CoChat
Sign Up
Cited by 222Atrial Fibrillation Management and OutcomesGastrointestinal Bleeding Diagnosis and TreatmentAntiplatelet Therapy and Cardiovascular Diseases

Association of oral anticoagulants and proton pump inhibitor cotherapy with hospitalization for upper gastrointestinal tract bleeding

Open access
Ray, Wayne A., Chung, Cecilia P., Murray, Katherine T., Smalley, Walter E., Daugherty, James R., Dupont, William D., Stein, C. Michael·2018·JAMA
DOI 10.1001/jama.2018.17242PMC PMC6404233
Open this paper in CoChat — free accountOpen PDF

Abstract

Importance: Anticoagulant choice and proton pump inhibitor (PPI) cotherapy could affect the risk of upper gastrointestinal tract bleeding, a frequent and potentially serious complication of oral anticoagulant treatment. Objectives: To compare the incidence of hospitalization for upper gastrointestinal tract bleeding in patients using individual anticoagulants with and without PPI cotherapy, and to determine variation according to underlying gastrointestinal bleeding risk. Design, Setting, and Participants: Retrospective cohort study in Medicare beneficiaries between January 1, 2011, and September 30, 2015. Exposures: Apixaban, dabigatran, rivaroxaban, or warfarin with or without PPI cotherapy. Main Outcomes and Measures: Hospitalizations for upper gastrointestinal tract bleeding: adjusted incidence and risk difference (RD) per 10 000 person-years of anticoagulant treatment, incidence rate ratios (IRRs). Results: There were 1 643 123 patients with 1 713 183 new episodes of oral anticoagulant treatment included in the cohort (mean [SD] age, 76.4 [2.4] years, 651 427 person-years of follow-up [56.1%] were for women, and the indication was atrial fibrillation for 870 330 person-years [74.9%]). During 754 389 treatment person-years without PPI cotherapy, the adjusted incidence of hospitalization for upper gastrointestinal tract bleeding (n = 7119) was 115 per 10 000 person-years (95% CI, 112-118). The incidence for rivaroxaban (n = 1278) was 144 per 10 000 person-years (95% CI, 136-152), which was significantly greater than the incidence of hospitalizations for apixaban (n = 279; 73 per 10 000 person-years; IRR, 1.97 [95% CI, 1.73-2.25]; RD, 70.9 [95% CI, 59.1-82.7]), dabigatran (n = 629; 120 per 10 000 person-years; IRR, 1.19 [95% CI, 1.08-1.32]; RD, 23.4 [95% CI, 10.6-36.2]), and warfarin (n = 4933; 113 per 10 000 person-years; IRR, 1.27 [95% CI, 1.19-1.35]; RD, 30.4 [95% CI, 20.3-40.6]). The incidence for apixaban was significantly lower than that for dabigatran (IRR, 0.61 [95% CI, 0.52-0.70]; RD, -47.5 [95% CI,-60.6 to -34.3]) and warfarin (IRR, 0.64 [95% CI, 0.57-0.73]; RD, -40.5 [95% CI, -50.0 to -31.0]). When anticoagulant treatment with PPI cotherapy (264 447 person-years; 76 per 10 000 person-years) was compared with treatment without PPI cotherapy, risk of upper gastrointestinal tract bleeding hospitalizations (n = 2245) was lower overall (IRR, 0.66 [95% CI, 0.62-0.69]) and for apixaban (IRR, 0.66 [95% CI, 0.52-0.85]; RD, -24 [95% CI, -38 to -11]), dabigatran (IRR, 0.49 [95% CI, 0.41-0.59]; RD, -61.1 [95% CI, -74.8 to -47.4]), rivaroxaban (IRR, 0.75 [95% CI, 0.68-0.84]; RD, -35.5 [95% CI, -48.6 to -22.4]), and warfarin (IRR, 0.65 [95% CI, 0.62-0.69]; RD, -39.3 [95% CI, -44.5 to -34.2]). Conclusions and Relevance: Among patients initiating oral anticoagulant treatment, incidence of hospitalization for upper gastrointestinal tract bleeding was the highest in patients prescribed rivaroxaban, and the lowest for patients prescribed apixaban. For each anticoagulant, the incidence of hospitalization for upper gastrointestinal tract bleeding was lower among patients who were receiving PPI cotherapy. These findings may inform assessment of risks and benefits when choosing anticoagulant agents.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1001/jama.2018.17242

Cites

28 of 28 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • The low incidence of VTE had been reported in prior randomized controlled trials but had not been confirmed in real-world patients with less adherence.

    “It is interesting to note that the overall incidence of VTE was very low in both groups, which had been reported in prior randomized controlled trials (RCTs) but had not been confirmed in real-world patients with less adherence compared with randomized trial participants. 15,16”

    From Systematic review and meta-analysis of the efficacy and safety of apixaban compared to rivaroxaban in acute VTE in the real world (2019) · cites this paper as [15]

    The Results (page unavailable) report upper gastrointestinal bleeding hospitalizations, not VTE incidence. Searches for VTE, randomized trials, and adherence found no passage in our copy addressing whether low VTE incidence seen in trials had been confirmed in less-adherent real-world patients. (LLM, conf=0.76)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

1 of the 29 references couldn’t be matched to a known paper.

Cited by

Sorted by citations

Related

Authors
Ray, W. A., Chung, C. P., Murray, K. T., Smalley, W. E., Daugherty, J. R., Dupont, W. D., & Stein, C. M.
Affiliations
Vanderbilt University (US)
Corresponding author
Ray, Wayne A.
ORCID
Venue
JAMA
Publisher
American Medical Association (AMA)
Published
2018-12-04
Volume
320
Issue
21
Pages
2221
ISSN
  • 0002-9955 (ISSN-L)
  • 0098-7484
DOI
10.1001/jama.2018.17242
PMC
PMC6404233
OpenAlex
W2903247782
Cited by
222
References
29
Citations by year
2026: 15 · 2025: 20 · 2024: 26 · 2023: 27 · 2022: 39 · 2021: 37 · 2020: 31 · 2019: 26 · 2018: 1
FWCI
17.94
Type
journal article
Language
en
Open access
Locations
  • JAMA (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Heart, Lung, and Blood Institute (R01HL114518)
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (K23AR064768)
Topics
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Atrial Fibrillation Management and Outcomes
  • Health Sciences › Medicine › Gastroenterology › Gastrointestinal Bleeding Diagnosis and Treatment
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Antiplatelet Therapy and Cardiovascular Diseases
Keywords
oral anticoagulants, proton pump inhibitors, upper gastrointestinal bleeding, hospitalization, apixaban, dabigatran, rivaroxaban, warfarin, atrial fibrillation, bleeding risk, Medicare beneficiaries, risk difference, incidence rate ratio, bleeding complications, anticoagulant reversal, vitamin K antagonists, direct oral anticoagulants
MeSH terms
Rivaroxaban, Dabigatran, Administration, Oral, Aged, Aged, 80 and over, Anticoagulants, Drug Therapy, Combination, Female, Gastrointestinal Hemorrhage, Hospitalization, Humans, Male, Middle Aged, Pyrazoles, Pyridones, Retrospective Studies, Warfarin, Upper Gastrointestinal Tract, Proton Pump Inhibitors

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review