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The chances of intracranial aneurysms rupturing were lower in people taking renin-angiotensin-aldosterone system (RAAS) inhibitors for hypertension, a Chinese study showed.

In a multicenter database counting over 3,000 people with these aneurysms registered in 2016-2021, rupture rates reached 23.4% in RAAS inhibitor users and 76.6% in non-users, according to Qinghai Huang, MD, PhD, of Changhai Hospital, Second Military Medical University, in Shanghai, and colleagues.

The use of RAAS inhibitors was associated with a significantly reduced risk of intracranial aneurysm rupture (OR 0.490, 95% CI 0.402-0.597), and this applied to angiotensin-converting enzyme (ACE) inhibitors (OR 0.559, 95% CI 0.442-0.709) and angiotensin receptor blockers (ARBs) alike (OR 0.414, 95% CI 0.315-0.542), they noted in .

The decreased rupture risk associated with RAAS inhibitors persisted across subgroups by age, sex, BMI, control of hypertension, monotherapy and combination therapy, and location and size of intracranial aneurysms.

Huang and colleagues highlighted the relative safety and affordability of RAAS inhibitors and suggested that a randomized trial be conducted to confirm whether these medications protect against aneurysm rupture.

Hypertension is a known risk factor for intracranial aneurysm rupture, the cause of most subarachnoid hemorrhage strokes.

There is some evidence that RAAS activation may be involved in the pathogenesis of intracranial aneurysms, according to the study authors.

"In hypertension, the RAAS has wide-ranging effects on blood pressure regulation through sodium retention, pressure natriuresis, salt sensitivity, vasoconstriction, endothelial dysfunction, and vascular injury. Given these facts, in addition to the directly increasing hemodynamic stresses, activation of the RAAS by systemic hypertension can cause vascular inflammation, injury, and remodeling and thereby contribute to the process of intracranial aneurysm rupture," they explained.

Huang's group nevertheless acknowledged that it's unclear how inhibiting RAAS would prevent aneurysm rupture. A prospective study could shed light on the mechanism, they said.

For this retrospective study, the authors reviewed the records of patients across 20 Chinese academic medical centers.

Their database included 3,044 adults (mean age 61, 36.6% men) who were on blood pressure medications and had an intracranial aneurysm, split between those whose aneurysms had ruptured (n=1,238) or had not ruptured (n=1,806) by the time of analysis. Aneurysms could be treated by clipping, coiling, and/or conservative treatment.

In a secondary analysis matching 541 RAAS inhibitor users with the same number of non-users, Huang's group found that 17.7% of ruptured aneurysms would be prevented if all patients were prescribed RAAS inhibitors.

Besides RAAS inhibitor non-use, other independent predictors of rupture included female sex, passive smoking, uncontrolled or unmonitored hypertension, hyperlipidemia, and aneurysmal location outside the internal carotid artery.

"Our study importantly extends previous studies of blood pressure control, treating hyperlipidemia and diabetes aggressively, and avoiding passive smoking as second [prevention] for these patients," the authors wrote.

Nonetheless, the retrospective study left room for residual confounding and the database lacked key clinical variables, such as blood pressure measurements and duration and dose of RAAS inhibitor therapy.

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