Clinical Trials of Sacubitril/Valsartan in Heart Failure

Anuradha Lala-Trindade, MD: Recently we’ve gained information as to the effects of sacubitril/valsartan on NT-proBNP [N-terminal prohormone of brain natriuretic peptide] amongst patients with acute heart failure. So, these were not patients who were included in the PARAGON-HF study who had chronic heart failure with preserved ejection fraction [HFpEF], nor quite frankly, was there an adequate representation of individuals of Black race in PARAGON-HF, as well. PARAGLIDE-HF really served to fill these gaps in that it looked at an acute heart failure population. It really sought to have diverse enrollment, which was really important.

What we saw from that study really extended what we learned from PARAGON-HF as well across a different setting, which is that ARNis [angiotensin receptor/neprilysin inhibitors] do reduce NT-proBNP, which we know is a very powerful surrogate for clinical outcomes. Of course, this trial wasn’t adequately powered for clinical outcomes. However, we see suggestions that there was an improvement in clinical outcomes, particularly in the renal outcomes in this population.

I would say for me, personally, my practice remains the same. I’m still reaching for an ARNi in those patients with an adequate blood pressure because we have to remember from PARAGLIDE-HF that we did see a higher incidence of symptomatic hypotension. So, in those patients with an adequate blood pressure, I’m still reaching for ARNi across the spectrum of ejection fraction and across different settings, where appropriate.

I think what was really nice about PARAGLIDE-HF was that it sought to fill gaps in knowledge and in evidence, and I really appreciate the way the trial was conducted. It sought to include diverse populations; 50% women, and high prevalence of Black patients, as we already mentioned. Patients included a high BMI, which were not previously included in PARAGON-HF. And also de novo heart failure with preserved ejection fraction or mildly reduced ejection fraction. And so it expands our knowledge and our evidence base for use of this particular agent across more generalizable populations.

I think it’s important to keep in mind blood pressure. I think it’s important to keep in mind that only 12% of patients in that study were on SGLT2 [sodium-glucose cotransporter-2] inhibitors, so I still think that there’s a greater body of evidence to support the use of SGLT2 inhibitors in HFpEF or across the ejection fraction spectrum. But certainly, ARNi should be considered in those patients with blood pressure room and who met the criteria of the trial, which was really a broad population. So, I think it just offers us additional evidence.

Transcript edited for clarity