Novel blood pressure agent shows promise

Natriuretic peptides have a number of beneficial vascular effects: vasodilator and natriuretic properties, reduced sympathetic drive, antiproliferative effects, and inhibition of the renin–angiotensin–aldosterone (RAAS) system. Inhibition of neprilysin (neutral endopeptidase 24.11) leads to an increase in natriuretic peptide levels, but on its own this mechanism does not lead to a clinically significant decrease in blood pressure. However, concomitant administration of an inhibitor of the RAAS system could potentially eliminate this problem, thus a novel dual-acting neprilysin and RASS inhibitor labelled LCZ696 was investigated in this study.

One-thousand, two-hundred and fifteen patients completed 8 weeks of treatment with LCZ696. All patients had mild-to-moderate hypertension and were randomly assigned to LCZ696 at various doses, valsartan, a neprilysin inhibitor on its own or placebo. Compared to treatment with valsartan alone, patients taking LCZ696 showed significantly greater reductions in mean sitting diastolic blood pressure (mean reduction 2.17 mmHg, p<0.0001, figure 1), sitting and ambulatory pulse pressure, and 24-h ambulatory systolic blood pressure. LCX696 was well tolerated, and no cases of angio-oedema were reported with the drug – this had been a problem with a previous neprilysin inhibitor compound, omapatrilat.