Drug-associated hypertensive crisis: a disproportionality analysis of the FAERS database

By using the FAERS database, we aim to identify and assess risk signals of adverse drug events (ADEs) potentially causing hypertensive crisis, to inform clinical drug management and promote rational drug use. All statistics were extracted from FAERS by four disproportional methods, which were reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and empirical Bayesian geometric mean (EBGM). These four methods were performed to identify hypertensive crisis-related adverse events (AEs) from FAERS. The Weibull shape parameter test was employed to perform a time to onset (TTO) analysis. From the first quarter of 2004 to the second quarter of 2025, a total of 10,281 drug-related hypertensive crisis reports were recorded. A total of 916 drugs were identified as having potential risk signals. The highest incidence of populations related to hypertensive crisis AEs was 37.9% in the 18-65 age group. Among the top 5 drugs with the highest number of reported drug-associated hypertensive crisis events, amlodipine (288 cases) ranked first. Ramipril (282 cases) and valsartan (192 cases) ranked as the second and third medications, respectively. The top 5 drugs associated with the risk of hypertensive crisis under the ROR algorithm were amlodipine perindopril (ROR = 136.64), methyl aminolevulinate (ROR = 122.78), tranylcypromine (ROR = 105.15), rifapentine (ROR = 39.46), and amiloride hydrochlorothiazide (ROR = 39.36). Additionally, the timing of AEs related to hypertensive crisis revealed that the highest incidence (30.69%) was observed within 3 days. The median TTO and interquartile range (IQR) for the top three positive drugs with the highest reported number were as follows: amlodipine 362 (48, 721); ramipril 320 (51, 572); and valsartan 89 (7, 468). These drugs exhibited an early failure type. Our study showed that numerous medications carry potential risks for drug-associated hypertensive crisis. Further investigation is required to establish causality and inform clinical decision-making.