What Is the Future Role of ACE Inhibitors?

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The HCPLive Peer Exchange: Advances in Heart Failure Management features expert opinion and analysis from leading physician specialists on the latest developments in heart failure research, diagnosis, and management.

This Peer Exchange is moderated by Peter Salgo, MD, professor of medicine and anesthesiology at Columbia University and an associate director of surgical intensive care at the New York-Presbyterian Hospital in New York City.

The panelists are:

• Michael Felker, MD, MHS, Professor of Medicine, Chief of the Heart Failure Section, Director of the Heart Center Clinical Research Unit, and Director of the Advanced Heart Failure Fellowship at Duke University School of Medicine
• Jim Januzzi, MD, Roman W. DeSanctis Endowed Distinguished Clinical Scholar in Medicine at Massachusetts General Hospital and Hutter Professor of Medicine at Harvard Medical School
• Christian Schulze, MD, PhD, Associate Professor of Medicine, Division of Cardiology at Columbia University Medical Center, and Director of Research for the Center of Advanced Cardiac Care at Columbia University Medical Center

This segment begins with a brief discussion on the reasons for physician entropy in heart failure treatment before continuing on to discuss the future implications of ACE inhibitors in light of the PARADIGM-HF trial.

The issue of physician entropy may be related to the clear dose-responsiveness of all of the available heart failure medications. Januzzi says there are many unanswered questions regarding dosing, such as: “How do we uptitrate these drugs in a safe, methodical fashion? What’s the stopping point? Do we keep going even above the targets that are articulated in the guidelines if the patient can continue tolerating these doses?”

When managing heart failure in patients with reduced ejection fraction, “it’s reasonable to expect that once LCZ696 is approved, it will be put ahead of ACE inhibitors in the guidelines,” says Januzzi. And this could even expand to the preserved ejection fraction population as well once the PARAGON data are available. However, he says, “For the time being, what I would tell my patients is that this drug is not necessarily for everyone.”

In PARADIGM-HF, “a substantial number of patients did not make it through the run-in period because of hypotension, typically.” Therefore, not all patients can tolerate “aggressive uptitration of LCZ696.” It remains to be seen whether these patients will be given lower doses of LCZ696 or if they will be “reverted back to ACE inhibitors as their vasodilator of choice.”

LCZ696, while very successful in the PARADIGM-HF trial, is somewhat limited to the low ejection fraction heart failure population, says Felker. ACE inhibitors are used for a wide range of indications, such as hypertension, progression of chronic kidney disease, and vascular risk, but LCZ696 has not been studied in any of these areas to date. “I’m sure moving forward, it’s very likely to be studied in other relevant conditions, but I think ACE inhibitors are going to be around for a while,” he says.