Renin-related changes after sequential switching from aliskiren to valsartan and sacubitril/valsartan in patients with a high-renin phenotype: a prospective pilot study.

BACKGROUND: A high-renin phenotype suggests renin-dependent activation of the renin-angiotensin-aldosterone system (RAAS), for which direct renin inhibition may be a mechanistically relevant approach. After discontinuation of aliskiren in Japan, aliskiren-treated patients required transition to alternative RAAS inhibitors. We evaluated renin-related changes during sequential switching from aliskiren to valsartan and sacubitril/valsartan. METHODS: This single-center, prospective, open-label pilot study included aliskiren-treated patients with a high-renin phenotype. Patients were switched to valsartan for 8 weeks and then to sacubitril/valsartan for 16 weeks. Plasma renin activity (PRA), active renin concentration (ARC), and plasma aldosterone concentration (PAC) were assessed with blood pressure, estimated glomerular filtration rate (eGFR), and echocardiographic parameters. Hormonal variables are shown as medians [25th-75th percentiles]. TRIAL REGISTRATION: UMIN000057149. RESULTS: Eight patients (median age, 47.5 years; 50% male) were analyzed. After switching to valsartan, PRA increased from 0.6 [0.1-2.5] to 5.5 [3.2-15.8] ng/mL/h, and ARC increased from 2.5 [0.8-7.7] to 20.2 [16.9-45.6] pg/mL, whereas no further marked increase was observed during sacubitril/valsartan treatment. PAC did not change significantly. Systolic blood pressure increased during the valsartan phase and decreased after sacubitril/valsartan initiation. eGFR showed no progressive deterioration. Left atrial volume index increased at 24 weeks, whereas other filling pressure indices did not change. CONCLUSION: In this small prospective pilot study, sequential transition from aliskiren to valsartan and sacubitril/valsartan was associated with renin-related changes without progressive renal deterioration. These preliminary findings may help characterize RAAS-related responses during treatment transition in selected patients with a high-renin phenotype.