A drug developed by Novartis for management of patients with heart failure – Entresto (sacubitril/valsartan) – also termed LCZ696, was approved for clinical use by the FDA.
LCZ696 was assessed in the PARADIGM-HF trial (1), where 4,187 patients were randomized to LCZ696 and 4,212 to enalapril. LCZ696 was given at a dose of 200 mg twice daily and was compared against the established ACE inhibitor enalapril (10 mg twice daily). LCZ696 was superior to enalapril regarding all cause mortality (711 patients versus 835, P<0.001), hospitalization for heart failure (P<0.001) and heart failure-related symptoms or disability (P=0.001). The new agent has side effects that should be taken into account when prescribed to heart failure patients. Main side effects include hyperkalemia, renal function impairment and hypotension. This new agent expands the current pharmacological armamentarium for managing heart failure patients and is likely to be well received by physicians working in the heart failure field.
The new drug LCZ696 consisting of the molecules of valsartan and sacubitril bound together in a new chemical entity that dissolves into the gastro-intestinal tract has shown to be superior to low-medium dose of Enalapril in predominantly NYHA class II patients with Heart Failure included in the PARADIGM trial. The clever design of the study, that included a run in phase with Enalapril, enabled investigators to reduce the possibility of angioedema and the inclusion of patients with elevated natriuretic peptides at baseline enriched the event rate of the patient population. Therefore, the results of the PARADIGM study cannot be translated to stable patients with heart failure, to those with low levels of natriuretic peptides, advanced stages of the disease, those who are in the early phase after hospitalisation and those who are naïve to ACE-inhibition. The risk of angioedema cannot be overlooked and therefore only patients who have safely received ACE-inhibitors in the past can be reasonably treated, at least in the initial phase of drug marketing, with LCZ696.