Dose-dependent reduction of blood pressure by angiotensin receptor-neprilysin inhibitor: A network meta-analysis

Context: Angiotensin receptor-neprilysin inhibitor (ARNi) has been established as the standard medication for heart failure. However, the blood pressure (BP)-lowering effect circumvented its administration and titration in patients with borderline hypotension. Aim: This study aimed to determine the correlation between ARNi dosage and hemodynamic impacts. Subjects and Methods: A network meta-analysis was conducted to interrogate the BP impact of ARNi (sacubitril/valsartan 100 mg/d, 200 mg/d, 400 mg/d) and angiotensin receptor blocker (ARB) counterparts. Individuals with mild-to-moderate systolic hypertension were enrolled in respective studies. The outcomes were set as the change from baseline systolic and diastolic BP. Statistical Analysis Used: Network meta-analysis, node-splitting, and inconsistency model methods in Bayesian approach were employed. Results: A total of 14 manuscripts with 7705 subjects were included for pooled analysis. Compared with ARB, sacubitril/valsartan 400 mg/d and 200 mg/d, but not 100 mg/d, were associated with significantly greater reduction effect of systolic and diastolic BP, either by office documentation or 24-h ambulatory monitoring. The BP-lowering effect of sacubitril/valsartan 400 mg/d and 200 mg/d was nevertheless equivalent. Conclusions: ARNi exerts a dose-dependent effect on BP reduction. Such hemodynamic impact exceeds ARB at higher doses.