10 Things to Know About New Heart Failure Med Entresto

Dr. Sharon Orrange
Dr. Orrange is an Associate Professor of Clinical Medicine in the Division of Geriatric, Hospitalist and General Internal Medicine at the Keck School of Medicine of USC.
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A new combination pill is available that will save lives from heart failure. Entresto has been shown to reduce hospitalizations and save lives from heart failure in certain patients. Entresto is a promising pill that is a mixture of old and new—here’s what you need to know.

  1. Entresto, just approved in July, is a mixture of two medications: valsartan (generic Diovan) an angiotensin receptor blocker (ARB), and sacubitril which is a neprilysin inhibitor.
  2. What’s new about it? Sacubitril is the newer half of Entresto. Bear with me for some details. Inhibiting neprilysin raises levels of several peptides (small proteins) that have beneficial effects on blood flow in patients with HF. Remember that low cardiac output (low blood flow because the heart can’t squeeze well) is the main problem in heart failure. Saccubitril, the neprilysin inhibitor in Entresto, improves blood flow to the kidneys and improves removal of fluid (diuresis), among other things.
  3. Does it work? Yes. Entresto reduced mortality and morbidity compared to ACE inhibitors like lisinopril when used in combination with other standard heart failure drugs. So, folks on Entresto had fewer deaths and hospitalizations from heart failure than those on ACE inhibitors or ARBs alone.
  4. Why does it work? Well, controlling the hormone system that regulates blood pressure is key in the treatment of heart failure patients—and that’s what the valsartan half of Entresto does. The other benefit comes from sacubitril, mentioned above.
  5. Who will use Entresto? Current recommendations will change once Entresto has been around longer, but right now it’s recommended for people with heart failure and a reduced ejection fraction (forward squeeze of the heart) of < 40%, or for people who have been hospitalized for heart failure in the past 12 months.
  6. Entresto is used in place of which other drugs? It is recommended in place of an ACE inhibitor (lisinopril, enalapril, benazepril) or an angiotensin receptor blocker (ARB) which include losartan and valsartan. Remember, Entresto contains valsartan—the combination is what makes it more effective.
  7. Changing tide. As we get more experience with Entresto, it will likely be recommended for a more people, across a broader range.
  8. Are there downsides to Entresto? A washout period of 36 hours is required prior to starting Entresto. This means you will need to stop taking all ACE inhibitors or ARBs for 36 hours prior to starting Entresto. It’s also new, so there doctors and patients alike have limited experience with it. Finally, as a new drug, the cost will be high.
  9. Will Entresto replace other heart failure medications like ACE inhibitors? Maybe, but because it’s so new there are no guidelines that have addressed the use of Entresto as an alternative to ACE inhibitor or ARB therapy alone. Stay tuned. [Update August 2016: Guidelines have been updated to recommend Entresto as an alternative to ACE inhibitors or ARBs.]
  10. How is Entresto taken? Your doctor will decide on your starting dose, and help you increase the dose as you can tolerate it. Generally speaking, the starting dose is a 49 mg/51 mg tablet taken twice daily.

Dr O.

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