Added Ertugliflozin Heart Failure Data Show It’s Best in HFrEF

Additional data from the VERTIS CV trial for ertugliflozin (Steglatro, Merck/Pfizer) presented Monday during the European Society of Cardiology (ESC) 2020 Congress added to the evidence that the sodium glucose cotransporter 2 (SGLT2) class, first developed for type 2 diabetes (T2D), is effective in heart failure.

And, unlike the first cardiovascular outcomes trials that revealed how SGLT2 inhibitors could reduce hospitalization for heart failure, this latest round of data drilled down on specifics: it’s not enough to say a drug works in heart failure; clinicians want to know what type of heart failure patients benefit.

While the data from VERTIS CV presented in June during the American Diabetes Association Scientific Sessions found that ertugliflozin did not match its competitors in overall cardiovascular outcomes, heart failure was a bright spot. In those results, patients with T2D and atherosclerotic cardiovascular disease (ASCVD) saw their risk of heart failure hospitalization reduced by 30%.

In VERTIS CV, 24% of the patients had heart failure, a share that the investigators reported is consistent with the percentage of heart failure patients in the T2D population.

Data from the prespecified secondary analysis presented at ESC showed the following:

• Ertugliflozin reduced the risk of first and future heart failure by 30%.
• The drug was shown to reduce the risk of hospitalization for heart failure in patients whether or not they had a prior history of heart failure, a key finding since diabetes increases the risk of heart failure.

The importance of specifying ejection fraction

Results showed that ertugliflozin appeared to be more effective in patients whose ejection fraction was ≤45%, compared with those whose ejection fraction was >45% or unknown. Thus, it would appear the drug was more effective in patients with heart failure with reduced ejection fraction (HFrEF), as opposed to those with heart failure with preserved ejection fraction (HFpEF).

Two other SGLT2 inhibitors, empagliflozin and dapagliflozin, have already shown their efficacy in HFrEF whether or not patients have diabetes. Trials that are studying the drugs in HFpEF await results.

There are no therapies approved in HFpEF, although FDA is evaluating a drug from a different class, sacubitril/valsartan, which combines a neprilysin inhibitor and an angiotensin receptor blocker. That drug, already approved in HFrEF, just missed its primary end point in the PARAGON-HF trial for HFpEF but showed effectiveness for women and for patients with ejection fraction up to 57%.