ACE inhibitors may cause localized swelling: study

NEW YORK (Reuters Health) - The risk of angioedema -- localized swelling in the deep layers of the skin that usually affects the face, throat, lips or tongue -- is more than 3 times higher with a class of blood pressure-lowering drugs called angiotensin converting enzyme (ACE) inhibitors than with other "antihypertensive" drugs, research suggests.

While angioedema associated with ACE inhibitors is relatively rare, its incidence and determinants have not been well defined, Dr. Donald R. Miller from the Veterans Affairs (VA) Medical Center in Bedford, MA and colleagues explain.

They identified all patients in the VA health care system who received first prescriptions for ACE inhibitors between April 1999 and December 2000. The most commonly prescribed agents were lisinopril, fosinopril, and captopril.

The angioedema incidence rate in these patients was 1.97 cases per 1000 persons per year, Miller and colleagues report, compared with a rate of 0.47 in this group before initiating ACE inhibitors and 0.51 in a comparison group of patients taking other antihypertensive drugs.

The relative risk of angioedema for new ACE inhibitor users was 3.56 times that of new users of other antihypertensive drugs, the researchers note, and the risk was elevated for all ACE inhibitors individually.

"We project that about 1 of every 2600 new ACE users experiences angioedema within 30 days and about 1 of every 1000 experiences it within a year after first use," the investigators say. "It also is evident that risk remains elevated with continued ACE use, even more than 1 year after initiation."

Other factors independently associated with an increased risk of angioedema included black race, female gender, and chronic heart failure or coronary artery disease. Diabetes significantly decreased the risk of angioedema.

"The challenge," Miller and colleagues say, "will be to better identify those subgroups at the highest risk for angioedema in whom the risks of ACE therapy may outweigh the benefits."

In a commentary published with the study, two doctors from New York, write, "Clearly, when considering the use of ACE inhibitor therapy in black patients, the increased risk of angioedema should be taken into account and discussed with the patients."

"Even so, ACE inhibitors have been valuable in preventing fatal and nonfatal cardiovascular and renal events in patients at risk, and it is likely that they will continue to be prescribed in the foreseeable future," note Dr. Michael A. Weber from Downstate College of Medicine and Dr. Franz H. Messerli from St. Luke's-Roosevelt Medical Center.

SOURCE: Hypertension, June 2008.