Online citations, reference lists, and bibliographies.

Association Of Oral Anticoagulants And Proton Pump Inhibitor Cotherapy With Hospitalization For Upper Gastrointestinal Tract Bleeding

W. A. Ray, Cecilia P Chung, Katherine T. Murray, Walter E. Smalley, James R. Daugherty, William D. Dupont, Charles Michael Stein
Published 2018 · Medicine
Cite This
Download PDF
Analyze on Scholarcy
Share
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.
This paper references
10.1002/pds.3377
Disease risk score as a confounder summary method: systematic review and recommendations.
Mina Tadrous (2013)
10.1093/aje/kwr143
Performance of disease risk scores, propensity scores, and traditional multivariable outcome regression in the presence of multiple confounders.
Patrick G. Arbogast (2011)
Real-World Use of Apixaban for Stroke Prevention in Atrial Fibrillation
Marco Proietti (2018)
10.1097/EDE.0b013e31815be000
Adjustment for multiple cardiovascular risk factors using a summary risk score.
Patrick G. Arbogast (2008)
10.1136/bmj.k2505
Risks and benefits of direct oral anticoagulants versus warfarin in a real world setting: cohort study in primary care
Yana Vinogradova (2018)
10.1007/s11096-016-0299-0
Methods to control for unmeasured confounding in pharmacoepidemiology: an overview
Md. Jamal Uddin (2016)
10.1002/pds.3231
Role of disease risk scores in comparative effectiveness research with emerging therapies.
Robert J Glynn (2012)
10.1053/j.gastro.2015.05.002
Prevention of Dabigatran-Related Gastrointestinal Bleeding With Gastroprotective Agents: A Population-Based Study.
Esther Chin Chi Chan (2015)
10.1016/j.cjca.2017.06.001
Rationale, Design and Baseline Characteristics of Participants in the Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) Trial.
Jackie Bosch (2017)
10.1053/j.gastro.2016.12.018
Gastrointestinal Safety of Direct Oral Anticoagulants: A Large Population-Based Study.
Neena Susan Abraham (2017)
10.1053/j.gastro.2017.02.027
Gastrointestinal Bleeding and Direct Oral Anticoagulants Amongst Patients With Atrial Fibrillation in the "Real World".
Michał Mazurek (2017)
10.1016/j.cjca.2013.04.002
Importance of pharmacokinetic profile and variability as determinants of dose and response to dabigatran, rivaroxaban, and apixaban.
Inna Y. Gong (2013)
10.1002/pds.2109
An automated database case definition for serious bleeding related to oral anticoagulant use.
Andrew Thomas Cunningham (2011)
10.1136/bcr-2013-009139
Severe necrotic oesophageal and gastric ulceration associated with dabigatran
Saurabh Singh (2013)
10.1111/j.1538-7836.2011.04498.x
Population pharmacokinetic analysis of the oral thrombin inhibitor dabigatran etexilate in patients with non-valvular atrial fibrillation from the RE-LY trial.
K-H Liesenfeld (2011)
Dabigatran versus warfarin in patients with atrial fibrillation.
Leon Poller (2009)
10.1016/j.ijcard.2016.03.178
Dabigatran-induced esophagitis: A frequently overlooked adverse effect.
Nixiao Zhang (2016)
10.3109/00365528909091254
Omeprazole in the long-term management of patients with acid-related diseases resistant to ranitidine.
G H Brunner (1989)
10.1093/aje/kwg231
Evaluating medication effects outside of clinical trials: new-user designs.
W. A. Ray (2003)
10.1016/S0140-6736(13)62343-0
Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials
Christian T. Ruff (2014)
10.1016/j.jacc.2013.07.104
The effect of dabigatran plasma concentrations and patient characteristics on the frequency of ischemic stroke and major bleeding in atrial fibrillation patients: the RE-LY Trial (Randomized Evaluation of Long-Term Anticoagulation Therapy).
Paul A. Reilly (2014)
10.1160/TH17-01-0068
Effectiveness and safety of apixaban versus warfarin in non-valvular atrial fibrillation patients in “real-world” clinical practice
Xiaoyan Li (2017)
10.1056/NEJMp038145
Population-based studies of adverse drug effects.
W. A. Ray (2003)
10.1177/0962280208092347
Use of disease risk scores in pharmacoepidemiologic studies
Patrick G. Arbogast (2009)
10.1097/MJT.0000000000000599
The Impact of Proton Pump Inhibition on Dabigatran Levels in Patients With Atrial Fibrillation
Tomáš Bolek (2019)
10.1053/j.gastro.2016.08.054
Association of Proton Pump Inhibitors With Reduced Risk of Warfarin-Related Serious Upper Gastrointestinal Bleeding.
W. A. Ray (2016)
10.1161/STROKEAHA.117.018395
Real-World Use of Apixaban for Stroke Prevention in Atrial Fibrillation: A Systematic Review and Meta-Analysis
Marco Proietti (2018)
10.1001/jamainternmed.2016.5954
Stroke, Bleeding, and Mortality Risks in Elderly Medicare Beneficiaries Treated With Dabigatran or Rivaroxaban for Nonvalvular Atrial Fibrillation.
David J. Graham (2016)



