Current Heart Failure Treatment Recommendations

Transcript: Deepak L. Bhatt, MD, MPH: Scott, perhaps, for the audience, you can just discuss the most recent ACC/AHA/HFSA [American College of Cardiology/American Heart Association/Heart Failure Society of America] guidelines for the management of heart failure. What changed compared with the prior version? What does our pretty diverse audience of primary care physicians, cardiologists, and other types of practitioners really need to know?

Scott David Solomon, MD: Deepak, if it’s OK, I’d also like to add to some of the things that were said earlier. When we talk about heart failure, obviously heart failure is a clinical syndrome, but we really have multiple phases of heart failure. Patients with heart failure with reduced ejection fraction are the ones who we can very easily understand and diagnose. It’s much more complicated when patients have heart failure with relatively preserved ejection fraction. We can talk at some point about what we mean by that. But I think it’s important to add that when a patient comes into the emergency room and is short of breath, has signs and symptoms of heart failure, and you do an echocardiogram and the heart is not contracting the way we would like it to, it’s easy to understand what’s going on with that patient. It’s much more complicated if the ejection fraction is 60%. So for the diagnosis in patients with heart failure with preserved ejection fraction, we sometimes really need to utilize natriuretic peptides as a way to ensure that these patients truly have this clinical syndrome of heart failure and not something else that is making them short of breath. Of course, as we started off talking about, there are other things that can cause patients to be short of breath.

Regarding the guidelines, for many years we’ve had the mainstay of therapy for patients with heart failure with reduced ejection fraction. So I’m going to start off talking about that because the guidelines are really distinct when it comes to HFrEF [heart failure with reduced ejection fraction] and HFpEF [heart failure with preserved ejection fraction]. When I say HFrEF, I’m primarily referring to heart failure with an ejection fraction of 40% or less. For many years now, the cornerstone, if you will, of guideline-directed therapy for HFrEF has been either an ACE [angiotensin-converting enzyme] inhibitor or an angiotensin receptor blocker [ARB] and beta blockers. These were, of course, based on clinical trials that have shown reduction in morbidity and mortality with these agents. So that’s basically the first step in heart failure management, as well as other things that we typically do in these patients.

Most patients with heart failure are treated, of course, with diuretics. I think it would be very unusual to have a heart failure patient who was not treated with a diuretic. After that, we have a number of different options that are outlined very nicely in the 2017 guidelines and the algorithms from the 2017 guidelines. These include aldosterone antagonists and mineralocorticoid-receptor antagonists like spironolactone or eplerenone. In the case of patients with severe class III-IV heart failure in the RALES trial, spironolactone was shown to reduce heart failure hospitalization and all-cause mortality. In the EMPHASIS-HF trial of patients with milder heart failure, eplerenone was shown to reduce morbidity and mortality. So it’s recommended to add these drugs to the cornerstone therapy, with the caveat that when you add a mineralocorticoid-receptor antagonist to an ACE inhibitor or an ARB, you increase the risk of hyperkalemia.

But in the last 5 years, we have 2 new pharmacologic therapies that can improve outcomes in patients with heart failure that we’ve added to our armamentarium. One of them is kind of a niche therapy called ivabradine. Ivabradine is a pure heart rate—reducing drug that has effectiveness for reducing heart failure hospitalization in patients with persistently elevated heart rate despite optimal beta blocker use. I call this a niche drug because it’s certainly not for everyone and is currently a class IIa indication in the guidelines.

The other therapy that we have, of course, is sacubitril/valsartan, which is an ARNI, or an angiotensin receptor—neprilysin inhibitor. This is essentially a combination of an angiotensin receptor blocker and a neprilysin inhibitor. Neprilysin is an enzyme that breaks down the biologically active natriuretic peptides and a host of other vasoactive substances. So by giving this drug, you actually inhibit the renin-angiotensin system and also augment the endogenous vasoactive peptide systems. In a head-to-head trial comparing the angiotensin receptor–neprilysin inhibitor sacubitril/valsartan with enalapril, which has been thought to be the gold standard in heart failure with reduced ejection fraction, we saw a 20% overall reduction in cardiovascular death, heart failure hospitalization, and a 16% reduction in all-cause mortality. Based on that trial—the PARADIGM-HF trial—ARNIs are now considered class I in the treatment of heart failure with reduced ejection fraction. The recommendation is to switch from ACE inhibitors and ARBs to the ARNI in appropriate patients.

I don’t want to forget to mention another pharmacologic therapy that has been tested in African Americans. This is the combination of hydralazine and isosorbide dinitrate in the A-HeFT trial. There is some evidence that on top of standard-of-care therapy, this therapy will also provide benefit.

Finally, I think it’s important to recognize that there are nonpharmacologic treatments available for appropriate patients with heart failure. Clearly in patients with ejection fractions that are relatively low—35% or below—ICD [implantable cardioverter-defibrillator] therapy can prevent sudden death. And in patients who have evidence of low ejection fraction—again, 35% or below—left bundle branch block, and a wide QRS complex, there’s evidence that demonstrates these patients will benefit from cardiac resynchronization therapy.

Deepak L. Bhatt, MD, MPH: That was pretty much everything you need to know about heart failure in a nutshell. That was fantastic.

Transcript Edited for Clarity