The Combination of Valsartan and Sacubitril in the Treatment of Hypertension and Heart Failure – an Update

A novel antihypertensive drug, LCZ696 (Entresto®), has recently been introduced, which combines the action of an antagonist of the renin-angiotensin-aldosterone system (RAAS), effectively decreasing the blood pressure, with an inhibition of neprilysin, which is responsible for metabolizing natriuretic peptides exerting antihypertensive and antifibrotic effects. In this MiniReview, we describe the pharmacokinetics and pharmacodynamics, efficacy and side effects of the combined angiotensin receptor antagonist and neprilysin inhibitor LCZ696. We summarize the effect of LCZ696 treatment of patients suffering from hypertension and heart failure (HF) and further highlight the role of this new drug as a treatment option in the future. In the earlier stages of the treatment of patients with heart failure, LCZ696 was superior in lowering the blood pressure compared to olmesartan, while the effect on blood pressure at long-term treatment was comparable for the two drugs. The numbers of adverse effects were comparable. LCZ696 was superior to enalapril in reducing mortality, hospitalizations and HF symptoms. Adverse effects were reduced with a slower up-titrating regimen of 6 weeks. The current results are promising and suggest that LCZ696 will be a new candidate for first-line treatment of HF. However, it needs to be explored whether LCZ696 is safe in pregnant women, what are the effects of long-term LCZ696 treatment on survival and whether the antifibrotic effects can be of major benefit in, for example HF with preserved ejection fraction.