Doctors in Britain have been warned about a rare side effect of ACE inhibitors that may affect patients and might even appear after weeks or years of taking the medication.
In a drug safety update, the Medicines and Healthcare products Regulatory Agency (MHRA) said doctors, particularly those working in emergency departments, needed to watch out for the possibility of delayed-onset angioedema in people taking the medication.
“There is the potential for delayed onset of angioedema, and health professionals should be aware of the distinction between bradykinin- and histamine-mediated cases, as treatment strategies differ significantly and bradykinin-mediated angioedema does not respond to standard treatment,” the MHRA said.
The alert follows a review of data by Canadian experts which found that half of angioedema cases occurred 30 days or more after starting treatment – higher than the 20%-30% indicated by the manufacturers, the MHRA said, while noting that the delayed-onset pattern was “more associated with the non-allergic bradykinin-mediated angioedema”.
This is unlikely to respond to standard anaphylaxis treatments including adrenaline (epinephrine), which should prompt consideration of a non-allergic cause, the MHRA guidance stated.
Doctors have been advised to let patients know that although uncommon or rare, angioedema (swelling of the face, lips, tongue, or throat) can occur at any time while taking an ACE inhibitor, even if they have been taking it for a long time without problems.
Study details
Bradykinin-induced angioedema in the emergency department
Jacques Hébert, Jean-Nicolas Boursiquot, Hugo Chapdelaine et al.
Abstract
Background
Acute airway angioedema commonly occurs through two distinct mechanisms: histamine- and bradykinin-dependent. Although they respond to distinct treatments, these two potentially life-threatening states present similarly. Poor recognition of the bradykinin-dependent pathway leads to treatment errors in the emergency department (ED), despite the availability of multiple pharmacologic options for hereditary angioedema (HAE) and other forms of bradykinin-induced angioedema. Here, we consider the pathophysiology and clinical features of bradykinin-induced angioedema, and we present a systematic literature review exploring the effectiveness of the available therapies for managing such cases.
Methods
PubMed searches using ‘emergency’, ‘bradykinin’ and various therapeutic product names identified studies reporting the efficacy of treatments for bradykinin-induced angioedema in the ED setting. In all, 22 studies met prespecified criteria and are analysed here.
Findings
Whereas histamine-induced angioedema has a faster onset and often presents with urticaria, bradykinin-induced angioedema is slower in onset, with greater incidence of abdominal symptoms. Acute airway angioedema in the ED should initially be treated with anaphylactic protocols, focusing on airway management and treatment with epinephrine, antihistamine and systemic steroids. Bradykinin-induced angioedema should be considered if this standard treatment is not effective, despite proper dosing and regard of beta-adrenergic blockade. Therapeutics currently approved for HAE appear as promising options for this and other forms of bradykinin-induced angioedema encountered in the ED.
Conclusion
Diagnostic algorithms of bradykinin-induced angioedema should be followed in the ED, with early use of approved therapies to improve patient outcomes.
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