Starting dapagliflozin (Farxiga) early during acute heart failure hospitalization did not promote decongestion but appeared to save loop diuretic doses and increase diuresis compared with usual care. This was shown in the DICTATE-AHF study.

Diuretic efficiency (cumulative weight change per cumulative dose of loop diuretic) was not significantly better for SGLT2 inhibitors (SGLT2i) than standard diuretic titration (OR 0.65, 95% CI 0.41- 1.02, P=0.06), Zachary Cox, Ph.D., Lipscomb University School of Pharmacy, Nashville, Tennessee, and colleagues. Journal of the American College of Cardiology.

However, patients treated with dapagliflozin in open-label trials received lower loop diuretic doses (560 mg vs. 800 mg; P=0.006), less titration of IV diuretics (P≤0.05).

Furthermore, the researchers emphasized that the strategy of starting within 24 hours of admission appears to be safe with no excess diabetic, renal, or cardiovascular safety events. Despite neutral results for the primary endpoint, “safety findings should encourage early in-hospital use, which could lead to improved chronic SGLT2i prescribing, adherence, and long-term benefits.” There is a sex.”

Cox et al. write that only about 20% of eligible acute heart failure patients are started on SGLT2 inhibitors in the hospital, primarily due to safety concerns. In fact, “endocrinology guidelines and international diabetes experts recommend routine use of SGLT2i during hospitalization due to concerns about increased risk of urogenital infections, ketoacidosis, and acute kidney injury.” plug.”

Evidence from clinical trials is strong for use in chronic heart failure and in-hospital initiation of acute heart failure, said Maria Rosa Costanzo, MD, of the Midwest Heart and Vascular Institute in Naperville, Illinois, and James of Massachusetts General Hospital and Harvard University.・Gianuzzi, MD, said: The Boston thing is noted in an accompanying editorial.

Based on evidence from previous clinical trials, “the rationale for why SGLT2i should be initiated during hospitalization is that the treatment is safe and promotes adherence,” the researchers wrote. This study corroborates the results of a similar pilot study with a similar SGLT2 inhibitor, empagliflozin (Jardiance), and adds rationale for reducing doses of IV loop diuretics. Costanzo and Januzzi noted that this may reduce the contribution to the “vicious cycle of neurohormonal activation that accelerates the progression of cardiorenal failure.” ”

Additionally, “the effects of these drugs go far beyond enhancing decongestion, with SGLT2 having unique effects on cardiomyopathy and nephropathy progression” with proven long-term effects on outcomes. wrote the editorial board.

Nevertheless, they cautioned that the study had limitations that could not be overlooked. “Of the 3,672 patients screened for eligibility, only 7% were randomized. This raises questions about whether the enrolled subjects are representative of her AHF. I’ll let you do it.” [acute heart failure] It is based on populations seen in clinical practice and therefore the generalizability of the study results. ”

Researchers highlighted that screening procedures leading up to enrollment during the COVID-19 pandemic, and that before protocols were amended and approved, a third of screen failures They noted that 1 were patients without acute heart failure, and the remaining one-fifth were patients without type 2 diabetes.

The multicenter, open-label DICTATE-AHF study included 238 patients with acute heart failure who received dapagliflozin 10 mg daily within the first 24 hours of admission or per protocol until day 5 or discharge. The patients were randomly assigned to receive a dose adjustment of diuretics. The trial initially enrolled only adult patients with type 2 diabetes with an estimated glomerular filtration rate (eGFR) of at least 30 mL/min/1.73 m.² The protocol was modified to allow use in patients without type 2 diabetes and with eGFR as low as 25 mL/min/1.73 m, along with at least two objective measurements of hypervolemia.² After publication of safety data from the DAPA-HF study.

In fact, Cox et al. concluded that “Despite aggressive IV diuresis in DICTATE-AHF, dapagliflozin did not worsen eGFR or cause significant acute kidney injury events compared with usual care. Importantly, this was not the result of empirical IV loop diuretic dose reduction in DICTATE-AHF.” The acute and mild changes in eGFR caused by SGLT2i may be masked by the underlying fluctuations common to eGFR increases and decreases during decongestion in AHF. ”

Overall adverse event rates were similar between randomized groups. Dapagliflozin did not increase the risk of hypoglycemia (7 vs. 9 patients), and no ketoacidosis occurred in either treatment group.

Among the secondary endpoints, the researchers noted that “an additional 80 mg of IV furosemide was required in the usual care group to achieve 24-hour natriuresis comparable to that in the dapagliflozin treatment group.” Dapagliflozin also significantly increased 24-hour urine output (median 634 vs. 403 mL per 40 mg IV furosemide; P=0.005).

The researchers acknowledged that the limitations of the open-label design and modest sample size may have contributed to the lack of statistical significance for the moderate treatment effect in favor of dapagliflozin. Ta.

The editors also noted missing data on doses of relevant background therapy, lack of objective measurements of hypervolemia and decongestion as a condition for discharge, and a deplorable choice of primary endpoint. “Weight measurements have long been recognized to be unreliable” in heart failure patients both in hospitals and outpatient settings. ”

“At this stage, clinicians need to understand when to start proven treatments for AHF and which treatments, such as SGLT2is, can be started early,” Costanzo and Januzzi concluded. “Now we know why: SGLT2 improves decongestion and ensures good long-term use in outpatient settings.”