Evidence map›Paper›PMID 40437847›Full record

ArticleThe Annals of pharmacotherapy2026

Association of Direct Oral Anticoagulant-Proton Pump Inhibitor Co-Therapy with Adverse Outcomes: A Population-Based Cohort Study.

Mei Wang, J Michael Paterson, Francis Nguyen, Deborah M Siegal, Laura Targownik, Anne M Holbrook

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In one paragraph

Article in The Annals of pharmacotherapy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Trial
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Mei WangDepartment of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada.ORCID 0000-0001-5974-1450
J Michael PatersonICES, Toronto, ON, Canada.
Francis NguyenICES, Toronto, ON, Canada.
Deborah M SiegalDivision of Hematology, Department of Medicine, University of Ottawa, Ottawa, ON, Canada.
Laura TargownikDivision of Gastroenterology and Hepatology, Departmental of Medicine, University of Toronto, Toronto, ON, Canada.
Anne M HolbrookDepartment of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada.ORCID 0000-0002-3371-4187

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundDirect-acting oral anticoagulants (DOACs) are first-line therapy for atrial fibrillation and for venous thromboembolism prevention and treatment. In addition, proton pump inhibitors (PPIs) are recommended by the ACC Expert Consensus for patients receiving DOAC.

objectiveTo determine the risk of clinically important thromboembolic and bleeding events and death in patients concomitantly prescribed DOACs and PPIs compared with DOAC alone.

methodsWe undertook a population-based cohort study of Ontario residents aged 66 years or older who were newly dispensed a DOAC from 2009 to 2020. The primary outcome was a composite of clinically relevant bleeding, thrombotic events, and all-cause death. We then used a time-dependent Cox regression model to estimate the adjusted hazard of outcomes during time periods where patients were exposed vs not exposed to PPI.

resultsWe included 283 771 new DOAC users (mean age 78.3 years, 49.4% female). The age/sex-standardized outcome event rate of the composite outcome was higher in the DOAC-PPI cohort [20.2 (95% CI 20.0-20.5) per 100 person-years] than in the DOAC-alone cohort [15.2 (95% CI 15.1-15.4) per 100 person-years]. In time-dependent Cox regression analyses examining time periods during DOAC-PPI co-therapy vs DOAC alone, risks were elevated for all outcomes during periods of PPI co-therapy, suggesting residual confounding. In a secondary analysis of patients receiving DOAC-PPI co-therapy (n = 115 493), periods of DOAC-PPI co-therapy were associated with a greater hazard for death (HR 2.24, 95% CI 2.14-2.35), but a lower risk for both thrombosis (HR 0.93, 95% CI 0.89-0.96) and clinically relevant bleeding (HR 0.79, 95% CI 0.76-0.81). CONCLUSION AND RELEVANCE: Our cohort study of older adults suggests that DOAC-PPI co-therapy is associated with decreased upper GI bleeding but increased mortality. Since the implications are major and may be due to residual confounding, we recommend that the findings be verified in randomized trials before clinical application.

Indexed as

AnticoagulantsFactor Xa InhibitorsProton Pump InhibitorsAdministration, OralAgedAged, 80 and overAtrial FibrillationCohort StudiesDrug Therapy, CombinationFemaleHemorrhageHumansMaleOntarioProportional Hazards ModelsVenous ThromboembolismAnticoagulantsFactor Xa InhibitorsProton Pump Inhibitorsbleeding disorders and coagulopathiescardiologydirect oral anticoagulantsgastroenterologypopulation-based studyproton pump inhibitorsvascular medicine

Identifiers

PMID40437847
PMCPMC12743720

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.