This paper is referenced by
10.1007/s15004-019-6558-1
Risiko gastrointestinaler Blutungen unter oraler Antikoagulation
H. -C Diener (2019)
10.4081/monaldi.2020.1252
Oral anticoagulant therapy in atrial fibrillation older patients with previous bleeding.
Mario Bo (2020)
10.1007/s40264-019-00866-7
Comparative Effectiveness and Safety of Direct Oral Anticoagulants: Overview of Systematic Reviews
Emanuel Raschi (2019)
10.1007/s10620-020-06408-x
PPIs and Beyond: A Framework for Managing Anticoagulation-Related Gastrointestinal Bleeding in the Era of COVID-19
Parita Patel (2020)
10.1001/jamainternmed.2020.0268
Oral Anticoagulants, Proton Pump Inhibitors, and Fracture.
Chika Edward Uzoigwe (2020)
10.1016/j.ejim.2019.11.017
Proton pump inhibitors and cardiovascular adverse effects: Real or surreal worries?
Antonis A. Manolis (2019)
10.1007/s40265-020-01323-x
Dabigatran Dual Therapy vs Warfarin Triple Therapy Post-Percutaneous Coronary Intervention in Patients with Atrial Fibrillation With/Without a Proton Pump Inhibitor: A Pre-Specified Analysis of the RE-DUAL PCI Trial
José Carlos Nicolau (2020)
10.1002/ccr3.2585
Sustained resolution of anticoagulation related iron deficiency anemia with the use of apixaban
Alex Choo (2020)
10.12968/hmed.2020.0210
A matter of time: duration and choice of venous thromboprophylaxis in patients diagnosed with COVID-19.
Poornima Kumar (2020)
10.1007/s15005-019-0019-0
Risiko gastrointestinaler Blutungen unter oraler Antikoagulation
H. -C Diener (2019)
10.1016/J.BPG.2019.04.003
Changing epidemiology and etiology of upper and lower gastrointestinal bleeding.
Kathryn Oakland (2019)
10.20452/pamw.15136
Bleeding in anticoagulated patients with atrial fibrillation: practical considerations.
Anetta Undas (2020)
VHRM_A_187656 399..408
Ron Pisters (2019)
10.1007/s00108-019-0587-6
Prävention gastrointestinaler Blutungen mittels Protonenpumpenhemmern
Margarete Götz (2019)
10.1182/bloodadvances.2019000572
Systematic review and meta-analysis of the efficacy and safety of apixaban compared to rivaroxaban in acute VTE in the real world.
Madan Raj Aryal (2019)
10.1111/jth.14706
Direct oral anticoagulants: Still too early for prime time after pulmonary endarteriectomy?
Laurent Bertoletti (2020)
10.1007/s00228-019-02692-3
Proton pump inhibitors: why this gap between guidelines and prescribing practices in geriatrics?
Hugues Michelon (2019)
10.1007/s00108-019-0587-6
[Prevention of gastrointestinal bleeding by means of proton pump inhibitors].
Martin Goetz (2019)
10.5009/gnl19009
The Role of Acid Suppressants in the Prevention of Anticoagulant-Related Gastrointestinal Bleeding: A Systematic Review and Meta-Analysis
Chang Seok Bang (2019)
10.3748/wjg.v25.i24.2990
Application of Big Data analysis in gastrointestinal research
Ka-shing Cheung (2019)
10.36290/kar.2020.026
Proton pump inhibitors as part of comedication with antithrombotic drugs: are their indications justified?
Jan Bultas (2020)
10.2147/VHRM.S187656
When to withhold oral anticoagulation in atrial fibrillation – an overview of frequent clinical discussion topics
J. Seelig (2019)
10.1161/CIRCOUTCOMES.119.006058
Rivaroxaban Versus Apixaban for Stroke Prevention in Atrial Fibrillation
Anders Nissen Bonde (2020)
10.1253/circj.cj-19-0426
The Impending Epidemic of Cardiovascular Diseases in Patients With Cancer in Japan.
Yuji Okura (2019)
10.4045/tidsskr.18.0957
Forebygger protonpumpehemmere blødning under antikoagulasjon
Petter Morten Pettersen (2019)
10.1007/s15006-019-0504-x
Darf’s zum DOAK noch ein PPI sein?
H. C. Diener (2019)
10.1055/s-0039-1695735
Proton Pump Inhibitors and Dabigatran Therapy: Impact on Gastric Bleeding and Dabigatran Plasma Levels.
Tomáš Bolek (2019)
10.1007/s00392-019-01526-7
Drug interactions with oral anticoagulants in German nursing home residents: comparison between vitamin K antagonists and non-vitamin K antagonist oral anticoagulants based on two nested case–control studies
Kathrin Jobski (2019)
10.20996/1819-6446-2019-15-4-593-603
Optimization of Pharmacotherapy with Direct Oral Anticoagulants: the Need to Choose the Right Dosage Regimen
Aleksei I. Kochetkov (2019)
10.1111/ijcp.13382
Proton pump inhibitors co-prescribed with warfarin reduce warfarin control as measured by time in therapeutic range.
Victoria Bertram (2019)
10.3802/jgo.2020.31.e10
Comparison of rivaroxaban and dalteparin for the long-term treatment of venous thromboembolism in patients with gynecologic cancers
Jang Ho Lee (2019)
10.1136/bmjqs-2019-009897
Passing the acid test? Evaluating the impact of national education initiatives to reduce proton pump inhibitor use in Australia
Claudia Bruno (2019)
See more
Semantic Scholar Logo Some data provided by SemanticScholar