Heart Failure: a Promising New Drug on the Horizon

Francis McNary, a retired textbook salesman, used to practically live on an airplane. Now, at 82, McNary hasn’t been on an airplane in five years. “I wouldn’t get on one if you paid me,” he says.

The reason is that McNary suffers from heart failure, and even minimal physical activity causes shortness of breath and a potential buildup of fluid in his body — specifically in his ankles, legs and now, his abdomen. “It’s been a slow, gradual deterioration of my faculties,” McNary says, adding that he’s been hospitalized about 10 times since suffering a heart attack in 1988, which led to heart failure.

But McNary is optimistic about a new treatment on the horizon called LCZ696, which in an international study showed improved survival in previously treated heart failure patients. The PARADIGM-HF study, published in August in the New England Journal of Medicine, found that the drug reduced patients’ risk of death and hospitalization from heart failure, more so than the standard treatment of enalapril, an ACE inhibitor, which stands for angiotensin converting enzyme. ACE inhibitors help relax blood vessels and lower patients’ blood pressure.

As a class of drugs, ACE inhibitors marked the first real improvement in treating patients with heart failure when they came on board in the late 1980s, says Orly Vardeny, an associate professor of pharmacy and medicine at the University of Wisconsin–Madison. “It was the first thing to reduce death by about 15 percent,” Vardeny says. That was a huge advance, so any drugs that came later, she adds, “had to be tested on top of ACE inhibitors.”

Drug’s Dual Mechanism of Action

LCZ696 is the first such drug to mark another significant improvement in heart failure treatments. The drug acts as both an angiotensin receptor blocker and utilizes a neprilysin inhibitor, which limits the hormones that cause blood vessel constriction.

Heart failure is caused by the inability of the heart to pump blood efficiently to oxygenate various organs throughout the body. People with the condition also release a hormone called aldosterone, which causes the body to retain fluid. The new drug helps combat both conditions, says Scott Solomon, a professor of medicine at Harvard Medical School and one of the trial investigators.

“We’re extraordinarily excited about this new therapy,” Solomon says. “It’s our first opportunity to make a dent in people living with heart failure.” Solomon and colleagues studied the drug in a trial with more than 8,400 patients in 40 countries throughout the world. Some were given LCZ696, and others took enalapril, an ACE inhibitor and the standard therapy for heart failure. Patients who received the new drug had a 20 percent lower risk of dying from heart failure or another cardiovascular condition, a 20 percent lower risk of being hospitalized with heart failureand a 16 percent lower risk of death from any cause. These results, Solomon says, are “extremely statistically significant. This has probably been the most successful trial in heart failure in a decade.”

The trial, which lasted just over four years, was so successful that it was stopped early, and the drug is on the fast track to Food and Drug Administration approval, which is expected later this year. “I’m cautiously optimistic that this is going to be a meaningful drug and an addition to our regimen,” says Mariell Jessup, a professor of medicine at the Perelman School of Medicine at the University of Pennsylvania and the immediate former president of the American Heart Association.

Prolonging Lives

Although heart failure typically strikes people age 65 and older, the trial enrolled participants from various age groups and included both men and women. “There was tremendous consistency in the benefit of the drug for different patient characteristics,” Solomon says.

Heart failure is still the leading cause of cardiovascular death in the U.S., and while it might be some time before LCZ696 changes that situation, the drug should at least allow people to live longer and better lives, Vardeny says. She adds that the success of the drug begs the question of whether newly diagnosed heart failure patients should also take this drug. “Should this drug be first-line therapy because it was shown to be so much better?” Vardeny says. “We just don’t have data for that yet. That question will be answered soon.”

Jessup adds that dose toleration might be another issue to study, since the study only looked at one dose. She and Solomon also anticipate that the success of LCZ696 will encourage other pharmaceutical companies to develop similar drugs. “I think there were many pharmaceutical companies that were getting discouraged” by the lack of progress in heart failure drugs, Jessup says. “This shows it can be done.”

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Sasha Perkins

Administrative Assistant and Journalist at the Pluto Daily since 2012.