Oral Anticoagulant and Proton Pump Inhibitor Cotherapy and GI Bleeding

Study Questions:

What is the incidence of hospitalization for upper gastrointestinal (GI) tract bleeding in patients using oral anticoagulants with and without proton pump inhibitor (PPI) therapy?


The authors performed a retrospective cohort study of Medicare recipients between January 2011 and September 2015. Patients taking any oral anticoagulants with or without PPI coprescription were identified. The main outcome was the adjusted hospitalization rate for upper GI bleed.


Among 1,643,123 patients taking oral anticoagulants, over 651,427 patient-years of follow-up, the adjusted incidence of hospitalization for upper GI bleed was 115/10,000 person-years (95% confidence interval, 112-118) for patients without PPI coprescription. Adjusted incidence of hospitalization was higher among patients using rivaroxaban (144/10,000 person-years) as compared to apixaban (73/10,000 person-years), dabigatran (120/10,000 person-years), and warfarin (113/10,000 person-years). The risk of hospitalization for upper GI bleed was lower among patients prescribed PPI as compared to no PPI prescription across all oral anticoagulants.


The authors concluded that hospitalization for upper GI bleeding was highest among patients prescribed rivaroxaban and that the incidence of hospitalization was significantly lowered when PPI therapy was coprescribed.


This study highlights two important findings. Consistent with some prior reports, the risk of GI bleeding appears higher among patients prescribed rivaroxaban as compared to other oral anticoagulants (including apixaban and warfarin). Second, use of PPI therapy may help to reduce the incidence of hospitalization for upper GI bleed among patients taking oral anticoagulants, including the direct oral anticoagulants. The benefit of PPI therapy was more pronounced among patients at higher risk of GI bleeding, including those with prior GI bleeding and patients taking medications that increase GI bleeding risk. Clinicians prescribing oral anticoagulant therapy should routinely assess for GI bleed risk and consider prescribing PPI therapy to patients at increased risk.

Clinical Topics: Anticoagulation Management, Prevention

Keywords: Anticoagulants, Gastrointestinal Hemorrhage, Medicare, Proton Pump Inhibitors, Upper Gastrointestinal Tract, Risk, Secondary Prevention, Vascular Diseases, Warfarin

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