How Will DICTATE-AHF Findings Affect Clinical Practice? Dr Zachary Cox Explains

After detailing the findings of DICTATE-AHF—which demonstrated the benefits of sodium glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin for patients hospitalized with acute decompensated heart failure—Zachary Cox, PharmD, professor at Lipscomb University College of Pharmacy, explains why the study focused on patients with type 2 diabetes and the next steps for implementing these findings into clinical practice.

Transcript

What do the findings of DICTATE-AHF mean for cardiologists treating patients with type 2 diabetes?

These findings mean several things for cardiologists treating patients with type 2 diabetes. The first is that the benefits of this drug are equal whether patients did or did not have type 2 diabetes, we included both groups of patients. However, the safety concerns were that patients with type 2 diabetes may be at greater risk of having some of these adverse events. We found that this was not the case, and so it can give clinicians the confidence, even in patients with type 2 diabetes where they may be concerned of increasing low blood sugars or worsening other adverse events, that starting dapagliflozin on the first day does not increase these risks during the hospital setting or the immediate 30-day follow up period.

Aside from its general link with obesity, what made you specifically want to look at patients with type 2 diabetes in this trial?

We wanted to specifically include patients with type 2 diabetes in the study because patients with type 2 diabetes are at some of the greatest risks of cardiovascular disease. They're also at some of the greatest risk of the therapies that we use to lower those benefits. And we know that when patients with diabetes come into the hospital, they're at higher risk of hypoglycemia from the insulin therapies, they could be at greater risk of ketoacidosis from stopping them from eating for various procedures or low food intake during a time of critical illness. We specifically wanted to evaluate this and show that dapagliflozin was safe, even in these patients with these heightened risks, and these questions have been specifically raised by the International Society of Endocrinology as questions that deserve randomized clinical trial evidence.

Were there any patient behaviors during the trial that should be noted?

Some of the things that were really notable, particularly about the patient behavior throughout the trial, was that despite having standardized IV [intravenous] diuretics that were aggressively dosed—the median dose of IV furosemide per day in the usual care [was] almost 240 milligrams per day of IV furosemide, so these diuretics were aggressively titrated to urine output goal—dapagliflozin still provided diuretic benefit when we look at 24-hour urine sodium excretion and 24-hour urine output. Then we noted a dramatic difference or lowering of the loop diuretic doses that were needed very early on in the study in patients who were put on dapagliflozin, so they required less uptitration and a shorter duration of IV diuretic therapy. So, starting dapagliflozin on the first day, across multiple outcomes of its diuretic efficacy, showed that it reduced the need in the duration of IV loop diuretic therapy to achieve decongestion.

What are the next steps for implementing these findings into clinical practice?

The direct clinical applications right now are, [as] our first step, clinicians can be emboldened to safely start SGLT2 inhibitors early in the first day of an acute heart failure episode. We know that 80% of patients who are candidates for SGLT2 inhibitors are not started on these therapies prior to leaving the hospital.

One of the main concerns driving that is safety, and so we've answered that question. I think clinicians can start these drugs early, and that gives them time to adjust the other therapies even later in the hospital stay so that patients hopefully leave on even better optimal medical therapy.

In terms of efficacy, I think the findings here are that the standard of care should be to start an SGLT2 inhibitor along with IV loop diuretics on the first day of hospital stay and then add other diuretic therapies only in patients who are not meeting their decongestive goals.

When we extrapolate this out to other SGLT2 inhibitors, we can't say anything with certainty, but a lot of the other effects in heart failure across SGLT2 inhibitors seem to be fairly similar across this class. We would presume this to be a class effect, but would require further study to know that for sure.