Angioedema risk of thrombolytics: an integrated assessment using disproportionality analysis of the USFDA adverse...

Thrombolytic therapy is linked to angioedema, a serious adverse event, with higher risk when co-administered with renin-angiotensin-aldosterone system inhibitors (RAAS-i), particularly ACE inhibitors. However, this interaction remains incompletely characterized.

A multi-modal analysis: (1) USFDA Adverse Event Reporting System (AERS) disproportionality analysis including reporting odds ratio (ROR); (2) case report review; and (3) meta-analysis and trial sequential analysis of observational studies was performed. Drug interactions were evaluated using multiplicative models. Primary outcomes were mortality and life-threatening events.

Among 521 USFDA AERS reports, disproportionality signals were noted for alteplase (ROR: 3.1) and tenecteplase (ROR 2.85); and signal strength increased with RAAS-i co-administration. Mortality rates were comparable between thrombolytic monotherapy and thrombolytic - RAAS-i combination. Meta-analysis (24 studies; n = 3,007) confirmed increased risk with RAAS-i (OR: 3.12; 95% CI: 2.01-4.85). Case review (n = 60) showed mainly orofacial presentation (n = 59) within 3 hours, with 42 receiving RAAS-i and 16 requiring advanced airway management.

This analysis suggests a consistent association increased angioedema risk with thrombolytic-RAAS-i combination therapy. Findings underscore the importance of careful risk assessment and monitoring in patients receiving RAAS-i therapy, especially those on ACEIs.