For treating patients with chronic heart failure, ACE inhibitors are usually the first port of call. But a new study claims an experimental drug called LCZ696 performs around 20% better than ACE inhibitors when it comes to reducing rates of hospitalizations and deaths due to chronic heart failure.
According to the Centers for Disease Control and Prevention (CDC), around 5.1 million people in the US have heart failure, and approximately half of these individuals will die within 5 years of diagnosis.
ACE (angiotensin-converting enzyme) inhibitors are currently a keystone treatment for chronic heart failure. These drugs stop an enzyme from producing angiotensin II – a substance that narrows the blood vessels and releases hormones that can increase blood pressure.
The new drug, developed by pharmaceutical company Novartis, consists of valsartan – an angiotensin receptor blocker (ARB) – and sacubitril, a substance that inhibits an enzyme called neprilysin, which in turn increases levels of peptides important for regulation of the cardiovascular system.
Co-principal investigator Dr. Milton Packer, of the Southwestern Medical Center at the University of Texas, says results from the team’s study – called PARADIGM-HF – fill him with confidence that the drug will eventually replace ACE inhibitors for the treatment of heart failure.
“The purpose of using a drug like this isn’t to make people feel better,” says Dr. Packer. “The major benefit is that the natural course of the disease is changed. I don’t think it changes the natural history of heart failure – I know it does.”
Results of the study, published in The New England Journal of Medicine, were recently presented at the European Society of Cardiology Congress 2014.
To reach their findings, the team compared the effectiveness of LCZ696 against an ACE inhibitor called enalapril in 8,442 patients with class II, III or IV heart failure and an ejection fraction of 40% or less.
The patients, who were from 1,043 sites across 47 countries, were randomized to receive either 200 mg of LCZ696 or 10 mg of enalapril twice daily between December 2009 and January 2013, in addition to other recommended treatment.
The team notes they included a “run-in period” in their study, which involved comparing the effects of LCZ696 against doses of enalapril that have been shown to reduce mortality among heart failure patients when compared with a placebo.
The researchers say because of the “overwhelming” benefits patients saw from LCZ696, the trial was stopped early. Compared with patients who took enalapril, those who took LCZ696 had a 16% reduced risk of all-cause mortality and a 20% reduced risk of cardiovascular mortality. They also had a 21% lower risk of hospitalization.
Furthermore, the researchers found that patients who took LCZ696 reported better toleration than those who took enalapril.
When measuring side effects among both groups, the team found that more patients who took LCZ696 experienced hypotension (low blood pressure) and non-serious swelling such as back pain, but fewer experienced renal impairment, anemia and cough.
Commenting on their findings, the researchers say:
“The magnitude of the beneficial effect of LCZ696, as compared with enalapril, on cardiovascular mortality was at least as large as that of long-term treatment with enalapril, as compared with placebo.
This robust finding provides strong evidence that combined inhibition of the angiotensin receptor and neprilysin is superior to inhibition of the renin-angiotensin system alone in patients with chronic heart failure.”
According to a report by Reuters, David Epstein, pharmaceuticals head of Novartis who funded the study, said the drug could be on the market by the third quarter of next year, although he did not state how much it would cost.
In an editorial linked to the study, Dr. Mariell Jessup, of Penn Medicine at the University of Pennsylvania Health System, says this study may represent a “new threshold of hope” for patients with heart failure.
“Efforts to design novel pharmacotherapies that exploit our growing knowledge of pathophysiological pathways are increasingly coming to the clinical arena,” she says.
“The dual (or more) action of such drugs may translate into even greater long-term survival for patients. The beneficial results seen in PARADIGM-HF may apply to a wide spectrum of patients, even those who are currently receiving the best possible therapy.”
Medical News Today recently reported on a study led by the Indiana University School of Medicine claiming a cardiac molecule – called Myheart – could prevent and treat heart failure.