Advancing Decongestive Strategies in Acute Heart Failure

Despite advancements in medical and device therapies for heart failure (HF), a significant number of patients are admitted and readmitted to the hospital for acute decompensation. The management of these patients has changed little in the last 30 years, with loop diuretics still the cornerstone of decongestive therapy.

Recent literature also highlighted the need to pair guideline-directed medical therapy (GDMT) optimization as an important second priority in addition to decongestion for patients admitted for ADHF. Sodium-glucose linked transport protein 2 (SGLT-2) inhibitors can accomplish both of these goals, as they are one of the pillars of GDMT, and they have been shown in preliminary studies to assist with decongestion in patients with acute decompensated HF (ADHF). In this installment of Talking Therapeutics, we explore a new randomized trial evaluating the safety and efficacy of early dapagliflozin initiation in patients with ADHF.

Talking Point: Clear Signals for Safety and Efficacy

In a new study, 240 patients were randomized within 24 hours of hospital presentation for ADHF and were administered dapagliflozin 10 mg once daily or received traditional care with protocolized diuretic titration. The primary outcome was diuretic efficiency expressed as cumulative weight change per cumulative loop diuretic dose.

For diuretic efficiency, there was no difference between dapagliflozin and usual care (OR: 0.65; 95% CI: 0.41-1.02; P=0.06). However, dapagliflozin was associated with reduced loop diuretic doses (560 mg versus 800 mg, P=0.006) and fewer intravenous diuretic up-titrations (P≤0.05) to achieve equivalent weight loss as usual care. Dapagliflozin was also associated with improved urine output, which expedited hospital discharge over the study period.

Importantly, early dapagliflozin initiation did not increase diabetic, renal, or cardiovascular safety events.

Talking Point: SGLT2s are Now the Standard of Care

I can see how one would look at this trial and say that it missed its primary endpoint, and is not confirmatory, but I strongly disagree. We already know that SGLT2 inhibitors reduce rates of cardiovascular mortality and HF hospitalizations, so they should be started in all hospitalized patients for these reasons alone. They also enhance diuretic efficacy and can speed up decongestion, which is just icing on the cake.

Other add-on therapies to loop diuretics—like thiazide diuretics and tolvaptan—do not convey any additional cardiovascular benefits like the SGLT2 inhibitors do. These agents can cause dangerous side effects like electrolyte disturbances. Combining all of these facts, and it’s a no-brainer that SGLT2 inhibitors should now be considered the preferred agents to add to loop diuretic therapy in patients with ADHF.