A new experimental drug could help many people with a certain kind of heart failure live longer, better lives, according to a large research trial published Sept. 11 in the New England Journal of Medicine.
About 5.7 million Americans are living with heart failure, when the heart doesn’t pump as well as it should. The weakened heart can’t supply the cells with enough blood, causing fatigue and shortness of breath. This can make everyday activities like walking or carrying groceries difficult.
“At long last it looks like we have a blockbuster for heart failure with reduced ejection fraction,” said Mariell Jessup, M.D., professor of medicine and medical director of the Heart and Vascular Center at the Hospital of the University of Pennsylvania in Philadelphia.
In the five-year study PARADIGM-HF, Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure Trial, researchers assigned 8,442 people who had mild to moderate heart failure and an ejection fraction of 40 percent or less to receive LCZ696, an experimental drug, or enalapril, a drug commonly used to treat heart failure. Ejection fraction is a measurement of heart function that indicates heart failure when it’s 50 percent or less.
The study is among the top scientific cardiovascular developments in 2014, as determined by the American Heart Association.
LCZ696 reduced deaths from cardiovascular disease by 20 percent and lowered deaths from all causes by 15 percent compared to enalapril. It also lowered the risk of hospitalization by 21 percent and resulted in a better quality of life with few side effects, according to study authors.
Although the heart failure patients studied were clinically stable, Jessup said they still face serious health consequences, including getting worse and being hospitalized, with 7 to 8 percent dying.
“I hope we can bring the drug to market quickly,” said Jessup, a former president of the American Heart Association. “We have people who we think are stable who die at an unacceptable rate.”
This was the first time researchers combined the two types of drugs in LCZ696 — a neprilysin inhibitor and an angiotensin receptor antagonist, or ARB — to treat heart failure.
Neprilysin is an enzyme that breaks down natural substances in the body that open narrowed arteries. Limiting the effect of neprilysin could increase the effect of these substances and improve artery opening.
The new drug was compared to enalapril, an angiotensin-converting enzyme inhibitor, or ACE inhibitor, commonly used to treat heart failure.
Both ACE inhibitors and ARBs limit the hormone that causes the body to retain sodium and narrow blood vessels.
More than a decade ago, researchers created a drug combining a neprilysin inhibitor with an ACE inhibitor, but it led to potentially life-threatening skin swelling.
“Almost everyone who is currently on an [ACE] inhibitor could be a candidate for this drug,” said Milton Packer, M.D., study co-author. This study represents, “a sea change in treatment for the vast majority of people who have heart failure and a reduced ejection fraction.”
An additional analysis, presented at the American Heart Association’s Scientific Sessions in November, looked at whether heart failure patients living with the disease maintained their stability for longer periods of time.
After the first trial was published, “People kept on asking us, ‘what happened to the people who were alive? Did they feel better? Did they do better? Or were they just the same, or were there just more of them?’” said Packer, who is a professor and chair of the Department of Clinical Sciences at the University of Texas Southwest Medical Center in Dallas, Texas.
Researchers studied worsening symptoms, including physical symptoms, quality of life, emergency room and hospital visits, aggressive medical therapy and inpatient or outpatient care. In every category, patients did better on LCZ than on enalapril, and the arguments for switching patients to LCZ are “extraordinarily powerful,” Packer said.
“Yes, your patients may be doing well, but they’re still going to die, so if you switch them, not only will they live longer, but will deteriorate less rapidly even when they’re alive,” he said. “If price and cost are a factor, it may give them pause. But it won’t be the data that gives them pause.”
Read other top 2014 research: Top Cardiovascular Disease Research Advances of 2014 Summary.
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