Abstract
INTRODUCTION: Intracerebral hemorrhage (ICH) is associated with high early mortality. Guidelines recommend a rapid and sustained reduction of systolic blood pressure to <140 mmHg. Achieving and maintaining this target in refractory hypertension often requires prolonged intravenous therapy and complex escalation of oral antihypertensive regimens. Sacubitril/valsartan, an angiotensin receptor-neprilysin inhibitor (ARNI), combines renin-angiotensin blockade with natriuretic peptide augmentation and has proven antihypertensive efficacy; however, data about its real-world use during the acute phase of ICH remain limited. METHODS: We performed a single-center retrospective cohort study of consecutive patients with acute ICH and untreated refractory hypertension. Following the institutional introduction of ARNI in 2022, patients receiving ARNI as a scheduled second-line oral antihypertensive were compared with historical controls. The primary endpoint was time to antihypertensive regimen stabilization, defined as the time point at which escalation of scheduled oral antihypertensives was no longer required and intravenous or rescue short-acting antihypertensives were discontinued. Secondary outcomes included the number of scheduled oral antihypertensives at stabilization and the discharge modified Rankin Scale (mRS) scores. RESULTS: Thirty patients with ARNI (ARNI group: 2022-2024) and 30 consecutive historical controls (non-ARNI group: pre-2021) were included. Baseline characteristics were similar between groups. The mean time to antihypertensive regimen stabilization tended to be shorter in the ARNI group, i.e., 119.6 hours in the ARNI group and 143.3 hours in the non-ARNI group (unadjusted p = 0.275). In multivariable linear regression, ARNI use was independently associated with shorter stabilization time (partial regression coefficients (B) = -40.427 hours; 95% confidence interval (CI): -79.833 to -1.021; p = 0.045). At stabilization, the ARNI group required fewer scheduled oral antihypertensives compared to controls (median: 2.0 (interquartile range: 2.0-2.0) vs. 2.0 (2.0-3.0); p = 0.030; adjusted B = -0.483; 95% CI: -0.825 to -0.140; p = 0.006). The discharge mRS scores did not differ between the groups. CONCLUSIONS: In our routine clinical practice, early incorporation of ARNI as a second-line oral antihypertensive in acute ICH was associated with earlier completion of antihypertensive regimen adjustment processes and reduced treatment complexity. These results support the usefulness of ARNI as a practical second-line antihypertensive for goal-oriented blood pressure management and provide hypothesis-generating data for future prospective studies.