Abstract

A DISPROPORTIONALITY ANALYSIS OF ANGIOEDEMA WITH TISSUE PLASMINOGEN ACTIVATORS (ALTEPLASE, RETEPLASE AND TENECTEPLASE) BASED ON FAERS DATABASE

Farzana Nazar*, Niveena Varghese, Fida Firdouse and Emily James

Abstract

Background: Tissue plasminogen activator (tPAs) biochemically a serine protease (enzymes that cleave peptide bonds in proteins). It is considered as essential component for the dissolution of blood clots. It has its catalysing ability in the full conversion of plasminogen to plasmin, the primary enzyme involved in dissolving blood clots. Ischemic stroke, Myocardial infarction, Pulmonary embolism, Deep Vein Thrombosis are the main indications of tPAs. However, these medications have been associated with increased occurrence of angioedema. The objective of this study is to investigate potential safety signals for tPAs with angioedema using disproportionality analysis enscripted in the FDA Adverse Even Reporting System (FAERS) database. Research design and methods: The study retrospectively investigated case/non-case analysis using Openvigil 2.1-MedDRA-v24 (2004Q1 to 2022Q4). The preferred term used was ‘angioedema’ and the drugs included were Alteplase, Tenecteplase and Reteplase. Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), and Information Component (IC) were used to quantify the disproportionality and measure its signal strength. Results: Overall 19676 AE reports related to tPAs were identified, of which 790 reports (alteplase − 761, tenecteplase − 33, and reteplase − 0) associated with angioedema were obtained from FAERS. On analysis, alteplase had greater signal strength for age group of 65–100 years while tenecteplase had greater signal strength for age group of 0-18 years. In gender categorization, alteplase showed greater signal strength for females while tenecteplase showed greater signal strength for males. Conclusions: Our study identified signals for angioedema with alteplase and tenecteplase.

Keywords: Disproportionality Analysis, OpenVigil, tPAs, Angioedema, FAERS.