A growing movement within the medical community is calling on the U.S. Food & Drug Administration (FDA) to require ACE inhibitor blood pressure drugs to carry a ‘black box warning’ – the strictest such warning allowed by law – about the risk of angioedema. This condition is similar to hives, except that it causes swelling beneath the skin rather than at the surface. The controversy surrounding ACE inhibitor side effects is particularly troubling seeing as tens of millions of Americans take the drugs for hypertension, heart disease, strokes, diabetes, and kidney disease.
What’s the Problem with ACE Inhibitors?
“I’ve seen a number of deaths because you just can’t get the tube in,” said James R. Roberts, director of emergency medicine at Mercy Philadelphia Hospital and Mercy Fitzgerald Hospital, which treats more than a case a week of angioedema in ACE inhibitor users. Roberts recently published a letter about with he called an ‘unrecognized epidemic’ in the American Journal of Cardiology, and petitioned the FDA to have ACE inhibitors carry a black box warning.
ACE inhibitors are designed to lower blood pressure by preventing the breakdown of bradykinin, a molecule that causes blood vessels to expand. Research has shown that these widely prescribed drugs reduce hospitalization and death rates, while simultaneously improving patients’ quality of life. Brand name ACE inhibitor blood pressure drugs include:
Generic versions include:
In 2011 alone, approximately 162 million prescriptions were filled for ACE inhibitors, according to IMS health.
Despite the drugs’ considerable ability to lower patients’ blood pressure, ACE inhibitors have been increasingly linked to angioedema, a condition that occurs when swelling develops just below the surface of the skin, most often around the lips or eyes. In an allergic reaction, the body produces histamine, which causes blood vessels to swell. Angioedema is usually caused by an allergic reaction, either to food or prescription medications like ACE inhibitors.
Signs and symptoms of ACE inhibitor-induced angioedema may include:
- sudden appearance of red welts (most often near the eyes and lips, but may also appear on the hands, feet, or the inside of the throat);
- burning, painful, swollen areas;
- discolored patches or rash on the hands, feet, face, or genitals;
- tight or swollen throat;
- breathing trouble;
- muscle pain;
- decreased urine;
- weight gain;
- high white blood cell count
Depending on the severity of the reaction, angioedema can take anywhere from minutes to hours to manifest itself. It may affect an area on one side of the body but not the other, or it may affect both. Severe cases of angioedema may cause the throat or tongue to swell, which may cut off the patient’s airway and result in a life-threatening situation.
Angioedema Cases on the Rise Nationwide
Roberts and his colleagues examined angioedema patients treated at Mercy Catholic and Mercy Fitzgerald, and found that, of 901 cases related to ACE inhibitors:
- 35% required intensive care;
- 4% needed an airway tube;
- one patient died.
“The incidence and potential for [complications] is not appreciated by the public, or by many physicians,” Roberts wrote in the American Journal of Cardiology.
FDA Rejects ACE Inhibitor Black Box Warning
In 2002, Boston University emergency medicine physician James A. Feldman petitioned the FDA to require black box warnings on the labels of ACE inhibitor drugs after a week of three serious cases of angioedema. “One almost died,” he recalled. The administration rejected Robert’s petition, stating that the drugs’ labeling already included a sufficient amount of ‘discussion’ on angioedema.
FDA reserves the black box designation for life-threatening side effects. ACE inhibitor labels already feature a boxed warning regarding an increased risk of birth defects that has been associated with the maternal use of the medications. In rejecting the enhanced warning, the FDA stated that it “likely would not reduce the incidence.”
But Feldman, Roberts, and many others in the medical community say the black box warning would raise much-needed awareness of these issues.
“Not only do patients not know about this, but they don’t know what to do about it,” Feldman said.“They’ll wait until the last minute to get help. Instead, they should be carefully instructed: If you have swelling, stop the drug and call 911, because minutes can matter.”