Dr Zachary Cox: Early Dapagliflozin Modestly Improves Diuresis, Decongestion for Patients With ADHF

Zachary Cox, PharmD, professor at Lipscomb University College of Pharmacy, explains the main findings of DICTATE-AHF, which assessed how early initiation of sodium glucose co-transporter 2 (SGLT2) inhibitor dapagliflozin affects diuretic efficiency compared with standard of care in patients hospitalized with acute decompensated heart failure. While the primary endpoints did not reach statistical significance, Cox highlights the value of the positive safety and efficacy findings.

Transcript

What were the main findings of DICTATE-AHF?

We know a lot about SGLT2 inhibitors when they're started at the end of a hospital stay or in clinic and look at their intermediate to long-term benefits—we know these drugs are very beneficial for patients with heart failure. But there's a knowledge gap for in the hospital regarding the safety and efficacy of these, and that's what DICTATE-AHF was designed to look at, the safety and efficacy of starting dapagliflozin within 24 hours of hospitalization, and looking at its effects over the 5 days of heart failure hospitalization or until discharge.

We randomized 240 patients within 24 hours of heart failure hospitalization presentation to either dapagliflozin 10 milligrams daily or placebo and followed them until discharge or day 5, whichever occurred first, and then we followed them for safety up to 30 days after hospitalization. I think it makes sense to discuss the findings in terms of the 2 goals of the acute heart failure hospitalization. The 2 goals are decongestion—safely getting fluid off of patients—and then safely optimizing guideline-directed medical therapy, and that's where the efficacy and safety of DICTATE came in.

First, safety. We looked at prespecified safety outcomes across diabetes, cardiovascular, and kidney outcomes, and these were adjudicated by a blinded committee. What we looked at and found was that dapagliflozin started on the first day of heart failure hospitalization was safe across diabetes-related outcomes. It did not lower blood sugar more often than usual care [and] it didn't result in any episodes of diabetic ketoacidosis.

We looked across cardiovascular safety events and found that dapagliflozin did not increase the risk of worsening heart failure or of hypotension events. And then we looked across kidney outcomes and found that dapagliflozin did not increase the risk of lowering median eGFR [estimated glomerular filtration rate] relative to usual care, or of increasing the risk of genital urinary tract infections.

Then, when we looked at [efficacy], our primary efficacy outcome was diuretic efficiency. This looked at, over the 5-day study period, the cumulative weight loss divided by the cumulative dose of IV [intravenous] loop diuretics required to achieve that weight loss, and compared that with usual care with adding dapagliflozin, [and asked,] "Did dapagliflozin reduce this?" We put this into an odds model that was adjusted for baseline weight. What we found is that the odds ratio favored dapagliflozin with a 0.65, but this just narrowly missed statistical significance with the upper limit of the 95% confidence interval being 1.01 and the P value being .06.

The totality of the evidence, though, really suggested dapagliflozin does help with some modest diuretic end points. We found that it increased 24-hour urinary sodium excretion relative to usual care, increased 24-hour measured urine output compared to usual care, decreased the time to completing IV diuresis, and decreasing the time to hospital discharge. So the totality of the evidence suggests that there's a modest diuretic benefit of adding dapagliflozin early in the hospital stay.

For context, what is the current standard of care?

The standard of care in this trial was not starting dapagliflozin for the first 5 days of the hospital stay. After the study, patients could start at open label either at discharge or in the clinic setting, which would be the usual standard of care. This was structured standard of care, so we standardized the IV loop diuretic regimen that patients received so both treatment arms were titrated to a goal urine output of 3 to 5 liters per day—so a very aggressive urine output goal—and then we standardized the background insulin therapies that were adjusted by endocrinologists via protocol.