Heart Failure Drug Management Tips and Tricks: The Foundational Four and Backup Plans

Ileana L. Piña, MD, MPH; Carolyn Lam, MBBS, PhD


September 29, 2021

This transcript has been edited for clarity.

Ileana L. Piña, MD, MPH: Hello. I'm Ileana Piña from Central Michigan University in Michigan, and an adjunct professor of epidemiology and biostatistics at Case Western Reserve University. This is my blog.

This is our third conversation this year at the European Society of Cardiology (ESC) Congress, which is being held in Amsterdam. This is a terrific meeting that many of us have attended in the past because we start to see the new stuff coming out. The late-breaking trials are always exciting, and they usually get published at the same time. This year, we have a richness of heart failure stuff. We're going to have to decide how we're going to apply all this to that patient who's sitting in front of us in clinic.

With me today is a very dear friend, Dr Carolyn Lam from Singapore. Carolyn is a professor at the Duke University Singapore and a consultant for the National Institutes of Health. She spent time in Framingham and has been a spokesperson for Framingham, and I've heard her deliver some beautiful lectures on things like pulmonary hypertension.

Carolyn Lam, MBBS, PhD: Ileana, you've forgotten my most important title. I'm the chairperson of the Ileana Piña fan club.

Piña: I did not pay you to say that, but thank you. You're also a wonderful mom of a beautiful baby.

Carolyn and I are going to have a chat. We have vericiguat, which is now approved in the United States, and omecamtiv mecarbil is in the works, I think, of being approved.

We are all in love with the sodium-glucose cotransporter 2 (SGLT2) inhibitors, regardless of which one, because they all have very similar findings, but we can't forget our good old renin-angiotensin-aldosterone system (RAAS) inhibition, our mineralocorticoid receptor antagonists (MRAs), and we certainly can't forget our beta-blockers. The beta-blockers do take uptitration time. The SGLT2 inhibitors don't need to be uptitrated, so that makes it a little bit easier. With vericiguat and sacubitril-valsartan, you start at a low dose and you move to a higher dose.

How are we going to do this, Carolyn? How are we going to put it all together, and what kind of conversations do we need to have with our patients? Where is precision medicine in all of this?

Lam: I would say the short answer is by simplifying and by keeping the aim very clear in our minds when we see a patient with heart failure with reduced ejection fraction (HFrEF).

First, let's talk about seeing a patient in an outpatient setting who's not acutely unstable, does not have cardiogenic shock, and is not congested. In that situation, it's really very clear for me. I know the foundational four: the angiotensin receptor-neprilysin inhibitor (ARNI), beta-blocker, MRA, and SGLT2 inhibitor. Honestly, just keep it simple and try to get the patient on all of these as quickly as possible.

I would suggest that you do not leave a gap in the mechanisms at the expense of uptitrating. That's my principle. You could run out of blood pressure space from trying to get the ARNI to the very highest doses really quickly and therefore can't even give a little bit of beta-blocker. I don't do that. I really think it's important that a patient has at least some beta-blockade if they're in a decongestant, stable state. I really believe that they are very effective for sudden cardiac death prevention.

Piña: It reverses remodeling.

Lam: Of course. That's how I try to simplify it in my mind. I know that there have been different permutations of the strategy on how to sequence. Honestly, isn't it just common sense and judging by the patient? The things that we look at in the patient are their blood pressure and heart rate, whether or not they're in atrial fibrillation or sinus rhythm, and then their potassium and creatinine. From that, just try to get them to target.

Piña: One of my approaches to patients is, depending upon how symptomatic they are, as you were saying, when I give them the RAAS blocker — angiotensin-converting enzyme (ACE) inhibitor, angiotensin receptor blocker (ARB), or ARNI — I tell them that they're going to feel better. They will feel better within a week. When I give them the beta-blocker, I don't say that.

Lam: No.

Piña: I tell them, “You may feel a little bit more tired, but it's going to go away. Stick with me.” I've always done the RAAS thing first, and like you said, maybe give them a beta-blocker just to get them started because I am also scared of sudden death. Our first defense against sudden death is a beta-blocker.

We started using SGLT2 inhibitors when I was still in New York, even before we knew that they worked in the nondiabetics. I thought, “Well, I'm going to send them back to their primary care to get their SGLT2 inhibitors because this is part of their diabetes work.” The patients were coming back without the SGLT2 inhibitors. They weren't being started.

I think Dr Braunwald has been telling us that we need to become diabetologists in a way, too. We started just giving it and managing it ourselves. These patients are on so many other drugs that are very complicated. We counted, and when they leave the hospital, they're on 13 drugs. How can you take 13 drugs in a day?

