James Januzzi, MD: Prescribing After PROVE-HF Findings

How does the broadened sacubitril/valsartan assessment influence the treating confidence of a clinician?

Findings from the PROVE-HF trial, presented at the Heart Failure Society of American (HFSA) 2019 Scientific Sessions in Philadelphia, PA, showed sacubitril/valsartan (Entestro) benefitted patients with reduced ejection fraction heart failure (HFrEF) regardless of dosing titration over 1 year.

After discussing the overall findings and their implication for potential patients, investigator James Januzzi, MD, professor of medicine at Harvard Medical School, and of the Cardiology Division at Massachusetts General Hospital, talked to MD Magazine® about how PROVE-HF influences prescribing confidence for sacubitril/valsartan—and what more subgroup analyses are planned.

MD Mag: How do the PROVE-HF trial results influence the mindset of a prescribing physician?

Januzzi: Clinicians need to have confidence about the therapies they give to their patients. This is a relatively newer drug—although it's been out for a few years now. It does come with a price tag, which sometimes people are uncomfortable with. So, knowing just exactly what you're going to get for your patients I think is really important.

For clinicians, my message would be that this study mimics what we would see in real life. These are patients eligible for sacubitril/valsartan therapy, based on the approved indications for the drug. Initiated and titrated to the best dose that we could get. So unlike in PARADIGM—where patients were titrated all the way up to the top dose or they were removed from the trial—in PROVE-HF, we actually kept people who should not get to the top dose.

So for clinicians who try to titrate but can't get up to the maximal dose of sacubitril/valsartan, it's reassuring to know that these patients will still profit from being put on.

There are other important messages. The drug was well-tolerated, there was a minimal amount of side effects, no more than we would have expected based on prior experience. There was a little more dizziness, but really no major adverse events from the drug itself.

Very well tolerated, in particular, by a population of patients that has not been well studied in prior trials of sacubitril/valsartan, specifically blacks, where there was a prescribed risk for angioedema. Related to the drug, we saw only 1 case of angioedema out of over 220 patients of color in the study.

So the bottom line is that the trial really provides useful information to reassure our clinicians that this drug exerts a rather profound reverse cardiac remodellng effect—more so than any other drug that we have studied, together with obvious safety.

So really, in the end, it really provides a lot of reassurance.

MD Mag: What are the plans for follow-up assessment?

Januzzi: Further studies are definitely planned. We have now a team at the Mass General Heart Center—together with the other members of the steering committee of the trial, we designed PROVE-HF to examine numerous sub-studies after the completion of the main trial.

We have a very robust prior repository from which we'll be looking at the effects of sacubitril/valsartan on a wide range of biomarkers, to help us better understand mechanism of action and mechanism of benefit, and quality of life measures to see how the drug affected symptoms and quality of life across the whole year of management.

And other very important sub-studies, including subgroup analyses and important patients such as the older patients, women, people of color, and other important groups.