title: Association of Proton Pump Inhibitors With Reduced Risk of Warfarin-Related Serious Upper Gastrointestinal Bleeding.
abstract: Proton pump inhibitors (PPIs) might reduce the risk of serious warfarin-related upper gastrointestinal bleeding, but the evidence of their efficacy for this indication is limited. A gastroprotective effect of PPIs would be particularly important for patients who take warfarin with antiplatelet drugs or nonselective nonsteroidal anti-inflammatory drugs (NSAIDs), which further increase the risk of gastrointestinal bleeding.
  
  
  
  This retrospective cohort study of patients beginning warfarin treatment in Tennessee Medicaid and the 5% National Medicare Sample identified 97,430 new episodes of warfarin treatment with 75,720 person-years of follow-up. The study end points were hospitalizations for upper gastrointestinal bleeding potentially preventable by PPIs and for bleeding at other sites.
  
  
  
  Patients who took warfarin without PPI co-therapy had 119 hospitalizations for upper gastrointestinal bleeding per 10,000 person-years of treatment. The risk decreased by 24% among patients who received PPI co-therapy (adjusted hazard ratio [HR], 0.76; 95% confidence interval [CI], 0.63-0.91). There was no significant reduction in the risk of other gastrointestinal bleeding hospitalizations (HR, 1.07; 95% CI, 0.94-1.22) or non-gastrointestinal bleeding hospitalizations (HR, 0.98; 95% CI, 0.84-1.15) in this group. Among patients concurrently using antiplatelet drugs or NSAIDs, those without PPI co-therapy had 284 upper gastrointestinal bleeding hospitalizations per 10,000 person-years of warfarin treatment. The risk decreased by 45% (HR, 0.55; 95% CI, 0.39-0.77) with PPI co-therapy. PPI co-therapy had no significant protective effect for warfarin patients not using antiplatelet drugs or NSAIDs (HR, 0.86; 95% CI, 0.70-1.06). Findings were similar in both study populations.
  
  
  
  In an analysis of patients beginning warfarin treatment in Tennessee Medicaid and the 5% National Medicare Sample, PPI co-therapy was associated with reduced risk of warfarin-related upper gastrointestinal bleeding; the greatest reduction occurred in patients also taking antiplatelet drugs or NSAIDs.
authors.affiliation: Department of Health Policy, Vanderbilt University School of Medicine, Nashville, Tennessee. Electronic address: wayne.ray@vanderbilt.edu.
authors.forename: Wayne A
authors.initials: WA
authors.lastname: Ray
authors.affiliation: Department of Medicine, Division of Rheumatology, Vanderbilt University School of Medicine, Nashville, Tennessee; Department of Clinical Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee; Veterans' Administration Tennessee Valley Health Care System, Nashville, Tennessee.
authors.forename: Cecilia P
authors.initials: CP
authors.lastname: Chung
authors.affiliation: Department of Clinical Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee; Department of Medicine, Division of Cardiology, Vanderbilt University School of Medicine, Nashville, Tennessee; Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee.
authors.forename: Katherine T
authors.initials: KT
authors.lastname: Murray
authors.affiliation: Department of Health Policy, Vanderbilt University School of Medicine, Nashville, Tennessee; Veterans' Administration Tennessee Valley Health Care System, Nashville, Tennessee; Department of Gastroenterology, Vanderbilt University School of Medicine, Nashville, Tennessee.
authors.forename: Walter E
authors.initials: WE
authors.lastname: Smalley
authors.affiliation: Department of Health Policy, Vanderbilt University School of Medicine, Nashville, Tennessee.
authors.forename: James R
authors.initials: JR
authors.lastname: Daugherty
authors.affiliation: Department of Biostatistics, Vanderbilt University School of Medicine, Nashville, Tennessee.
authors.forename: William D
authors.initials: WD
authors.lastname: Dupont
authors.affiliation: Department of Medicine, Division of Rheumatology, Vanderbilt University School of Medicine, Nashville, Tennessee; Department of Clinical Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee.
authors.forename: C Michael
authors.initials: CM
authors.lastname: Stein
mesh_terms: D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects; D000925:Anticoagulants / Q000009:adverse effects*; D004359:Drug Therapy, Combination; D005260:Female; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced / Q000517:prevention & control*; D006760:Hospitalization / Q000706:statistics & numerical data*; D006801:Humans; D008297:Male; D008484:Medicaid / Q000706:statistics & numerical data; D006278:Medicare / Q000706:statistics & numerical data; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects; D065840:Protective Factors; D054328:Proton Pump Inhibitors / Q000627:therapeutic use*; D012189:Retrospective Studies; D013714:Tennessee; D014481:United States; D014859:Warfarin / Q000009:adverse effects*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000925:Anticoagulants; D010975:Platelet Aggregation Inhibitors; D054328:Proton Pump Inhibitors; D014859:Warfarin
keywords: Antiplatelet Drugs; Proton-Pump Inhibitor; Warfarin