New Drug Options for Heart Failure

Health Writer
Medically Reviewed

For many people with chronic heart failure, two recently introduced drugs might help cut the risk of a hospital stay and possibly prolong their lives.

Both drugs—sacubitril/valsartan (Entresto) and ivabradine (Corlanor)—received major endorsements in the latest heart failure treatment guidelines from the American College of Cardiology (ACC), the American Heart Association (AHA), and the Heart Failure Society of America (HFSA).

In fact, Entresto can now be considered a first-choice therapy, ahead of the ACE inhibitors that have long been the cornerstone of heart failure treatment.

The drugs were approved by the Food and Drug Administration and came to market in 2015, making them the first new medications approved for heart failure in nearly a decade.

Then followed the ACC/AHA/HFSA updated guidelines, published in Circulation in May 2016, which say that when used judiciously, the medications represent a “milestone” in the evolution of care for patients with heart failure.

However, neither drug has been used in the real world long enough to know how it will ultimately affect heart failure patients’ outlook. But based on clinical trials, the hope is that those drugs will make a significant difference for some people.

More living with heart failure

More than 5 million Americans have heart failure, and that number will only keep growing. The American Heart Association predicts that nearly 8 million Americans will be living with heart failure by 2030—largely because the population is aging.

And while medicine has made strides in managing the disease, heart failure remains a major cause of hospitalization and death.

Each year, heart failure complications send about 1 million Americans to the hospital, and the disease is a leading cause of hospital stays for people age 65 and up.

What’s more, a recent government study found that after a dozen years of falling, the national death rate from heart failure began creeping up after 2012. By 2014, it stood at 84 deaths per 100,000 people.

There is a long list of drugs that, along with lifestyle measures, can ease heart failure symptoms and reduce strain on the heart. However, the disease eventually progresses, creating a need for new treatment options.


Entresto is a twice-a-day pill that combines an old drug, valsartan, with a new one, sacubitril. It was quickly welcomed as a breakthrough treatment by many cardiologists, based on its performance in a clinical trial published in The New England Journal of Medicine.

In that study, Entresto prevented more hospitalizations and deaths than the ACE inhibitor enalapril (Vasotec)—one of the mainstay medications for heart failure.

The trial included more than 8,400 patients with moderate to more severe heart failure, plus a reduced ejection fraction, which means that with each heartbeat, the heart’s lower chambers were pumping out much less blood than normal.

The patients were randomly assigned to take twice-daily doses of either Entresto or enalapril, in addition to other heart failure medications that their doctors prescribed. The trial was stopped early, after patients had typically been followed for just over two years, because it had become clear that the new drug had greater benefits.

At that point, just under 20 percent of the ACE inhibitor patients had died, versus 17 percent of Entresto patients. The drug specifically cut the risk of hospitalization for heart failure and the risk of death from cardiovascular causes by about 20 percent, compared with enalapril.

• How does it work? Entresto is the first in a new class of medications that target an enzyme called neprilysin. It has two components: valsartan (the active ingredient in the heart failure drug Diovan) and sacubitril, a new drug that inhibits neprilysin. It is believed that in doing so, sacubitril enhances neurohormones that dilate the blood vessels and ease the heart’s workload.

• Is it for you? Officially, Entresto is approved for people with class II, III, or IV heart failure, with a reduced ejection fraction. That translates to a significant portion of Americans with heart failure—about 2.2 million people, according to estimates from Novartis, the drug’s maker.

Under the new treatment guidelines, Entresto can be considered a first-choice treatment, and used instead of an ACE inhibitor or an angiotensin II receptor blocker. If you are already on one of those drugs and still having heart failure symptoms, your doctor might recommend switching to Entresto.

The drug is not for everyone, however. It has side effects, often related to blood vessel dilation.

In the trial, side effects included low blood pressure that caused symptoms such as dizziness; high potassium levels in the blood, which can raise the risk of a heart arrhythmia; signs of kidney dysfunction; and angioedema—swelling under the skin, often around the eyes and lips.

Low blood pressure and angioedema were the only problems that affected Entresto patients more often than ACE inhibitor patients. But because angioedema can be life-threatening if it interferes with breathing, some caution is in order: You should not take Entresto if you’ve ever had angioedema, and the drug cannot be used with an ACE inhibitor because the combination raises the risk of angioedema.

There’s also a practical consideration: the price tag. Entresto costs about $4,500 a year, whereas ACE inhibitors are available in inexpensive generic versions. However, Medicare does cover Entresto, as do many private insurers.


Corlanor (ivabradine) did not make as big a splash as Entresto—partly because study results were mixed.

It’s also targeted toward a more limited group of heart failure patients: those whose resting heart rate remains persistently high (70 beats per minute or higher) despite treatment with beta-blockers. Still, for those individuals, Corlanor may reduce the likelihood of a hospital stay.

The drug’s approval was based on a clinical trial of 6,500 patients who had been hospitalized in the past year for heart failure and had a stubbornly high resting heart rate (at least 70 beats per minute).

Over roughly two years, patients given Corlanor along with standard therapy were 26 percent less likely to be hospitalized for worsening heart failure, versus patients given a placebo.

Corlanor comes in tablet form and works by slowing the heart rate, which helps lessen strain on the heart. That’s also the source of its most common side effect: an abnormally slow heart rate.

About 10 percent of patients in the clinical trial developed a low heart rate, while anywhere from 2 to 9 percent developed high blood pressure, atrial fibrillation, or temporary vision disturbances.

• Is it for you? Corlanor might benefit people with heart failure symptoms and a high resting heart rate despite treatment with the highest tolerable dose of a beta-blocker. Keep in mind, though, that concerns have been raised about Corlanor’s heart rate effects.

In Europe, where the drug is also used to treat angina, regulators made recommendations in 2014 that were aimed at reducing angina patients’ risk of dangerously slow heart rates. They stressed that the drug should only be used when a patient’s resting heart rate is at least 70 beats per minute.

That warning was based on a large trial of patients with angina, not heart failure. But it’s important for anyone taking Corlanor to be aware of possible signs that the drug is causing problems—including dizziness, fatigue, a racing heartbeat, or chest pressure.

And like Entresto, there’s a hefty price tag: Corlanor costs about $4,500 per year, which may be covered by some insurance plans.

The bottom line

New options are available that might help keep you out of the hospital or prolong your life. But it’s important to talk to your doctor about an overall treatment plan—the mix of lifestyle changes and medications—that could both lengthen your life and improve the quality of it.

Learn more about how to reduce your risk of heart disease.