Gastroprotection in combined antithrombotic therapy: A systematic review

Combined anticoagulant and antiplatelet therapy substantially increase the risk of gastrointestinal (GI) bleeding, particularly in high-risk populations requiring dual or triple antithrombotic regimens. Appropriate gastroprotective strategies remain essential to balance thrombotic and bleeding risks. The objective of this study is to systematically evaluate the effectiveness, indications, and safety of gastroprotective strategies in patients receiving combined anticoagulant and antiplatelet therapy, with and without established gastrointestinal bleeding. Evidence review : A systematic literature search of PubMed/MEDLINE, Embase, and Cochrane Library databases was conducted for studies published between January 2005 and December 2025. Randomized clinical trials, meta-analyses, cohort studies, and major guideline recommendations assessing gastroprotection in patients receiving anticoagulant and antiplatelet therapy were included. Studies evaluating proton pump inhibitors (PPIs), histamine-2 receptor antagonists, and risk-modifying strategies were prioritized. Risk of bias was assessed using Cochrane and Newcastle–Ottawa tools. Evidence synthesis followed PRISMA guidelines. Findings : Among 5,438 identified records, 112 studies met inclusion criteria. Proton pump inhibitors significantly reduced upper GI bleeding risk in patients receiving combined antithrombotic therapy (relative risk reductions ranging from 30% to 60%). Patients with prior GI bleeding, advanced age, triple therapy exposure, and concomitant nonsteroidal anti-inflammatory drug use exhibited the highest bleeding risk. Direct oral anticoagulants demonstrated variable GI bleeding risk profiles compared with vitamin K antagonists, particularly when combined with antiplatelets. Conclusions and relevance : Gastroprotective therapy, particularly with proton pump inhibitors, is strongly supported in high-risk patients receiving combined anticoagulant and antiplatelet therapy. Risk stratification and individualized therapy are essential to optimize safety and clinical outcomes.