Association of Direct Oral Anticoagulant-Proton Pump Inhibitor Co-Therapy with Adverse Outcomes: A Population-Based Cohort Study
Bibliographic record
Abstract
BACKGROUND: Direct-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. OBJECTIVE: To determine the risk of clinically important thromboembolic and bleeding events and death in patients concomitantly prescribed DOACs and PPIs compared with DOAC alone. METHODS: We 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. RESULTS: We 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.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".