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PP.07.24: TREATMENT WITH LCZ696 COMPARED TO AT1-RECEPTOR BLOCKADE PROVIDES SUPERIOR BP CONTROL AND RESULTS IN LARGER NT-PROBNP REDUCTIONS IN ASIAN PATIENTS WITH SALT-SENSITIVE HYPERTENSION

Objective: Salt-sensitivity is associated with exaggerated blood pressure (BP) increase in response to salt load and considered an independent predictor of cardiovascular events in normo- and hypertensive individuals. LCZ696 is an angiotensin receptor neprilysin inhibitor (ARNI) expected to increase ANP levels while simultaneously blocking the AT1-receptor. This study compared the effects of LCZ696 and valsartan on BP and NT-proBNP in Asian patients with salt-sensitive hypertension (SSH). Design and method: Randomized, double-blind, double-dummy 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. Office BP, ambulatory blood pressure measurements (ABPM) and NT-proBNP were assessed at baseline and on Day 28. Results: LCZ696 and valsartan significantly lowered office SBP and office DBP from baseline with larger reductions with LCZ696 compared to valsartan (SBP: -13.3 mmHg vs. -5.9 mmHg; adjusted mean difference between groups: -7.6 mmHg, p = 0.002; DBP: -6.2 mmHg vs. -4.3 mmHg; adjusted mean difference between groups: -2.0 mmHg, p = NS). LCZ696 and valsartan also significantly lowered ambulatory SBP, DBP, MAP, and pulse pressure from baseline with larger reductions with LCZ696 compared to valsartan for daytime, nighttime, and 24 h intervals. The largest treatment difference between groups was observed at nighttime (adjusted mean difference; SBP: -5.1 mmHg, p < 0.001; DBP: -2.6 mmHg, p = 0.004; MAP: -4.0 mmHg, p < 0.001). Baseline plasma NT-proBNP levels were comparable between groups. On Day 28, NT-proBNP levels were significantly reduced by 41% with LCZ696 and by 28% with valsartan (p < 0.001 for both). NT-proBNP at week 4 was significantly lower (20%) with LCZ696 compared to valsartan (p = 0.001). Conclusions: Treatment with LCZ696 400 mg compared to valsartan 320 mg once daily for 4 weeks provided superior office and ambulatory blood pressure reduction and larger hemodynamic unloading of the heart. These results may suggest an added long-term benefit for LCZ696 related to reduction of end-organ damage and cardiovascular events in patients with SSH.