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Sacubitril/Valsartan for Refractory Hypertension in Acute Intracerebral Hemorrhage: A Single-Center Retrospective
Koki Ito1, Shinsuke Sato1, Akitsugu Kawashima1
1Department of Neurosurgery, St. Luke's International Hospital, Tokyo, JPN.
Insights
Early use of sacubitril/valsartan (ARNI) in acute intracerebral hemorrhage (ICH) patients with refractory hypertension led to faster blood pressure stabilization and simpler medication regimens. This supports ARNI as a practical option for managing blood pressure in ICH.
Area of Science:
- Neurology
- Cardiology
- Pharmacology
Background:
- Intracerebral hemorrhage (ICH) presents high early mortality risks.
- Current guidelines mandate rapid systolic blood pressure reduction to <140 mmHg.
- Managing refractory hypertension in ICH often requires complex, prolonged intravenous and oral antihypertensive therapies.
Purpose of the Study:
- To evaluate the real-world effectiveness of sacubitril/valsartan (ARNI) as a second-line oral antihypertensive in patients with acute ICH and refractory hypertension.
- To compare antihypertensive regimen stabilization time and complexity between ARNI users and historical controls.
Main Methods:
- A single-center retrospective cohort study compared 30 ICH patients receiving ARNI with 30 historical controls.
- The primary endpoint was time to antihypertensive regimen stabilization.
- Secondary outcomes included the number of oral antihypertensives at stabilization and discharge modified Rankin Scale (mRS) scores.
Main Results:
- ARNI use was independently associated with a significantly shorter time to antihypertensive regimen stabilization (p=0.045).
- Patients on ARNI required fewer scheduled oral antihypertensives at stabilization (p=0.006).
- Discharge mRS scores were similar between the ARNI and non-ARNI groups.
Conclusions:
- Early integration of ARNI as a second-line agent in acute ICH management simplifies antihypertensive regimens.
- ARNI demonstrates utility in goal-oriented blood pressure management for ICH patients.
- Findings provide hypothesis-generating data for future prospective research on ARNI in ICH.
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.
