Tian Xiaojiang, Wang Xiaoli, Wang Kejing, Chen Lin
Objective To systematically understand the occurrence of dabigatran etexilate-related bleeding events, and provide reference for clinical safe drug use. Methods Reports on adverse event (AE) and bleeding event, in which dabigatran etexilate was considered as the first suspected drug, in the US Food and Drug Administration Adverse Event Reporting System (FAERS) from January 2004 to April 2019 were extracted. According to the preferred system organ class (SOC) and preferred term (PT) from terminology of adverse drug reactions in Medical Dictionary for Regulatory Activities, the bleeding event reports were classified, and the patient′s age, gender, drug dosage and AE occurrence were extracted. Based on SOC and PT respectively, the signals of dabigatran etexilate-related hemorrhage were detected using 3 methods inclu- ding reporting odds ratio (ROR), proportional reporting ratio (PRR), and Bayesian confidence propagation neural network (BCPNN). If the results were all positive using the 3 methods, it would be considered as the suspected AE signal. Results A total of 56-501 AE reports with dabigatran etexilate as the primary suspected drug were collected, in which 19-737 (34.93%) reports were about bleeding events. Among the 19-737 patients, 9-687 (49.08%) were male, 9-790 (49.60%) were female, and 260 (1.32%) were with unknown gender; their ages ranged from 18 to 95 years, 2 742 (13.89%) patients were <75 years old, 15-051 (76.26%) were ≥75 years old, and 1-944 (9.85%) were with unknown age; the dose of dabigatran etexilate was 110-mg once daily in 416 patients (2.11%), 110-mg twice daily in 2 346 patients (11.89%), 150-mg once daily in 525 patients (2.66%), 150-mg twice daily in 402 patients (20.33%), and unknown in 12-438 patients (63.02%); 9-242 patients (46.83%) developed serious bleeding events, and 3-260 patients (16.52%) died. The SOCs with positive signals detected using the 3 methods were gastrointestinal disorders(14-382 cases,72.87%), central nervous disorders (3-216 cases,16.29%), renal and urinary disorders (7.41%, 1-462 cases), skin and subcutaneous tissue disorders (2.92%, 576 cases), and eye disorders (0.51%, 101 cases). The top 3 SOCs with higher signal intensities were gastrointestinal disorders, renal and urinary disorders, and central nervous disorders. A total of 32 PTs with positive signals were detected using the 3 methods. Of them, 12 PTs were positive in gastrointestinal disorders, and the top 5 PTs with higher signal intensities were lower gastrointestinal bleeding, gastrointestinal bleeding, upper gastrointestinal bleeding, chronic gastrointestinal bleeding, and melena; 2 PTs were positive in renal and urinary disorders, in which the urinary tract hemorrhage was with higher intensity; 11 PTs were positive in central nervous disorders, and the top 5 PTs with higher signal intensities were intracranial hemorrhage, intracranial hematoma, hemorrhagic stroke, subdural hemorrhage, and epidural hemorrhage; 4 PTs were positive in skin and subcutaneous tissue disorders, and the signal intensity of subcutaneous hemorrhage ranked the first; 2 PTs were positive in eye disorders, in which the conjunctival hemorrhage was with higher intensity. Conclusions Bleeding is more severe in dabigatran etexilate-related AEs, and gastrointestinal bleeding is more common. Patients with age ≥75 years have a higher risk of bleeding, which should be paid attention to in clinic.