Lam: It's true. Ileana, I'm sure you do as I do, which is tell all my patients to bring it all in and really cut the crap. You have a patient with HFrEF struggling with blood pressure space. Why are they on amlodipine? I take that out.

Of course, there are choices that we make with medications. Beta-blockers, for example, are twice a day. You could do the short-acting and give it three times a day, but there are also the long-acting ones. We choose the long-acting ones if they're tolerating it. There are ways that we can help the patient.

I'd like to emphasize that, even as I said to simplify it into those four. It is very important to remember the backups. I have a backup list of five, including ivabradine if I've maxed out on beta-blockers and the heart rate is still not there.

Piña: That's not usual.

Lam: Right, but I have that in my back pocket. I do remember to look at the iron.

Piña: That's very important.

Lam: My patients have thanked me after giving intravenous iron to those who are very iron deficient.

Piña: They feel so much better, particularly the older women who have been dealing with iron deficiency for years and nobody has done anything.

Lam: Exactly. I also truly believe the data that we see with vericiguat. It got a class II recommendation in the new ESC guidelines, but remember, it was a large, positive study in a population with a large unmet need.

Piña: There was a very high event rate.

Lam: This was despite being on the standard medications: beta-blockers and MRAs. If they keep worsening, you really have to pull out the vericiguat card.

Piña: I agree with you. We are going to be looking at the women and the older patients in that trial. Do you think about sleep apnea as another option here?

Lam: I do. I have to say that when I was practicing in Rochester, Olmsted County, at Mayo Clinic, there were a couple more things that I would consider. I'm talking about obstructive sleep apnea with patients who are big. I don't see that as often in Singapore.

Piña: We see that often in the United States, where people are overweight.

Lam: Also, in African Americans, I would consider hydralazine and nitrates. Those are the things that you tuck behind. Now, I also consider vaccination.

Piña: Absolutely.

Lam: I have this little checklist of the other things. I start with the four, and then just have a checklist in my mind of other things that I should cover.

Piña: I like that because that gives our audience a sense of the very important things that you have to do regardless, and then all the other things that could modify it, especially this iron business.

How often have I seen with anemia or without anemia and the residents say to me, oh, that's chronic? Well, there is no such thing as chronic anemia of heart failure that I know of. You have to work it up. I've been starting to use the intravenous (IV) iron preparations. You're right, the way that the patients feel is amazing. We don't do that with any of our drugs.

Lam: Ileana, it's personal to me because I was iron deficient during my pregnancy.

Piña: Me too.

Lam: You remember how it felt.

Piña: It was terrible.

Lam: Imagine if you have heart failure on top of it.

Piña: You're exhausted and you're not eating enough to compensate, and the iron sulfate tablets do not get absorbed.

Lam: They actually make you feel sick.

Piña: Exactly. I think that we have so many tools now, but I like your initial posture, which is, let's look at the basic things that we have to get done. It's like a roadmap to give to the patients. I'm always thinking of easy ways to tell the patients what I want to do. I always do say to them, “You're not going to be on the same dose tomorrow as you are today. I'm going to keep changing these, but we'll give you updated lists.”

This shows how important it is to have the electronic health record be accurate with what the patient is on, and it often is not.

Lam: Ileana, you bring up such a good point about the communication and to moderate their expectations so that they're not feeling when we uptitrate them, “Oh no, what are you doing?”

Piña: They'll know right up front.

Lam: Exactly. Second, so that they know, for example, we're not putting them on an ACE inhibitor for their hypertension. I cannot tell you how many times that has happened, where they then go to the general practitioner who takes them off the ACE inhibitor because they're not hypertensive. I keep telling them it's not for hypertension.

Piña: Or the pharmacist is telling them it is a blood pressure drug.

Lam: Exactly, so we need to explain it.

Piña: Maybe all our societies should come up with a roadmap, literally, or a strategy that everybody could agree upon, and put it out there so that patients get the right care. This is especially important for our advanced practice nurses and pharmacists, who do a great job with uptitration of drugs. I think we'll leave it at that.

Carolyn, I hope you have a wonderful rest of the ESC. I hope you enjoy the rest of your summer. Big hug to that baby. Thanks again for spending time with me today.

Lam: Huge hugs. Thank you, Ileana.

Piña: This is Ileana Piña. I'm signing off. I hope this is helpful to you in your practice. Have a great day.

Ileana L. Piña, MD, MPH, is a heart failure and cardiac transplantation expert. She serves as an advisor/consultant to the FDA's Center for Devices and Radiological Health and has been a volunteer for the American Heart Association since 1982. Originally from Havana, Cuba, she is passionate about enrolling more women and minorities in clinical trials. She also enjoys cooking and taking spin classes.

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