Is there any data on alteplase causing angioedema?

Comment by InpharmD Researcher

Orolingual angioedema (OA) is identified to be a rare but potentially serious complication with cases mainly occurring during or two hours after alteplase administration. Most incidences are managed by symptomatic treatment. Independent risk factors for developing OA may include female sex and ACE-inhibitor use prior to alteplase treatment.

Background

Angioedema after alteplase administration is mainly reported as orolingual angioedema (OA), identified as swelling of the tongue and upper lip. Serious cases can lead to obstruction of the airway. Most incidents have been treated with symptomatic therapy. The mechanism behind alteplase-associated OA is not yet known but could possibly be linked to the upregulation of bradykinin. [1], [2], [3], [4], [5]

A meta-analysis gathered evidence from 1950 to 2012 on the incidence of OA after alteplase administration for acute ischemic stroke. All evidence was from case reports or case series, totaling 41 cases of OA. The incidence of OA after alteplase administration was found to be between 1.70% and 5.88% and 24 of 41 patients (58.5%) were taking an ACE inhibitor. Risk for OA were not significantly higher in those taking ACE-inhibitor (risk ratio 1.4667; 95% CI 0.8978 to 2.396; p=0.1261) or angiotensin II inhibitors (risk ratio 4.1481; 95% CI 0.2287 to 75.2386; p=0.3360). Most incidences were mild and managed with anti-inflammatory medications, however, one patient developed fatal ventricular tachycardia from OA. [1]

A retrospective study and literature review found an incidence rate of alteplase-associated OA to be around 0.2 to 5.1% in stroke patients. Eight of 236 (3.4%) patients with acute stroke developed alteplase-associated OA within the author's single-institution study. All symptoms were resolved with treatment with no greater complications reported beyond respiratory distress. Five of 8 patients were taking an ACE inhibitor. [2]

A retrospective case-cohort study analyzed 659 patients with acute ischemic stroke treated with alteplase. 32 (4.9%) developed OA with independent predictors for OA occurrence revealed to be female sex (odds ratio [OR] 5.47; 95% CI 1.98 to 15.10) and use of ACE-inhibitor (OR 3.87; 95% CI 1.71 to 8.75). The author's own literature review also identified a greater occurrence of alteplase-associated OA in women and those taking ACE-I. Another retrospective study specific to the Asian population found that ACE-inhibitors were the highest risk factor among 559 patients. Although, only 5 of 559 (0.89%) developed OA, which may indicate the rate of alteplase-associated OA occurs less frequently in the Asian population. The author's separate meta-analysis also observed a high risk of OA in patients taking ACE inhibitors (relative risk [RR] 12.9; 95% CI 4.5 to 37.0). [3], [4]

References:

[1] Yayan J. Onset of Orolingual Angioedema After Treatment of Acute Brain Ischemia with Alteplase Depends on the Site of Brain Ischemia: A Meta-analysis. N Am J Med Sci. 2013;5(10):589-593. doi:10.4103/1947-2714.120794
[2] Correia AS, Matias G, Calado S, Lourenço A, Viana-Baptista M. Orolingual angiodema associated with alteplase treatment of acute stroke: a reappraisal. J Stroke Cerebrovasc Dis. 2015;24(1):31-40. doi:10.1016/j.jstrokecerebrovasdis.2014.07.045
[3] Pinho J, Alves JN, Oliveira L, et al. Orolingual angioedema after thrombolysis is not associated with insular cortex ischemia on pre-thrombolysis CT. J Neurol Sci. 2016;369:48-50. doi:10.1016/j.jns.2016.07.043
[4] Lin SY, Tang SC, Tsai LK, et al. Orolingual angioedema after alteplase therapy of acute ischaemic stroke: incidence and risk of prior angiotensin-converting enzyme inhibitor use. Eur J Neurol. 2014;21(10):1285-1291. doi:10.1111/ene.12472
[5] Bar B, Biller J. Select hyperacute complications of ischemic stroke: cerebral edema, hemorrhagic transformation, and orolingual angioedema secondary to intravenous Alteplase. Expert Rev Neurother. 2018;18(10):749-759. doi:10.1080/14737175.2018.1521723