Entresto May Reduce Heart Failure-Related Adverse Events

Novartis recently announced clinical trial findings that show Entresto (sacubitril/valsartan) reduces adverse events in patients with heart failure.

Investigators discovered that compared with enalapril, Entresto was able to reduce the risk of heart failure hospitalizations and deaths following hospitalization among patients with heart failure with reduced ejection fraction (HFrEF).

The PARADIGM-HF clinical trial is the largest to be conducted in patients with heart failure to date. These new findings will be presented at the American Heart Association Scientific Sessions 2016.

“In PARADIGM-HF, about one-third of heart failure patients with a first event experienced subsequent events, underscoring the substantial risks faced by patients with this life-threatening condition,” said Professor John McMurray of the University of Glasgow, and co-principal investigator for PARADIGM-HF. “The fact that sacubitril/valsartan not only reduced the risk of a first event, but also of repeat events, which are at least as serious and costly, and all too common - is highly significant and reinforces why this medicine is now guideline-directed therapy.”

Investigators analyzed data regarding the amount of heart failure hospitalizations and cardiovascular deaths that occurred during the clinical trial. During the 27-month follow-up period, approximately 3181 primary endpoint events were observed, with 1251 deaths occurring. One-third of patients who experienced a primary event also experienced a repeat event.

According to Novartis, Entresto reduced the risk of first-time and repeat events by 20% to 24% compared with enalapril. These findings are consistent with the original findings from the clinical trial, which demonstrated a 20% risk reduction compared with enalapril.

Additional post-hoc analyses showed that Entresto was also associated with fewer dose increases of diuretics and more dose reductions compared with enalapril. Patients who were taking Entresto plus a mineralocorticoid receptor antagonist had a lower risk of developing severe hyperkalemia compared with enalapril plus an MRA, according to Novartis.

Entresto was also seen to provide clinical benefit to patients with severe heart failure symptoms.

Compared with other heart medications, Entresto can provide additional benefits since it combines a neprilysin inhibitor (sacubitril) and an angiotensin receptor blocker (valsartan). The drug works by magnifying the neurohoromonal systems and inhibiting overactive renin0angiotensin-aldosterone system, which can be harmful.

Entresto is indicated in patients who have heart failure with systolic dysfunction in the United States, and is indicated for treatment in patients with HFrEF.

“These analyses further support our knowledge that Entresto can keep many heart failure patients with reduced ejection fraction alive and out of the hospital for longer," said Vas Narasimhan, global head of Development and Chief Medical Officer for Novartis. “As we continue to analyze the results of the PARADIGM-HF study, we become more and more confident in the benefit that Entresto can bring to patients and to potentially reducing costs of care to healthcare systems.”