9C.04: TREATMENT WITH LCZ696 COMPARED TO AT1-RECEPTOR BLOCKADE IS ASSOCIATED WITH NON-SUSTAINED INCREASES OF NATRIURESIS AND DIURESIS IN ASIAN PATIENTS WITH SALT-SENSITIVE HYPERTENSION. (June 2015)

• Record Type: Journal Article
• Authors: Wang, T.D.; Tan, R.S.; Lee, H.; Ihm, S.H.; Rhee, M.Y.; Tomlinson, B.; Pal, P.; Yang, F.; Hirschhorn, B.; Hinder, M.; Langenickel, T.H.
• Is Part Of: Journal of hypertension. Volume 33(2015)Supplement 1
• Publication Date: 2015-06
• Subjects: Hypertension -- Periodicals; Hypertension -- Periodicals; 616.132005
• DOI: 10.1097/01.hjh.0000467685.39554.d4
• Languages: English
• ISSNs: 1473-5598

Abstract

Abstract : Objective: Patients with salt-sensitive hypertension (SSH) retain sodium in response to salt load and display a relative deficiency of atrial natriuretic peptide (ANP). LCZ696 is an angiotensin receptor neprilysin inhibitor (ARNI) expected to increase ANP levels while simultaneously blocking the AT1-receptor. This study investigated the effects of LCZ696 compared to valsartan on natriuresis and diuresis in Asian patients with SSH. Design and method: Randomized, double-blind, cross-over study in 72 patients with SSH (10% or higher increase in MAP when switching from 50 mmol/day to 320 mmol/day for 7 days each). Patients received LCZ696 400 mg once daily and valsartan 320 mg once daily for 4 weeks each. Natriuresis and diuresis were assessed for 6 h and 24 h after dosing on Days 1 and 28. Results: On Day 1, LCZ696 but not valsartan resulted in significant increases from baseline in 6 h natriuresis (p < 0.001) and in 24 h natriuresis (p < 0.001). LCZ696 compared to valsartan demonstrated a significantly higher Day 1 natriuresis for the 6 h (adjusted treatment difference: 24.5 mmol; p < 0.001) and the 24 h intervals (adjusted treatment difference: 50.3 mmol; p < 0.001). On Day 28, 6 h and 24 h natriuresis were comparable to baseline and not different between treatment groups. On Day 1, LCZ696 but not valsartan resulted in significant increases from baseline in 6 h diuresis (p < 0.001) and in 24 h diuresis (p < 0.001). LCZ696 compared to valsartan demonstrated a significantly higher Day 1 diuresis for the 6 h (adjusted treatment difference: 291.2 mL; p < 0.001) and the 24 h intervals (adjusted treatment difference: 356.4 mL; p = 0.003). On Day 28, 6 h and 24 h diuresis were comparable to baseline and not different between treatment groups. Plasma sodium and potassium levels were not different between treatment groups. Conclusions: Treatment with LCZ696 400 mg compared to valsartan 320 mg once daily for 4 weeks was associated with non-sustained increases in natriuresis and diuresis. This differentiates LCZ696 from diuretics and ARBs and may suggest an added long-term benefit with respect to improved sodium balance in patients with SSH.