title: [First Experience of Clinical Application of LCZ696 an AT1-angiotensin Receptors and Neprilysin Inhibitor in Patients With Chronic Heart Failure and Reduced Ejection Fraction].
abstract: Simultaneous inhibition of the renin-angiotensin-aldosterone system and the system of degradation of natriuretic peptides can potentially provide unique therapeutic effects in patients with chronic heart failure (CHF) with reduced ejection fraction (EF). Aim of this study was to assess tolerability of therapy with LCZ696 - first representative of a class of inhibitors of angiotensin receptor and neutral endopeptidase neprilysin - and to study its pharmacodynamic effects.
  
  
  METHODS
  We included into open uncontrolled study 30 patients with stable functional class II-III CHF and EF less or equal 40%. After 24-hour run-in period during which angiotensin converting enzyme inhibitors (ACEI) were withdrawn the patients were given LCZ696 (100 mg/day for 7 days followed by 200 mg/day for 14 days). Other CHF therapy remained unchanged.
  
  
  RESULTS
  Transition from therapy with ACEI to LCZ696 was well tolerated. Three patients were excluded because of hyperkalemia more or equal 5mmol/l. After 21 days of treatment elevation of plasma biomarkers of inhibition of neprilysin and angiotensin receptors occurred: cyclic guanosine monophosphate, renin concentration and activity rose 1.38, 3.50, and 2.27 times from baseline level (<0.05 for all). After 7 and 21 days of LCZ696 administration we noted significant lowering of NT-proBNP; significant lowering of aldosterone and endothelin-1 in blood plasma was observed on day 21.
  
  
  CONCLUSIONS
  Administration of LCZ696 to patients with CHF with reduced ejection fraction (EF) was well tolerated and associated with potentially favorable for this category of patients dynamics of biomarkers.
authors.affiliation: Peoples Friendship University of Russia (PFUR), Moscow, Russia.
authors.forename: Zh D
authors.initials: ZD
authors.lastname: Kobalava
authors.affiliation: Peoples Friendship University of Russia (PFUR), Moscow, Russia.
authors.forename: E P
authors.initials: EP
authors.lastname: Pavlikova
authors.affiliation: Peoples Friendship University of Russia (PFUR), Moscow, Russia.
authors.forename: O A
authors.initials: OA
authors.lastname: Averkov
authors.affiliation: Peoples Friendship University of Russia (PFUR), Moscow, Russia.
authors.forename: I
authors.initials: I
authors.lastname: Merai
authors.affiliation: Peoples Friendship University of Russia (PFUR), Moscow, Russia.
authors.forename: L A
authors.initials: LA
authors.lastname: Babaeva
authors.affiliation: Peoples Friendship University of Russia (PFUR), Moscow, Russia.
authors.forename: I A
authors.initials: IA
authors.lastname: Amirbegishvili
authors.affiliation: Peoples Friendship University of Russia (PFUR), Moscow, Russia.
authors.forename: Yu V
authors.initials: YV
authors.lastname: Kotovskaya
authors.affiliation: Peoples Friendship University of Russia (PFUR), Moscow, Russia.
authors.forename: V S
authors.initials: VS
authors.lastname: Moiseev