Initiating/Switching Therapy for Heart Failure

Transcript: Javed Butler, MD, MPH, MBA: May I ask you a quick question? In PARADIGM-HF, unlike PARADIGM and PIONEER-HF, there was a sizeable proportion of patients who were not on an ACE [angiotensin-converting enzyme] inhibitor with sort of known heart failure, although it wasn’t as big of a trial as PARADIGM-HF. But are you comfortable starting people with new-onset heart failure with valsartan/sacubitril, or would you always start with the ACE inhibitor first and then switch?

Scott David Solomon, MD: As you know, the PARADIGM-HF trial took patients already on ACE inhibitors and ARBs and then switched them over, even though, interestingly, the majority of those patients—about 60%—were not on optimal doses of ACE inhibitors or ARBs [angiotensin receptor blockers]. That trial didn’t really test that. But the PIONEER-HF trial did enroll some patients who were never on ACE inhibitors or ARBs previously. They did this safely. They did this even in the setting of relatively acutely decompensated heart failure.

I think that because valsartan is a component of sacubitril/valsartan, you are essentially giving an ARB when you give sacubitril/valsartan. It makes no sense to me, personally, to delay the initiation of a drug that we think is beneficial. We saw a very rapid improvement in outcomes in the PARADIGM-HF trial and PIONEER-HF trial with sacubitril/valsartan. Within a month, we saw separation of curves in PARADIGM-HF. So I don’t think it makes a whole lot of sense to spend a few months up-titrating an ARB and then switching a patient over. In the patient who has not been on an ACE inhibitor or ARB, you do want to start with a low dose. You can use the 50-milligram dose as a starting dose if you wish in those patients and then up-titrate if they tolerate it.

Javed Butler, MD, MPH, MBA: Thank you.

Deepak L. Bhatt, MD, MPH: Great. That’s really useful, practical advice. This is a very underused medication, and part of that is just unfamiliarity or how to start it and whom to start it in. So that’s really very practical and useful.

Transcript Edited for Clarity