Use of SGLT-2 Inhibitors in Heart Failure

EP: 1.Challenges in Heart Failure Management

EP: 2.Prevalence and Risk Factors of Heart Failure

EP: 3.Quadruple Therapy for Patients With Heart Failure

Now Viewing

EP: 4.Use of SGLT-2 Inhibitors in Heart Failure

EP: 5.Personalizing Quadruple Therapy in Heart Failure

EP: 6.Unmet Needs in the Management of Heart Failure

EP: 7.Clinical Trials of Sacubitril/Valsartan in Heart Failure

EP: 8.The Future of Heart Failure Therapy

Anuradha Lala-Trindade, MD: SGLT2 [sodium-glucose cotransporter-2] inhibitors are not the new kid on the block anymore, but it has been an exceedingly exciting time in heart failure by virtue of this class of drugs. There are a number of trials that have shown us the efficacy of these drugs in the treatment of heart failure across the spectrum of ejection fraction and across different settings of heart failure. So, acute heart failure as well as chronic heart failure. One of these trials was the DAPA-HF study, which studied dapagliflozin vs placebo in over 4700 adults with heart failure with reduced ejection fraction without diabetes. Dapagliflozin improved the primary endpoint of a combination of cardiovascular death or worsening heart failure.

This was followed by EMPEROR-Reduced, looking at dapagliflozin vs placebo in over 3700 patients, so 1000 patients less, with heart failure and reduced ejection fraction, again, without diabetes. It had the same clinical endpoint, a combination of cardiovascular death or heart failure hospitalizations. There was a similar relative reduction in this endpoint by virtue of empagliflozin, again suggesting a class effect. That's really along the lines of the reduced ejection fraction spectrum.

Then we move over to SCORED. This is building up the platform for sotagliflozin, which was recently FDA-approved. Sotagliflozin vs placebo. SCORED was a very large study, over 10,000 individuals. These are individuals with type 2 diabetes and chronic kidney disease, so a slightly different population to keep in mind. The composite endpoint consisted of cardiovascular death, heart failure hospitalizations, as well as urgent heart failure visits. Again, a similar 25% relative reduction in that composite endpoint with sotagliflozin vs placebo.

Then, we move on to SOLOIST-WHF. SOLOIST-WHF was sotagliflozin vs placebo, in about 1200 patients. And remember this spanned the COVID-19 pandemic as well. These patients all, again, had diabetes and worsening heart failure recently. So a recent heart failure hospitalization. In fact, over 40% were actually in-patient at the time of enrollment. Again, the composite endpoint was cardiovascular death, heart failure hospitalizations, heart failure urgent visits, and this showed a profound reduction of 33%, in this composite endpoint. So, we've moved from dapagliflozin and empagliflozin in the chronic heart failure with reduced ejection fraction setting. Then you've got [a trial] looking at sotagliflozin, which is a combined SGLT1 and 2 inhibitor, primarily in a diabetic population, either with CKD [chronic kidney disease] or worsening heart failure.

Then we move into the preserved ejection fraction sphere. So, we have EMPEROR-Preserved, with empagliflozin vs placebo and a little under 6000 patients with chronic heart failure with preserved ejection fraction. It had the same endpoint cardiovascular death and heart failure hospitalizations. There was a reduction of over 20% in that endpoint. And the DELIVER trial, which was dapagliflozin vs placebo. Over 6000 patients with chronic heart failure and preserved ejection fraction. It had the same endpoint, and a similar reduction in that primary endpoint.

So, across the spectrum, whether you look at dapagliflozin, empagliflozin, or the SGLT1 and 2 inhibitor, sotagliflozin, you're seeing similar reduction in the composite cardiovascular death and heart failure hospitalizations across the spectrum of ejection fraction. What I didn't speak about was the EMPULSE trial in the acute heart failure setting. That was assessed slightly differently, looking at a win ratio. Again, showing efficacy of starting SGLT2 inhibitors in the hospital to prevent outcomes with very quick time to efficacy. And so, I think that the effects of these drugs are appreciated very early on in their administration.

Transcript edited for clarity