Risk of angioedema and thrombolytic therapy among stroke patients: An analysis of data from the FDA Adverse Event Reporting System database

Hunong Xiang; Yu Ma; Xiaochao Luo; Jian Guo; Minghong Yao; Yanmei Liu; Ke Deng; Xin Sun; Ling Li

doi:10.1016/j.neurot.2024.e00474

Risk of angioedema and thrombolytic therapy among stroke patients: An analysis of data from the FDA Adverse Event Reporting System database

Neurotherapeutics. 2024 Oct 30:e00474. doi: 10.1016/j.neurot.2024.e00474. Online ahead of print.

Authors

Hunong Xiang¹, Yu Ma¹, Xiaochao Luo¹, Jian Guo², Minghong Yao¹, Yanmei Liu¹, Ke Deng¹, Xin Sun³, Ling Li⁴

Affiliations

¹ Department of Neurology and Chinese Evidence-based Medicine Center, West China Hospital, Sichuan University, Chengdu, 610041, China; NMPA Key Laboratory for Real World Data Research and Evaluation in Hainan, Chengdu, 610041, China; Sichuan Center of Technology Innovation for Real World Data, Chengdu, 610041, China.
² Department of Neurology, West China Hospital, Sichuan University, Chengdu, 610041, China.
³ Department of Neurology and Chinese Evidence-based Medicine Center, West China Hospital, Sichuan University, Chengdu, 610041, China; NMPA Key Laboratory for Real World Data Research and Evaluation in Hainan, Chengdu, 610041, China; Sichuan Center of Technology Innovation for Real World Data, Chengdu, 610041, China. Electronic address: [email protected].
⁴ Department of Neurology and Chinese Evidence-based Medicine Center, West China Hospital, Sichuan University, Chengdu, 610041, China; NMPA Key Laboratory for Real World Data Research and Evaluation in Hainan, Chengdu, 610041, China; Sichuan Center of Technology Innovation for Real World Data, Chengdu, 610041, China. Electronic address: [email protected].

PMID: 39482180
DOI: 10.1016/j.neurot.2024.e00474

Abstract

The angioedema risk may vary among stroke patients receiving different thrombolytic agents. This study aimed to investigate the angioedema risk associated with different thrombolytic agents and to identify associated risk factors. We conducted a large-scale retrospective pharmacovigilance study using the FDA Adverse Event Reporting System (FAERS) database. Stroke patients receiving thrombolytic therapy (i.e., alteplase or tenecteplase) were identified, and the associations with angioedema were explored using disproportionality analysis and time-to-onset analysis. Additionally, we used adapted Bradford Hill criteria to confirm these associations. Risk factors for angioedema were explored using stepwise logistic regression. A total of 17,776 stroke patients were included, with 2973 receiving alteplase and 278 receiving tenecteplase. Disproportionality analysis revealed that angioedema might be associated with alteplase (adjusted ROR [aROR] 5.13 [95 % CI, 4.55-5.79]) or tenecteplase (aROR 2.72 [95 % CI, 1.98-3.67]). The adapted Bradford Hill criteria suggested a probable causal relationship between alteplase and angioedema, whereas there was insufficient evidence of a probable causal relationship with tenecteplase. Multivariate analysis revealed that ACE-inhibitors use (aROR 9.73 [95 % CI, 7.29-12.98]), female sex (aROR 1.38 [95 % CI, 1.13-1.67]) and hypertension (aROR 2.11 [95 % CI, 1.52-2.92]) were significant risk factors for angioedema among alteplase-treated stroke patients. Our study suggested that alteplase is associated with a greater risk of angioedema among stroke patients, but there is insufficient evidence to support an association between tenecteplase and angioedema. Clinicians should be vigilant for this potentially life-threatening complication, particularly in patients with identified risk factors. It is also prudent to consider tenecteplase as an alternative, if available.

Keywords: Alteplase; Angioedema; FAERS; Tenecteplase.