Increasing risk of hemorrhage following concurrent use of <i>Salvia miltiorrhiza</i> and oral anticoagulants: a retrospective self-controlled case series study

Background: There has been a growing trend of combining traditional Chinese medicine and Western medicine, but the safety of co-prescribing Salvia miltiorrhiza (Danshen) and anticoagulants remains uncertain. Objectives: This study aimed to evaluate the bleeding risk following the concurrent prescribing of S. miltiorrhiza and anticoagulants in a real-world setting. Design: A self-controlled case series study was conducted. Methods: This study used the Chang Gung Research Database to identify adult patients co-prescribed oral anticoagulants and S. miltiorrhiza , and having records of bleeding events. Bleeding events included any bleeding event (gastrointestinal, intracranial, or urogenital bleeding) and major bleeding events (hemorrhages requiring hospitalization or transfusion). Exposure periods were defined as days of concurrent prescribing of S. miltiorrhiza and anticoagulants, while control periods included days of anticoagulant use without S. miltiorrhiza . Conditional Poisson regression was applied to estimate bleeding risk during exposure periods relative to control periods, and results were presented as adjusted incidence rate ratio (aIRR) and 95% confidence interval (95%CI). Results: Among 525 patients receiving both medications, 146 experienced bleeding events. The risk of any bleeding increased significantly during days 1–14 (aIRR: 3.98; 95% CI: 3.29–4.77) and days 15–28 (aIRR: 3.99; 95% CI: 3.23–4.79) after concurrent prescribing of S. miltiorrhiza and anticoagulants. Elevated risks of gastrointestinal bleeding (aIRR: 3.79; 95% CI: 2.95–4.53) and intracranial hemorrhage (aIRR: 3.59; 95% CI: 2.79–5.03) were observed within the first 14 days. Conclusion: Concurrent use of S. miltiorrhiza and anticoagulants significantly increased bleeding risk, particularly during the first 28 days of coadministration. These findings highlight the need for careful monitoring during the initial period of combined therapy.