From the Guidelines
Angioedema from ACE inhibitors can occur at any time during treatment, with delays ranging from hours to years after starting the medication, and if a patient develops angioedema while on an ACE inhibitor, the medication should be discontinued immediately and permanently avoided. This delayed reaction occurs because ACE inhibitors block the breakdown of bradykinin, leading to its accumulation over time, as noted in the study by 1. Individual genetic variations in bradykinin metabolism and environmental triggers can influence when symptoms appear.
While most reactions occur within the first week, approximately 25% of cases develop after 6 months of therapy, and some cases have been reported even after years of uneventful use, as seen in the guidelines provided by 1. Alternative medications such as angiotensin receptor blockers (ARBs), calcium channel blockers, or thiazide diuretics should be considered instead, though ARBs should be used cautiously as there is a small risk (about 0-10%) of cross-reactivity, as mentioned in the study by 1.
Some key points to consider include:
- The risk of angioedema with ACE inhibitors is higher in certain populations, such as African Americans, as noted in 1.
- Patients with a history of angioedema during treatment with an ACE-I might be at increased risk if switched to aliskiren as an alternative antihypertensive agent, as seen in the study by 1.
- The decision to switch to an ARB or to aliskiren when suspending an ACE-I because of angioedema should be considered in the context of a careful assessment of potential harm (recurrent angioedema) compared with benefit (therapeutic need for angiotensin/renin inhibition) and involve the patient in the decision-making process, as recommended by 1.
Patients with ACE inhibitor-induced angioedema should carry medical identification indicating this reaction, and emergency treatment may include antihistamines, corticosteroids, epinephrine, or in severe cases, intubation for airway protection, as suggested by 1 and 1.
From the Research
Angioedema Delay on ACE Inhibitors
- Angioedema is a complication that has been reported in up to 1.0% of individuals taking angiotensin-converting enzyme inhibitors (ACE-Is) 2.
- The onset of angioedema can occur anywhere from hours to several years after initiation of therapy with ACE-Is 2.
- The underlying pathophysiology of ACE-I-induced angioedema is incompletely understood, but is considered to be due in large part to excess bradykinin 2, 3, 4.
- Angioedema occurs more frequently in African Americans, smokers, women, older individuals, and those with a history of drug rash, seasonal allergies, and use of immunosuppressive therapy 3.
- Treatment modalities include antihistamines, steroids, and epinephrine, as well as endotracheal intubation in cases of airway compromise 3, 5.
- Patients with a history of ACE-I-induced angioedema should not be re-challenged with this class of agents, as there is a relatively high risk of recurrence 3, 4.
Delay in Onset of Angioedema
- The delay in onset of angioedema after starting ACE inhibitors can range from hours to several years 2.
- The exact mechanism of this delay is not fully understood, but it is thought to be related to the accumulation of bradykinin over time 4.
- Genetic predisposition may also play a role in the delay, with some individuals being more susceptible to ACE-I-induced angioedema due to genetic variations in bradykinin metabolism and action 4.
Management of Angioedema
- The primary focus for the treatment of ACE-I-induced angioedema is airway management 2.
- In the absence of high-quality evidence, no specific medication therapy is recommended for its treatment 2.
- However, some studies have shown efficacy of bradykinin antagonists, such as icatibant, in treating ACE-I-induced angioedema 5.
- Fresh frozen plasma or C1 inhibitor concentrate infusion may also be effective in some cases 4, 5.