PracticeUpdate Cardiology June 2019

CONFERENCE COVERAGE 22

Updated Guidelines for theManagement of Heart Failure: NewMedications Interview with Clyde W. Yancy MD, MSc, MACC, FAHA, MACP, FHFSA by Aman Shah MD

Dr. Shah: I wanted to focus on some new classes of drugs that have or are becoming available for managing patients with heart failure. Could we start with ARNi (angiotensin receptor-neprilysin inhibitor)? What is this drug? What is this combination and how is it better? Dr. Yancy: Well, this is a brilliant conversation for us to have because, realize that the fact that there are new therapies available is more than just the availability of the therapies. It has enthused the population. It has captured the attention of providers. It’s made us understand that as a collective we can revisit heart failure and do something about it. New therapy number one: the ARNi compound. The combination of neprilysin inhibitor with an angioten- sin receptor antagonist. This odd combination has a unique pharmacology. It suppresses the activation of the renin-angiotensin-aldosterone system, which we believe and have evidence that it drives the progres- sion of heart failure, but it also promotes the positive influences of endogenous natriuretic peptides. Some- thing that escapes most practitioners is when you think about BNP (B-type natriuretic peptide), use the prototype, you think about it as a marker or biomarker. You forget that there’s a biology that is associated with that biomarker, and that biology is very favorable on the ventricle. It reduces fibrosis and influences a number of other metabolic and hormonal signals for the benefit of the patient who has left ventricular dys- function. So, the two together are synergistic and the trials demonstrate that.

There are lots of caveats about use that are easy to identify in published statements. Suffice to say, be aware of the blood pressure indicated in Class II and III. Any patient ever with a history of angioedema, the drugs are excluded. Never give the drugs con- comitantly with an ACE inhibitor, but as you get more comfortable utilizing the drugs, these things become second nature and can be inserted into protocols, but the big take-home message is that the correct application of the ARNi compound, not for every patient, but the correct application does save lives and improves quality of life. The other compound that is new and available for heart failure is not used very much but the evidence is very persuasive. In those patients that have a persistent resting heart rate above 80 despite being on a proper dose of beta-blockers and other evidence-based therapy, and it’s in sinus rhythm not atrial a-fibrillation, the addition of ivabradine, which uniquely identifies what some people call the funny channels or the I(f) channels, which only seem to influence heart rate and do nothing else, ends up being beneficial. Perhaps because by slowing heart rate we decrease myocardial energy consumption and maybe that’s a preservative strategy for ventricles that were affected with left ventricular dysfunction. So, we are aware that the data are valid, but the use has been limited because when beta- blockers are used correctly, most patients end up being below the heart rate of 80. Dr. Shah: Do we have longer-term data on actual out- comes of heart failure patients with this therapy? Dr. Yancy: So, we do have excellent data on outcomes. We have secondary outcomes even on mortality, but the primary outcome was a combination of hospital- izations and mortality, and it was really driven by the hospitalization component. We have excellent long- term data on the ARNi compound. We know that it is a verifiable signal that it does reduce mortality over and above that with which we see the ACE inhibitor. There’s a third compound that’s very important, and that’s the SGLT2 inhibitors. Not yet indicated for heart failure, but the enthusiasm in the community is really reaching a very high level because it seems to be able to reduce the first onset of heart failure in those with diabetes. And importantly, in those with diabe- tes and heart failure, it seems to have yet another benefit on reducing morbidity. For the first time now, trials are being done to test that drug class in the absence of diabetes, trying to uniquely capture this cardiovascular profile. If that, again, is replicated in a prospective, rigorous, randomized trial, boy, do we have another therapy. That would be great.

Dr. Yancy is Chief of Cardiology at Northwestern University, Feinberg School of Medicine and Associate Director of the Bluhm Cardiovascular Institute at Northwestern Memorial Hospital in Chicago, Illinois.

Go to www.practiceupdate.com/c/81069 to watch this interview with Dr. Yancy.

© ACC/Todd Buchanan 2019

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