The approval of the first angiotensin-receptor/neprilysin inhibitor (ARNI) valsartan/sacubitril by the US Food and Drug Administration (FDA) for the treatment of heart failure with reduced ejection fraction (HFrEF) offers a new hope for patients, fueling a renewed excitement among cardiologists.

Dr. Clyde Yancy, cardiologist from the Northwestern University in Chicago, Illinois, US described the approval as “a new day in heart failure.” The approval came after an expedited review – reserved by the FDA for novel drugs believed to fill an unmet medical need – on the heels of the PARADIGM-HF* trial results last year which showed that valsartan/sacubitril (formerly called LCZ696) significantly reduced the risk of cardiovascular (CV) death and hospitalization for HF compared with the ACE inhibitor enalapril. [N Engl J Med 2014;371:993-1004]

The approval was the quickest for a CV drug in a long time and some experts are optimistic valsartan/sacubitril, given in the right patients, could replace ACE inhibitors, which are the standard of care in HF therapy.

Yancy, however, said more discussions are still needed. “We aren’t ready to offer [valsartan/sacubitril] carte blanche to everyone who comes to our offices.”

PARADIGM-HF was halted early in March, after a median follow-up of 27 months, because patients taking LCZ696 achieved a statistically significant reduction in CV deaths and HF hospitalizations despite being on beta-blockers and a diuretic. Cardiologists considered this a major step forward since only a few therapies have shown mortality reduction in HF or in other CV conditions.

Given the increasing morbidity in HF, hospitalizations, and cost of care, any new therapy that has an added benefit to – or is better than – ACE inhibitors is a potential game-changer, said Professor Carolyn Lam, senior consultant, National Heart Centre, Singapore and associate professor with the Duke-NUS Cardiovascular Academic Clinical Program. However, she added clinicians should approach this development with “cautious optimism.”

“The PARADIGM-HF trial is among the best phase III trials we have in the HF world, and results appear robust. However, I do not expect doctors will now replace ACE inhibitors with LCZ696 in all their stable patients,” said Lam. “As with all new agents, ‘real world’ or phase IV data are needed to inform clinicians as to which HF patients would be most likely to achieve benefit with the least risk.”

The FDA said valsartan/sacubitril should not be used with any ACE inhibitor because of increased risk of angioedema.