overload: Winners & Losers


Three regimens in comparison head-to-head amongst great choices

by
Nicole Lou,

Senior Workers Creator, MedPage Instantly

July 10, 2024

For patients with power heart failure (HF) who possess power congestion despite excessive doses of oral loop diuretics, the very most practical choice to intensify diuretics within the outpatient environment will be narrowed, per a microscopic randomized crossover detect.

Comparing the potency of three diuretic regimens in ambulatory congestion-refractory patients, investigators within the DEA-HF trial reported vastly extra total sodium excretion at 6 hours with excessive-dose IV furosemide plus oral metolazone (4,691 mg), which beat furosemide alone (3,835 mg, P=0.015) and furosemide plus acetazolamide (3,584 mg, P=0.001).

As for total urinary quantity excreted, the very most practical outcomes had been seen with furosemide plus metolazone (1.84 L) and furosemide alone (1.71 L), in comparison with furosemide plus acetazolamide (1.58 L, P=0.039), reported Oren Caspi, MD, PhD, of Rambam Health Care Campus in Haifa, Israel, and colleagues in JACC: Coronary heart Failure.

The investigators acknowledged their total outcomes make stronger the older CLOROTIC and 3T trials.

Nonetheless, the modest difference in urine volumes with and with out metolazone led Paula Rambarat, MD, and G. Michael Felker, MD, MHS, both of Duke University School of Medications in Durham, North Carolina, to avoid wasting a question to of the scientific significance of the sodium excretion knowledge.

“Demonstrating a major expand in natriuresis between two treatment arms is per chance purely tutorial if a subsequent boost in significant scientific endpoints equivalent to markers of congestion or rates of hospitalizations can no longer be accomplished,” they wrote in an accompanying editorial comment.

Moreover, there used to be a downside to furosemide plus metolazone: a vastly increased fee of worsening renal characteristic (39%) versus furosemide alone (16%) and furosemide plus acetazolamide (2.6%). However, this didn’t translate into extra hospital admissions attributable to acute kidney injury as the predominant motive, detect authors mighty.

Finally, acetazolamide didn’t lead to higher natriuresis, urine quantity, or weight gash worth as an add-on to excessive-dose IV furosemide, in accordance with Caspi’s team — unlike the ADVOR trial, which learned that lower-dose furosemide plus acetazolamide did certainly present a profit.

The diminishing returns of this combination within the fresh trial will be connected to furosemide having been tested at a increased dose in DEA-HF, they theorized, or the greater preponderance of background SGLT2 inhibitor (SGLT2i) exhaust precluding the ability of acetazolamide to expose a profit.

“From a physiological standpoint, SGLT2is and acetazolamide both block sodium reabsorption within the proximal tubule of the nephron … On a background of excessive SGLT2i exhaust, the addition of intravenous acetazolamide to a loop diuretic might per chance per chance no longer be as effective at augmenting diuresis,” wrote Rambarat and Felker.

Moreover complicating the selection of diuretics is the provision of a comparatively fresh subcutaneous formulation of furosemide that might per chance even be self-administered by patients at house.

“Future reviews are wished to match outcomes with subcutaneous furosemide vs combination therapy with intravenous furosemide within the ambulatory, congestion-refractory HF population. As well, whether or no longer combination therapy with metolazone as well as to subcutaneous furosemide improves outcomes is unknown,” Rambarat and Felker entreated.

“Importantly, although the proof of diuretic set is within the urine, these future doable reviews might per chance per chance well also peaceable ideally be adequately powered to assess symptom burden and HF hospitalizations as significant scientific endpoints. It is handiest through such significant work that the characteristic of outpatient parenteral diuretic therapy within the administration of the congestion-refractory HF patient will even be established,” the editorialists concluded.

DEA-HF used to be a doable detect conducted in 2023 in a single day-care heart failure unit located in-hospital.

Eligible patients had been power HF patients with New York Coronary heart Association class II to IV indicators and no longer no longer up to one signal of congestion while taking no longer no longer up to two HF tablets. Moreover, they needed to expose estimated glomerular filtration rates greater than 20 mL/ min/1.73 m2 and have not any history of renal replace therapy or ultrafiltration 30 days before randomization.

In their crossover detect, investigators had 42 of us subjected to a random sequence of weekly treatment with IV furosemide 250 mg, IV furosemide 250 mg plus oral metolazone 5 mg, or IV furosemide 250 mg plus IV acetazolamide 500 mg. Treatments had been administered as soon as per week for total detect participation lasting 3 consecutive weeks in total.

The proportion of of us finishing your total sequence of therapies and note-up reached 88%.

Amongst all enrolled patients, mean age used to be 72 years, and 40% had been females. Half had left ventricular ejection fraction 50% or increased. Three-quarters had been in New York Coronary heart Association class III. All had been on excessive-dose oral loop diuretic agents at baseline and most patients had been on tenet-directed scientific therapy along side SGLT2 inhibitors.

The incidence of electrolyte abnormalities and symptomatic hypotension used to be the same between teams.

Caspi and colleagues acknowledged the doable of carryover outcomes between therapies despite discovering no statistical proof of this. With DEA-HF as a single-heart detect, additionally it is shrimp in its generalizability to other settings, and attempts to conduct it as a multicenter trial would be impractical, the authors cautioned.

  • author['full_name']

    Nicole Lou is a reporter for MedPage Instantly, where she covers cardiology news and other traits in treatment. Apply

Disclosures

No funding sources for the trial had been reported.

Caspi had no disclosures. Eye co-authors reported diversified ties to business, along side Edwards Lifesciences, Boehringer Ingelheim, Bayer, AstraZeneca, Novo Nordisk, Pfizer, and Vectorious Clinical Applied sciences.

Felker reported broad relationships with business; Rambarat declared no connected monetary interests.

Main Supply

JACC: Coronary heart Failure

Supply Reference: Abbo A, et al “Diuresis efficacy in ambulatory congested heart failure patients: intrapatient comparison of three diuretic regimens (DEA-HF)” JACC Coronary heart Fail 2024; DOI: 10.1016/j.jchf.2024.04.014.

Secondary Supply

JACC: Coronary heart Failure

Supply Reference: Rambarat P, Felker GM “Decongestion programs for ambulatory outpatients: the proof is within the urine” JACC Coronary heart Fail 2024; DOI: 10.1016/j.jchf.2024.05.010.

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