Renin Profiling Predicts Neurohormonal Response to Sacubitril/Valsartan

AIMS: Clinical trials and observational cohorts show that beneficial effects of sacubitril/valsartan are less strong in an appreciable proportion of patients with heart failure with reduced ejection fraction (HFrEF). Lower blood pressure and impaired renal function predict suboptimal sacubitril/valsartan titration and a less favourable response. Circulating renin encompasses neurohormonal activation, intravascular volume, and renal function. We hypothesized that renin may predict response to sacubitril/valsartan, assessed by changes in N-terminal fraction of pro-brain natriuretic peptide (NT-proBNP). METHODS AND RESULTS: We performed a prospective, open-label, real-life cohort study. The study population consisted of 80 consecutive HFrEF patients (age 66 ± 10 years, 83% men) planned to initiate sacubitril/valsartan. Clinical and biohumoral assessment, including a full neurohormonal panel, was performed at baseline and at 1, 3, and 6 month follow-up. Response to sacubitril/valsartan was defined as ≥30% reduction in NT-proBNP levels from baseline to 6 months. Patients in the lower renin tertile had higher blood pressure and plasma sodium concentration (all P < 0.05). At follow-up, 38 patients (48%) were classified as responders. Circulating renin was lower in the responder group compared with non-responders (19.8 mU/L, IQR 3.7-78.0 mU/L vs. 55.0 mU/L, IQR 16.4-483.1 mU/L; P = 0.004). After adjustment for age, renal function, and blood pressure, renin was independently associated to response to sacubitril/valsartan (P = 0.018). CONCLUSIONS: In our preliminary study, we show that circulating renin predicts reduction in NT-proBNP levels after sacubitril/valsartan initiation in HFrEF patients. Renin assessment might be useful to discriminate potential responders from the subgroup with a weaker expected benefit, thus needing a closer, tailored management strategy.