Dapagliflozin (Farxiga) seems to be no simpler than the “thiazide-like” diuretic metolazone at enhancing pulmonary congestion and fluid standing in sufferers with acute coronary heart failure (AHF), suggests a brand new randomized trial. The medicine got to the research’s loop-diuretic–resistant sufferers on prime of furosemide.
Modifications in quantity standing and measures of pulmonary congestion and danger for severe adversarial occasions had been comparable for these assigned to take dapagliflozin, an SGLT2 inhibitor, or metolazone, a quinazoline diuretic. These on dapagliflozin zone finally acquired a bigger cumulative furosemide dose within the 61-patient trial, known as DAPA-RESIST.
“The subsequent steps are to evaluate whether or not a technique of utilizing SGLT2 inhibitors up entrance in sufferers with HF reduces the incidence of diuretic resistance, and to check additional combos of diuretics resembling thiazide or thiazide-like diuretics, in comparison with acetazolamide, when used along with an IV loop diuretic and SGLT2 inhibitors collectively,” Ross T. Campbell, MBChB, PhD, College of Glasgow and Queen Elizabeth College Hospital, United Kingdom, instructed theheart.org / Medscape Cardiology.
Campbell introduced the findings Might 21 on the Coronary heart Failure Affiliation of the European Society of Cardiology (HFA-ESC) 2023 and is senior creator on its simultaneous publication within the European Coronary heart Journal.
The multicenter trial randomly assigned 61 sufferers with AHF to obtain dapagliflozin at a set dose of 10 mg as soon as each day or metolazone 5 mg or 10 mg (beginning dosage at doctor discretion) as soon as each day for 3 days of remedy on an open-label foundation.
Sufferers had entered the trial on furosemide at a imply each day dosage of 260 mg within the dapagliflozin group and 229 mg for these assigned metolazone; dosages for the loop diuretic within the trial weren’t prespecified.
Their median age was 79 and 54% had been ladies; 44% had HF with decreased ejection fraction. Their imply glomerular filtration price was under 30 mL/min/1.73 m2 in 26%, 90% had power kidney illness, 98% had peripheral edema, and 46% had diabetes.
The imply cumulative furosemide dose was considerably greater among the many dapagliflozin group’s 31 sufferers, 976 mg vs 704 mg for the 30 on acetazolamide (P < .05), 96 hours after the beginning of randomized remedy. Nevertheless, sufferers on dapagliflozin skilled a lesser enhance in creatinine (P < .05) and in blood urea (P < .01), a higher change in serum sodium (P<.05), and a smaller discount in serum potassium (P < .01).
Though the trial wasn’t powered for these outcomes, Campbell stated, “Much less biochemical upset might be related to higher outcomes by way of much less medium- to long-term renal impairment, and within the short-term size of keep.”
The imply lower in weight at 96 hours, the first endpoint, reached 3 kg on dapagliflozin in comparison with 3.6 kg with metolazone (P = .082), a distinction that fell in need of significance.
Loop diuretic effectivity, that’s weight change in kg per 40 mg furosemide, “was smaller with dapagliflozin than with metolazone at every time level after randomization, though the distinction was solely important at 24 hours,” the revealed report states.
Modifications in pulmonary congestion (by lung ultrasound) and fluid quantity had been comparable between the teams.
“This trial additional provides to the proof base and security profile for utilizing SGLT2 inhibitors in sufferers with acute coronary heart failure,” and “provides additional confidence to clinicians that this class might be began in ‘sicker’ sufferers with HF who even have diuretic resistance,” Campbell stated.
Requested throughout his presentation’s query and reply whether or not dapagliflozin might need proven a higher impact had the dosage been greater, Campbell defined that the drug was investigational when the trial began. Including a higher-dose dapagliflozin arm, he stated, would have made for an excessively complicated research. However, “that’s an ideal analysis query for one more trial,” he stated.
DAPA-RESIST was funded by AstraZeneca. Campbell disclosed receiving honoraria from AstraZeneca for talking and from Bayer for serving on an advisory board.
Coronary heart Failure Affiliation of the European Society of Cardiology 2023. Late-Breaking Science. DAPA-RESIST scientific trial – Dapagliflozin versus metolazone in coronary heart failure with diuretic resistance. Introduced Might 21, 2023.
Eur Coronary heart J 2023. Revealed on-line Might 21, 2023. Abstract
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