Implications for using SGLT2 inhibitors as treatment for patients with heart failure and reduced ejection fraction, regardless of whether they have diabetes based on DAPA-HF, a practice-changing study.
Darren K. McGuire, MD, MHSc: In the wake of the Type 2 diabetes trials proving the benefits of SGLT2 inhibitors, both on atherosclerotic cardiovascular disease outcomes and heart failure outcomes, the field raced to get into a broader space testing these drugs in heart failure. The DAPA-HF trial was the first that had been presented. There’s a similar trial ongoing with empagliflozin. These trials have enrolled patients with reduced-ejection fraction heart failure, independent of their diabetes status. In a great stroke of luck in DAPA-HF, it was roughly a fifty-fifty split. About half the patients had diabetes, and about half the patients did not have diabetes.
Everyone entering the trial had reduced-ejection fraction heart failure, and they were randomized, on top of outstanding evidence-based heart failure therapies, to receive dapagliflozin versus placebo. It was a remarkable superiority benefit both overall for cardiovascular death and hospitalization for heart failure, and for acute presentation with heart failure complications, which was the primary outcome. There was no difference whether the patients had or did not have diabetes.
This is a landmark, revolutionary trial in the heart failure spaces, specifically in heart failure with reduced ejection fraction. This now adds to the level 1A–indicated therapies like ACE inhibitors, ARBs, beta-blockers, and mineralocorticoid antagonists. We now have a brand-new class with robust evidence suggesting incremental benefit added to the best-available therapy up to that time. This is a landmark, practice-changing study, and my colleagues are already embracing this and using SGLT2 inhibitors routinely.
I am going to be thrilled if we get a second trial confirming that this is a class effect. Right now, all we know is that dapagliflozin has this benefit. I look very keenly to the results from the EMPA Acute Heart Failure trial with reduced-ejection fraction to confirm that this may be a class effect and that the use of all these agents may benefit such patients.