Academic-industrial collaboration in the development of the first angiotensin receptor blocker: neprilysin inhibitor in the treatment of heart failure: Table 1

The important roles of the renin–angiotensin–aldosterone system (RAAS) and the natriuretic peptide system (NPS) in the regulation of arterial pressure and fluid volume in both health and disease have been well established for decades. Activation of the former causes vasoconstriction and sodium retention, while activation of the latter has opposing actions—vasodilatation, natriuresis, and diuresis. It is highly desirable to suppress the activity of the RAAS and to enhance the activity of the NPS in patients with heart failure, as well as in patients with hypertension. Considerable efforts to accomplish this both effectively and safely have recently met with success with the development of an angiotensin receptor blocker-neprilysin inhibitor (ARNi), likely the first of a new class of drugs. Cardiologists, many in the wider medical community, and millions of patients with heart failure were excited in March 2014 when Novartis announced that, on the advice of an independent Data Monitoring Committee, a large clinical trial with a new drug had been stopped because of overwhelming benefit.1 The results of the PARADIGM HF trial were presented at the European Society of Cardiology in August, 2014 and were published simultaneously in the New England Journal of Medicine.2 The editors of the Journal suggested that the results of the trial may lead to a ‘paradigm shift in heart failure therapy’.3 The U.S. Food and Drug Administration placed the drug (named Entresto) on a rapid track, and approved it for the treatment of heart failure with reduced ejection fraction on 7 July 2015, <16 months after cessation of the trial. The drug is now available in the USA and patients with heart failure have started to receive it. Regulatory agencies around the world are actively considering applications for its approval.