Abstract Body: Background: Local angiotensin activity is thought to play a critical role in arterial wall homeostasis and remodeling, which contributes to the pathogenesis of subarachnoid hemorrhage (SAH). Here we aimed to assess the association between pharmacologic inhibition of angiotensin-converting enzyme and subsequent non-traumatic SAH

Methods: In a retrospective cohort study based on Optum’s Clinformatics® Datamart de-identified Database records (2000-2021), patients with hypertension were included. We collected medication history and assessed the risk of non-traumatic subarachnoid hemorrhage (SAH) associated with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACEI/ARB). Cox proportional hazard regression models were used to compare the time to SAH by type of antihypertensive treatment. Analyses were adjusted for baseline demographic and clinical characteristics

Results: 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, average age 61.9, 50.4% female) had lower rates of SAH compared to those on alternative antihypertensive regimens (n=1.3 million, follow-up:5.7 years,average age 61.9, 60.3%female) [HR:0.94(0.91-0.97), p<0.0001] and compared to those on no antihypertensive medications (n=1.4 million,follow-up: 5.3 years, average age 61.0, 50.8% female) [HR:0.94 (0.91-0.97), p=0.0002]. However, patients on non-ACEI/ARBs anti-hypertensive medications had a similar risk of SAH risk compared to those not on any antihypertensives [HR:1.00(0.97-1.04), p=0.83]. Uninterrupted ACEI/ARBs use for ≥3 years reduced the risk of SAH by 23%, compared to treatment by only other hypertensives (HR:0.77[0.73-0.80], p<0.001). Among the subgroup of patients with known unruptured intracerebral aneurysms (n=8034), no difference in SAH with ACEI/ARBs was observed compared to alternative antihypertensive regimens [HR:1.04(0.95-1.13), p=0.39] or no antihypertensive therapy [HR:1.06(0.97-1.16), p=0.20]. No difference in rate of SAH was observed in patients with intracerebral aneurysms who were treated by only ACEI antihypertensives [HR:1.03(0.93-1.13),p=0.59] or by only ARB antihypertensives [HR: 1.01 (0.90-1.13),p=0.87] compared to patients on only antihypertensives other than ACEI or ARBs

Conclusion: Treatment of hypertension with ACEI/ARBs was associated with a lower risk of SAH compared to other antihypertensive agents, particularly with longer courses of therapy