RAAS inhibitors shown to reduce risk of intracranial aneurysm rupture in hypertensive patients

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A multicentre study of more than 3,000 people with high blood pressure and brain aneurysms found that the use of renin-angiotensin-aldosterone system (RAAS) inhibitors—a class of blood pressure-lowering medications—reduced the risk of an aneurysm rupture by 18%. These findings have been published in the journal Hypertension.

“Approximately half of [all] patients with intracranial aneurysms have high blood pressure, which can cause vascular inflammation and increase the risk of aneurysm rupture,” said the study’s senior author Qinghai Huang (Changhai Hospital Affiliated To 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.”

The body’s RAAS includes hormones that affect blood pressure regulation, and dysregulation of the RAAS can lead to the development of high blood pressure. Two components of RAAS have been shown to be involved in the development of intracranial aneurysms, and previous research has found that dysregulation of RAAS may also contribute to aneurysm rupture. Medications that block the effects of the RAAS, known as RAAS inhibitors, are often used to treat high blood pressure.

Huang and colleagues’ study analysed data collected from 2016 to 2021 at 20 medical centres in different regions across China, both pre- and post-rupture, to evaluate the impact of 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. The study sample was one-third men and two-thirds women, with an average age of 61 years. Participants’ hypertension status was categorised as controlled (normal blood pressure with the use of antihypertensive medications) or uncontrolled (high blood pressure, defined as 140/90mmHg or above, with the use of antihypertensive medications), and was determined by blood pressure measurements taken at one point in time—three months before they were hospitalised for aneurysm.

The analysis found that 32% of participants who took RAAS inhibitors experienced an intracranial aneurysm rupture, compared to 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,” Huang continued. “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. Due to the strong potential benefit and high safety of RAAS inhibitors, these findings may also help clinicians to optimize 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,” Huang added. “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 of their study included its retrospective nature, the existence of potential confounders, the fact that hypertension was defined as a blood pressure of 140/90mmHg (rather than of 130/80mmHg), the exact value of participants’ blood pressure not being taken, and the duration and dose of RAAS inhibitors not being recorded in the database.

Nonetheless, Huang and colleagues conclude their Hypertension paper by stating that “the use of RAAS inhibitors was significantly associated with a decreased rupture risk independent of blood pressure control among hypertensive patients with intracranial aneurysms”.


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