Angiotensin Inhibition Reduces the Risk of Subarachnoid Hemorrhage in Patients With Hypertension

Local angiotensin activity is thought to play a critical role in arterial wall homeostasis and remodeling, and impaired arterial wall integrity contributes to the pathogenesis of subarachnoid hemorrhage (SAH). Here we aimed to assess the association between pharmacologic inhibition of angiotensin-converting enzyme and subsequent nontraumatic SAH.

In a retrospective cohort study based on Optum's Clinformatics Datamart deidentified database records (2000-2021), we included all subjects with a history of hypertension. We collected medication history, and the exposure of interest was the use of an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker (ACEI/ARB). The primary outcome was the subsequent development of nontraumatic SAH. Cox proportional hazard regression models were used to compare the time to SAH by type of antihypertensive treatment.

A total of 7.5 million patients with hypertension were assessed. Patients on ACEI/ARBs with or without other antihypertensives (n = 4.8 million, follow-up: 6.3 years) had lower rates of SAH compared with those on alternative antihypertensive regimens (n = 1.3 million, follow-up: 5.7 years) (hazard ratio [HR]:0.94 [0.91-0.97]; P<0.0001), as well as compared with those on no antihypertensive medications (n = 1.4 million, follow-up: 5.3 years) (HR:0.94 [0.91-0.97]; P = 0.0002). However, antihypertensive medications other than ACEI/ARBs were not associated with SAH risk compared with treatment by no antihypertensives (HR:1.00 [0.97-1.04]; P = 0.83). Among 8034 patients with known unruptured intracerebral aneurysms, no difference in SAH with ACEI/ARBs was observed compared to alternative antihypertensive regimens (HR:1.04 [0.95-1.13]) or no antihypertensive therapy (HR:1.06 [0.97-1.16]). Uninterrupted ACEI/ARBs use for ≥3 years reduced the risk of SAH by 23%, compared with treatment by only other hypertensives (HR:0.71 [0.68-0.74]; P<0.001).

Treatment of hypertension with ACEI/ARBs was associated with a lower risk of SAH than other types of antihypertensive agents, particularly with longer courses of therapy.