Journal Article

Association Between Anticoagulants and Interacting Drugs and Risk of Major Bleeding in Nonvalvular Atrial Fibrillation: Case-Control Study in SIDIAP, Catalonia, Spain

Giner-Soriano, M., Carrasco-Ribelles, L.A., Castel Llobet, J., Morros, R., Fernández-García, S., Cereza García, G.

2025

Overview

•We estimated the risk of major hemorrhage in non-valvular atrial fibrillation patients treated with oral anticoagulants and simultaneously exposed to potentially interacting drugs which may enhance this bleeding risk.•Both pharmacodynamic and pharmacokinetic interactions resulted in higher bleeding risk for vitamin K antagonists and for direct oral anticoagulants.•Our study underscores the potential impact of drug-drug interactions on cerebral and gastrointestinal bleeding risk in anticoagulated patients.•Proactive strategies, such as risk stratification or proton-pump inhibitors use, may improve patient safety by means of optimizing oral anticoagulants therapy. Interactions with anticoagulants causing an increase in their effect may potentially enhance the bleeding risk. We aimed to analyze the risk of major hemorrhage in anticoagulated patients simultaneously exposed to potentially interacting drugs which may enhance the bleeding risk. Case-control study nested in a cohort of anticoagulated patients in 2011–2020. Cases were all people hospitalized for a major hemorrhage (cerebral or gastrointestinal), matched to individuals without bleeding. The index date was the day of hospital admission for cases and the same date for the matched controls. Data sources: SIDIAP database, containing information from primary health care electronic records, and the database of diagnoses at hospital discharge in Catalonia, Spain. We analyzed exposure to interacting drugs during 3 months prior to the index date. The association between hemorrhage and exposure to interacting drugs was calculated through multivariate logistic regression models. We included 2,811 cases (77.9% cerebral and 22.1% gastrointestinal hemorrhages), matched to 28,054 controls. We found association between hemorrhage in patients receiving vitamin K antagonists (OR 1.30, 95% CI 1.16–1.47). All types of interactions resulted in higher bleeding risk for all anticoagulants. Proton pump inhibitors were found protective for gastrointestinal (OR 0.55, 95% CI 0.46–0.65) but not for cerebral bleeding (OR 1.18, 95% CI 1.08-1.30). We estimated the risk of major hemorrhage in anticoagulated patients simultaneously exposed to potentially interacting drugs which may enhance bleeding risk. Our study underscores the potential impact of interactions on cerebral and gastrointestinal bleeding risk in anticoagulated patients.

• Publisher: Elsevier Inc,Elsevier Limited
• Subject: Aged / Aged, 80 and over / Antagonist drugs / Anticoagulants / Anticoagulants - administration & dosage / Anticoagulants - adverse effects / Atrial Fibrillation - drug therapy / Bleeding / Bleeding risk / Cardiac arrhythmia / Case-Control Studies / Cerebral hemorrhage / Cerebral Hemorrhage - chemically induced / Cerebral Hemorrhage - epidemiology / Databases, Factual / Drug Interactions / Drug-drug interaction / Female / Gastrointestinal hemorrhage / Gastrointestinal Hemorrhage - chemically induced / Gastrointestinal Hemorrhage - epidemiology / Health risks / Hemorrhage / Hemorrhage - chemically induced / Hemorrhage - epidemiology / Hospitalization / Humans / Internal Medicine / Male / Middle Aged / Oral anticoagulants / Patients / Primary care / Proton pump inhibitors / Proton Pump Inhibitors - adverse effects / Regression analysis / Risk Factors / Sociodemographics / Spain - epidemiology / Stroke / Vitamin K / Vitamin K - antagonists & inhibitors