Abstract: Objective To analyze the adverse reaction signals of nintedanib using the food and drug administration adverse event reporting system(FAERS)database. Methods Cases reported in the FAERS database from the July of 2014 to September of 2023 with nintedanib as suspected cause of adverse drug events were collected. After standardization of the WHO adverse drug reaction terminology, the reporting odds ratio method(ROR), proportional reporting ratio method(PRR)and multinomial gamma Posson distribution(MGPS)methods were used for adverse reaction signal detection. Results In total, 17,547 adverse reaction case reports listing nintedanib as the primary suspected drug were extracted from the FAERS database. Most patients were male(9,709 cases, 55.3%). The age mainly ranged from 65 to 85(8,856 cases, 50.5%). The majority of cases were reported from United States(10,209 cases, 58.2%), and the largest number of cases was reported in 2022(2,876 cases, 17.46%). In total, 24 cardiovascular adverse reaction signals were obtained through the ROR, PRR and MGPS methods, among which the RORs were highest for paroxysmal arrhythmia, aortic rupture, aortic valve calcification, heart valve surgery, and cardiac catheterization were ranked higher. The reported adverse reactions included hypertension(385 cases), elevated blood pressure(291 cases), myocardial infarction(182 cases), hypotension(175 cases), and atrial fibrillation(142 cases). The adverse reaction signals were consistent with the excavation signals, although adverse reactions such as aortic rupture, aortic valve calcification, and atrial fibrillation were not listed in the drug instructions. Conclusion Drug evaluation should be performed before the clinical use of nintedanib, especially for high-risk patients with cardiovascular diseases such as vascular disease, ischemic heart disease,and arrhythmia. Monitoring using electrocardiogram, electrolyte measurement, cardiac ultrasound, and other techniques should be strengthened, and clinicians should pay attention to adverse reactions beyond those listed in the instructions are included to ensure the safe use of this drug.

Key words: Nintedanib, Adverse event reporting system, Real-world research, Data mining, Cardiovascular adverse reaction signals