Use of RAAS Inhibitors Linked to Decreased Risk of Intracranial Aneurysm Rupture

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Use of RAAS Inhibitors Linked to Decreased Risk of Intracranial Aneurysm Rupture

The use of renin-angiotensin-aldosterone system (RAAS) inhibitors reduced the risk of an aneurysm rupture by 18% among patients with hypertension and intracranial aneurysms, according to a study published in Hypertension.

“Approximately half of patients with intracranial aneurysms have high blood pressure, which can cause vascular inflammation and increase the risk of aneurysm rupture,” said Qinghai Huang, MD, Changhai Hospital, Second Military Medical University, Shanghai, China. “Given that one-third of patients with ruptured aneurysms die and another third remain dependent for daily life activities, there is a need to identify modifiable risk factors to prevent aneurysm rupture.”

This study analysed data collected from 2016 to 2021 at 20 medical centres in different regions across China, collected pre- and post-rupture, to evaluate the association among the use of RAAS inhibitors and other blood pressure medications, including beta-blockers and diuretics, on the risk of aneurysm rupture.

More than 3,000 adults with high blood pressure and intracranial aneurysms were included. Participants’ hypertension status was categorised as controlled (normal blood pressure with the use of antihypertensive medications) or uncontrolled (high blood pressure, defined as ≥140/90 with the use of antihypertensive medications), and was determined by blood pressure measurements taken at one point in time, 3 months before they were hospitalised for aneurysm.

The analysis found that 32% of participants who took RAAS inhibitors experienced an intracranial aneurysm rupture, compared with 67% of those who used non-RAAS inhibitors.

“We were surprised to find that even among people with controlled hypertension, those who took RAAS inhibitors still had a significantly lower rupture risk than individuals who used non-RAAS inhibitors,” said Dr. Huang. “Our study highlights that using the proper antihypertensive medications to achieve normalisation of blood pressure may remarkably decrease the risk of a ruptured aneurysm.”

”Based on these data, we estimate that nearly 18% of ruptured aneurysms may be prevented if all patients with high blood pressure and intracranial aneurysms were prescribed with RAAS inhibitors,” he said. “Due to the strong potential benefit and high safety of RAAS inhibitors, these findings may also help clinicians to optimise treatment to help people with high blood pressure prevent aneurysm rupture.”

Using a multivariable model, the researchers calculated that women’s risk of aneurysm rupture was 1.8 times higher than men’s risk, and that the following factors increased the risk of aneurysm rupture: uncontrolled hypertension, exposure to second-hand smoke, and untreated type 2 diabetes.

“These findings confirm previous studies indicating that -- in addition to blood pressure control -- smoking cessation and aggressive treatment of type 2 diabetes may also help reduce the risk of aneurysm rupture,” said Dr. Huang. “However, more research is needed to understand how RAAS inhibitors are involved in the prevention of intracranial aneurysm rupture in adults with high blood pressure.”

The authors noted that limitations include the study’s retrospective nature, the existence of potential confounders, that hypertension was defined as a blood pressure of 140/90, rather than of 130/80, that the exact value of participants’ blood pressure was not taken and that the duration, and dose of RAAS inhibitors was not recorded in the database.

Reference: https://www.ahajournals.org/doi/10.1161/HYPERTENSIONAHA.122.18970

SOURCE: American Heart Association

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— RAAS inhibitors could be therapy of choice for those with hypertension and intracranial aneurysms

by Nicole Lou, Senior Staff Writer, MedPage Today June 6, 2022

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 Hypertension.

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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  Nicole Lou is a reporter for MedPage Today, where she covers cardiology news and other developments in medicine. Follow

Disclosures

The study was funded by government grants from China.

Huang and colleagues had no disclosures.

Primary Source

Hypertension

Source Reference: Zhong P, et al "Effect of renin-angiotensin-aldosterone system inhibitors on the rupture risk among hypertensive patients with intracranial aneurysms" Hypertension 2022; DOI: 10.1161/HYPERTENSIONAHA.122.18970.