Heart Failure Guideline Updates

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The MD Magazine Peer Exchange “Managing Heart Failure Today: Current Best Practices and New Treatment Options” features a panel of physician experts discussing key factors to consider when making treatment decisions for patients with heart failure and their own clinical experiences with recently approved medications for the treatment of heart failure.

This Peer Exchange is moderated by Peter Salgo, MD, professor of medicine and anesthesiology at Columbia University College of Physicians and Surgeons, and an associate director of Surgical Intensive Care at New York-Presbyterian Hospital.

The panelists are:

• Michael Felker, MD, MHS, professor of medicine and chief of the Heart Failure Section at Duke University School of Medicine, in Durham, NC
• Milton Packer, MD, Distinguished Scholar in Cardiovascular Science, Baylor Heart and Vascular Hospital, Baylor University Medical Center, in Dallas, TX
• Scott Solomon, MD, Senior Physician and director of Non-Invasive Cardiology at Brigham and Women’s Hospital, and Edward D. Frohlich Distinguished Chair and professor of medicine at Harvard Medical School, in Boston, MA
• John R. Teerlink, MD, director of Heart Failure at San Francisco Veterans Affairs Medical Center and professor of medicine at UCSF in San Francisco, CA

Peter Salgo, MD: Okay, so that brings us to guidelines. Every specialty has got guidelines. Cardiology is no exception. We have the most recent ACCF (American College of Cardiology Foundation) [guidelines] and the AHA (American Heart Association) heart failure guidelines. Are people following them? If so, what’s changed? Are they following the new ones?

John R. Teerlink, MD: The 2013 ACC/AHA (American College of Cardiology/American Heart Association) guidelines were the most recent complete guidelines presented. Those guidelines gave a great evidence base for what we should be doing, and no, people are not doing them. So, we know that our physicians are not getting patients on the right medicines. They’re not getting them on the right doses, and they’re not following up on those medicines even when they get them on them.

One example is the mineralocorticoid receptor antagonists, or MRAs—so, spironolactone, eplerenone. We know that these agents are tremendous for improving survival. Yet, when they were first implemented, people said, “Okay, these are great, we’ll start patients on spironolactone,” and then they never checked a potassium level. Whereas in the trials, these potassium [levels] were very carefully [monitored], and in the guidelines, they were told that these specific laboratory recommendations [required] follow up. So, the guidelines are very convincing, and if physicians can actually follow them, we believe that they’ll definitely be able to improve the health of our heart failure patients.

Peter Salgo, MD: Okay. Anything new? What’s changed?

Milton Packer, MD: It doesn’t matter what’s new. It’s a matter of, again, making sure that people understand the framework. If you have certain types of cancer and they are serious, and they have spread, what would be reasonably typical is that you would go to someone and they would prescribe, let’s say, 3 drugs all at once, at a specific dose for a specific duration of time. Because we know that those drugs, used at that dose for that duration of time, make a difference in terms of prevention of cancer recurrence and prolongation of life. That’s exactly what we should be doing in heart failure.

Peter Salgo, MD: What you’re telling me is that people aren’t following [the guidelines]?

Milton Packer, MD: Okay, but don’t worry about the guidelines.

Peter Salgo, MD: Oh, I worry about guidelines all the time.

Milton Packer, MD: Well, don’t worry about the guidelines. The guidelines provide a summary of clinical trial evidence.

Peter Salgo, MD: Okay.

Milton Packer, MD: They provide a very reasonable summary of clinical trial evidence. But, it would not make a lot of sense to read part of the guideline and ignore another part of the guideline.

Peter Salgo, MD: Exactly my point.

Milton Packer, MD: The goal here is not to sit and read the document. The goal is to understand what actually needs to be done and [determine] how it needs to be accomplished in patients with heart failure.

Peter Salgo, MD: But shouldn’t step one be at least knowing what the guidelines are?

Scott Solomon, MD: You know, we’re talking about the signals, the pathways. We treat heart failure, and, specifically, we’re talking about heart failure with reduced ejection fraction here. Almost everybody who has heart failure gets treated with diuretics because it makes them feel better. There’s not a lot of good scientific evidence for that, but there doesn’t have to be for many of the things that we do.

And getting back to this issue of the signal pathways, the neurohormonal systems that are activated, we have to block 2 important systems: the renin-angiotensin aldosterone system and the sympathetic nervous system. We do the first with ACE (angiotensin-converting enzyme) inhibitors, angiotensin receptor blockers (ARBs), mineralocorticoid receptor antagonists, and now a new class of agents: the angiotensin receptor/neprilysin inhibitors (ARNIs). We do the second with beta blockers, primarily. This is really the cornerstone of pharmacologic treatments of heart failure.

John R. Teerlink, MD: And those things have been incorporated into the newest guidelines.

John R. Teerlink, MD: Right. So, in 2016, the ACC and AHA did an update—[but] they’re not a full guideline. The distinction I wanted to make is that these are just an update. They were specifically designed to address 2 new agents that have been approved and [have] emerged. One is the angiotensin receptor blocker/neprilysin inhibitor, which is variously called valsartan, sacubitril, LCZ696, or a trade name of Entresto. I’ll just use LCZ696, or LCZ, because it’s shorter.

And the ACC/AHA update gave a level 1 recommendation, saying that ACE inhibitors, ARBs, or now the ARNIs should be given to patients with reduced ejection fraction to improve morbidity and mortality—that was the first statement. That was a very potent statement [putting] the ARNIs on the same level as an ACE inhibitor and an ARB in terms of their ability to improve those kind of outcomes.

The second class 1 recommendation, by the guidelines, is that in patients who were on stable doses of ACE inhibitors or ARBs, in the appropriate patients, they should have the ARNI substituted for those 2 agents. This is based on the PARADIGM-HF trial.

Peter Salgo, MD: This is big news.

John R. Teerlink, MD: This is huge news.

Peter Salgo, MD: This is a big difference.

John R. Teerlink, MD: This is the first time, recently, that we’ve been able to effectively replace a therapy, which is the cornerstone of our therapies—an ACE inhibitor or an ARB—with a new therapy. But these recommendations continue to say there are some cautions. So, there are class 3 recommendations [saying], “You’re going to cause harm.”

One of those things is you don’t want to start this ARNI within 36 hours of having a patient who has been on an ACE inhibitor because of the concern of initiating angioedema. Then, finally, the other aspect is that for patients who’ve had angioedema in the past, they should not be started, probably, on an ARNI.