Kate Johnson

March 19, 2012

March 19, 2012 (Orlando, Florida) — Hospitalization rates for nonhereditary angioedema have risen significantly over the past decade, particularly in blacks, largely because of adverse reactions to antihypertensive and other cardiovascular drugs, according to a study presented at the American Academy of Allergy, Asthma and Immunology 2012 Annual Meeting.

The findings, which show an almost 8% requirement for ventilatory assistance with the disease, might provide impetus for further investigation into certain medications currently only approved for hereditary angioedema, said Robert Lin, MD, a specialist in allergy and immunology at New York Downtown Hospital and professor of medicine at New York Medical College in New York City.

"It would be good if we had better treatments for ACE [angiotensin-converting-enzyme]-inhibitor–associated angioedema so that when it occurs, we can prevent some of these hospitalizations," he told Medscape Medical News. "Some of these [hereditary angioedema] drugs have been shown to be helpful; maybe if we could use them in the emergency department, not all of these patients would have to be admitted."

His team queried the Nationwide Inpatient Sample database from 2000 to 2009 for angioedema hospitalizations (International Classification of Diseases [ICD] code 995.1) and other allergy-related hospitalizations coded as allergy unspecified (code 995.3), other anaphylaxis (code 995.0), or allergic urticaria (code 708.0).

From 2000 to 2009, the percentage of nonhereditary angioedema hospitalizations rose significantly in the United States, from 3.4 to 5.4 per 100,000 (P < .0001), whereas other allergy-related hospitalizations remained stable at 1.5 per 100,000.

Blacks made up 37% of all angioedema hospitalizations, and had the highest increase in hospitalizations — from 8.9 per 100,000 in 2000 to 18.0 per 100,000 in 2009 (odds ratio [OR], 3.57, compared with nonblack patients; P < .0001), Dr. Lin reported.

For angioedema hospitalizations, compared with other allergy-related hospitalizations, the odds were higher for 4 conditions treated with ACE inhibitors: hypertension (OR, 1.83); diabetes mellitus (OR, 1.20); chronic kidney disease (OR, 1.48); and congestive heart failure (OR, 1.19).

Adverse drug effects related to antihypertensive and other cardiovascular medications were coded in 29% of all patients, in 38% of black patients, and in 25% of patients of other races.

Although only 0.4% of hospitalized angioedema patients died, the condition has significant morbidity. Mechanical ventilation, endotracheal intubation, and temporary tracheostomy were coded in 5.6%, 6.3%, and 1.4%, respectively, Dr. Lin reported.

He pointed out that with the increasing use of ACE inhibitors, it is important to know what to expect if there is an angioedema reaction.

"Anaphylaxis tends to be much quicker in terms of its development, whereas angioedema can get worse over a few hours," he said. "Patients can get swelling of the tongue and larynx, which could go on and close off their airway; that's why they have to be watched carefully. You can't carry an epipen like you would with food allergies; epinephrine doesn't work. Basically, you have to come to the hospital to make sure you don't die."

He said although most people will have a reaction to ACE inhibitors within the first month of treatment, sometimes there can be a delayed reaction.

"There were many people who developed a reaction after being on them for years. In the old days, some doctors didn't really recognize this. They would put the person back on an ACE inhibitor and they would have to be reintubated for angioedema. I've seen that before."

In addition to race, age, and ACE-inhibitor-treated comorbidities, logistic regression analysis identified predictors of ventilator-assisted hospitalizations to be alcohol disorders (OR, 1.2) and influenza/pneumonia (OR, 9.2).

Alcohol has also been reported to be a trigger in the arthritis, hives, angioedema (AHA) syndrome. A previous study identified alcohol use as a predictor of angioedema hospitalization (Ann Otol Rhinol Laryngol. 2010;119:836-841), he noted.

"If you drink alcohol and you take ACE inhibitors...that's definitely a risk factor that people should be aware of," he said, adding that the association with alcohol could include "anything from acute intoxication to withdrawal or some other complication of long-term alcoholism."

Dr. Lin noted that several case reports have noted the utility of "fairly expensive" medications, such as icatibant (a bradykinin receptor antagonist) and ecallantide (a kallikrein inhibitor), which are only approved for hereditary angioedema. There is an ongoing phase 2 study testing the efficacy of ecallantide in the treatment in ACE-inhibitor-associated angioedema.

Commenting on the findings, David Elkayam, MD, from the Bellingham Asthma, Allergy, and Immunology Clinic in Washington, said: "I do think that the knowledge gained from this orphan disease — hereditary angioedema — might someday translate into more effective treatment for other forms of nonhereditary but bradykinin-driven angioedema."

However, he called the current cost of hereditary angioedema treatments (up to $10,000 a dose) "prohibitive."

"I wish there was a test available to predictably guide treatment regarding who the positive responders will be," he said.

The speakers have disclosed no relevant financial relationships.

American Academy of Allergy, Asthma and Immunology (AAAAI) 2012 Annual Meeting: Abstract 834. Presented March 6, 2012.

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