Airway Angioedema Triggered by ACE Inhibitor Not Eased by Berinert

About a third of emergency room angioedema cases caused by ACE inhibitor

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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A single dose of Berinert, a concentrate of C1 esterase inhibitor, when given with standard treatment, may not do more to ease angioedema airway symptoms triggered by a type of medication called an angiotensin-converting enzyme (ACE) inhibitor, a study found.

The study, “Efficacy of human C1 esterase inhibitor concentrate for treatment of ACE-inhibitor induced angioedema,” was published in the American Journal of Emergency Medicine.

Angioedema may arise as a side effect of some medications. When this happens, it’s called non-allergic angioedema.

An ACE inhibitor is a medication normally used to treat high blood pressure. It works by increasing the levels of bradykinin, a molecule that makes blood vessels relax and widen, helping to lower blood pressure. But bradykinin also makes blood vessels more permeable, allowing fluid to leak out and pool into nearby tissues, causing them to swell.

When swelling occurs in the airways, it can prevent air from moving in and out of the lungs. This may require emergency care. Around a third of angioedema cases in emergency rooms are triggered by an ACE inhibitor.

The standard emergency treatment for angioedema attacks is a combination of glucocorticoids and antihistamines, but these generally don’t work well for non-allergic angioedema since it isn’t driven by an allergic reaction, unlike other types of angioedema.

Berinert is a C1 inhibitor concentrate approved to treat attacks of hereditary angioedema, a type of angioedema that’s caused by having too little C1 inhibitor. The C1 inhibitor protein helps keep the immune system in check, in part by controlling the amount of bradykinin that’s produced.

The idea of using Berinert to treat angioedema attacks triggered by an ACE inhibitor has come up before. In a small study from Canada, the off-label use of C1 inhibitor eased swelling and shortened how long some people needed emergency care.

A team of researchers in Germany tested how well Berinert works against a placebo when given as a single intravenous (into-the-vein) injection on top of standard treatment to ease airway symptoms.

The study (Eudra-CT 2012-001670-28) included 30 adults, ages 50 and older, with angioedema triggered by an ACE inhibitor who had airway obstruction; 16 received a single dose of intravenous Berinert and 14 were given a placebo. Standard treatment was a combination of the glucocorticoid prednisolone and the antihistamine clemastine.

The median time to full resolution of swelling in the lips, tongue, and throat was nine hours longer in the Berinert group than the placebo group (24 vs. 15 hours). This means Berinert was worse than a placebo at easing symptoms.

The median time to onset of relief, which was defined as a one-point reduction in a composite scale that measured the severity of four symptoms on a range from 1–4 points, was two hours in both groups. 

There were no side effects related to using Berinert.

While it wasn’t seen to ease airway symptoms, researchers said it’s perhaps “too early to fully reject” its use with angioedema triggered by an ACE inhibitor.

If available, Firazyr (icatibant) or Berinert “should be considered whenever there is no restitution or even a worsening of airway compromise under glucocorticoids and antihistamines,” the researchers wrote. Firazyr is another approved medication for hereditary angioedema.