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, however 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 ininhibitor labelled LCZ696 was investigated in this study.

1215 patients completed eight-weeks 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 -2.17mm Hg, P<0.0001, figure), sitting and ambulatory pulse pressure, and 24-hour 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.

Conclusions:

LCZ696, a novel anti-hypertensive that inhibits both neprilysin and angiotensin receptors, provided complementary and additive blood pressure reduction when compared to the use of valsartan alone.  Larger scale trials are now needed, but this novel therapeutic approach could potentially confer combined cardiac, vascular and renal protection.

• Ruilope LM, Dukat A, Böhm M, Lacourcière Y, Gong J, Lefkowitz MP. Blood-Pressure reduction with LCZ696, a novel dual-acting inhibitor of the angiotensin II receptor and neprilysin: A randomised, double-blind, placebo-controlled, active comparator study. Lancet 2010, Mar 15.

atriuretic 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, however 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 ininhibitor labelled LCZ696 was investigated in this study.1215 patients completed eight-weeks 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 -2.17mm Hg, P<0.0001, figure), sitting and ambulatory pulse pressure, and 24-hour 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.Conclusions:LCZ696, a novel anti-hypertensive that inhibits both neprilysin and angiotensin receptors, provided complementary and additive blood pressure reduction when compared to the use of valsartan alone.  Larger scale trials are now needed, but this novel therapeutic approach could potentially confer combined cardiac, vascular and renal protection.• Ruilope LM, Dukat A, Böhm M, Lacourcière Y, Gong J, Lefkowitz MP. Blood-Pressure reduction with LCZ696, a novel dual-acting inhibitor of the angiotensin II receptor and neprilysin: A randomised, double-blind, placebo-controlled, active comparator study. Lancet 2010, Mar 15.

Mean Sitting Systolic (Top) and Diastolic Blood pressure changes

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