Key result
Concomitant SSRIs with antithrombotics link to ~34% higher gastrointestinal bleeding risk.
Why the study?
Standard bleeding risk scores (HAS-BLED, ORBIT) do not account for changes in concomitant pharmacotherapy, limiting their predictive value for gastrointestinal bleeding in comorbid patients receiving antithrombotic therapy. This review sought to summarize the pharmacokinetic and pharmacodynamic mechanisms of drug-drug interactions involving antithrombotic agents and substantiate bleeding risk reduction strategies.
Do drug-drug interactions between antithrombotic agents and concomitant medications increase the risk of gastrointestinal bleeding in comorbid patients?
Do drug-drug interactions between antithrombotic agents and concomitant medications increase the risk of gastrointestinal bleeding in comorbid patients?
Severe gastrointestinal bleeding in patients on antithrombotic therapy is heavily driven by polypharmacy and drug-drug interactions, necessitating avoidance of NSAIDs, renal dose adjustment of DOACs, and selective gastroprotection with pantoprazole or rabeprazole.
Answers are grounded in this paper and cite their sources.
Screen antithrombotic patients for interacting drugs to lower GI bleeding; extends standard scores by incorporating polypharmacy effects.
Background . In comorbid patients receiving antithrombotic therapy, drug–drug interactions (DDIs) are among the key modifiable risk factors for gastrointestinal bleeding (GIB). However, standard bleeding risk scores (HAS‑BLED, ORBIT) do not account for changes in concomitant pharmacotherapy, which limits their predictive value. Objective . To summarize the available evidence on pharmacokinetic and pharmacodynamic mechanisms underlying DDIs between antithrombotic agents and other drugs that contribute to GIB, and to substantiate strategies for reducing bleeding risk. Methods . A literature search was performed in PubMed and eLIBRARY.RU for publications from 2020 to 2026. Full‑text systematic reviews, meta‑analyses, and cohort studies published in Russian or English were included. Interactions involving direct oral anticoagulants (DOACs), warfarin, and antiplatelet agents mediated by P‑glycoprotein (P‑gp), cytochrome P450 isoenzymes, and synergistic hemostatic effects were analyzed. Results . Inhibitors of P‑gp and CYP3A4 (amiodarone, verapamil, ketoconazole) substantially increase DOAC exposure: the area under the concentration–time curve (AUC) of dabigatran increases 2.5‑fold with verapamil, and that of rivaroxaban by 158 % with ketoconazole. CYP2C19 inhibitors (omeprazole, esomeprazole) induce clopidogrel phenoconversion, associated with a higher rate of cardiovascular events. Concomitant NSAID use increases GIB risk 3.01‑fold, SSRIs by 34 % (OR = 1.34), and systemic glucocorticoids by 33 % (OR = 1.33). Drug‑related problems are identified in more than 75 % of cardiac patients. Conclusion . Severe bleeding events are more often linked to polypharmacy and DDIs than to the isolated effect of antithrombotic drugs. Prevention requires individualized pharmacotherapy management, dose adjustment of DOACs based on renal function, avoidance of NSAIDs, and gastroprotection with proton pump inhibitors that have minimal CYP2C19 affinity (pantoprazole, rabeprazole).
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Teplova et al. (2026) conducted a review in Gastrointestinal bleeding in comorbid patients receiving antithrombotic therapy. Concomitant pharmacotherapy (P-gp/CYP3A4 inhibitors, CYP2C19 inhibitors, NSAIDs, SSRIs, systemic glucocorticoids) with antithrombotic agents vs. Isolated antithrombotic therapy without interacting drugs was evaluated on Gastrointestinal bleeding (OR 1.34 (for SSRIs); OR 1.33 (for glucocorticoids); 3.01-fold increase (for NSAIDs)). Concomitant NSAIDs, SSRIs (OR 1.34), and glucocorticoids (OR 1.33) with antithrombotics increase gastrointestinal bleeding risk, while P-gp/CYP3A4 inhibitors raise DOAC exposure up to 2.5-fold.
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