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Published on: February 26, 2013
Proton Pump Inhibitor Use and Clinical Outcomes in Atrial Fibrillation During Anticoagulation
Do-Young Kim1, Hye Young Lee2, Eileen Laurel Yoon3
1Department of Cardiology, Ajou University School of Medicine, World Cup-ro 164, Yeongtong-gu, Suwon 16499, Republic of Korea.
Insights
Proton pump inhibitor use in atrial fibrillation patients on anticoagulants increases risks for bleeding and mortality, but not blood clots. Further research is needed to understand these associations.
Area of Science:
- Cardiology
- Pharmacology
- Clinical Research
Background:
- Proton pump inhibitors (PPIs) are frequently prescribed with oral anticoagulants (OACs) for atrial fibrillation (AF) patients.
- Evidence on PPIs' impact on non-gastrointestinal bleeding and thromboembolic events in AF patients is limited.
Purpose of the Study:
- To investigate the association between concomitant PPI use and thromboembolic events, bleeding outcomes, and all-cause mortality in AF patients on OACs.
- To evaluate risks beyond upper gastrointestinal bleeding associated with PPI use in this population.
Main Methods:
- Retrospective multicenter cohort study of 11,203 AF patients initiating OAC therapy.
- Time-varying PPI exposure modeled with a 7-day lag.
- Time-dependent Cox proportional hazard models used to estimate associations.
Main Results:
- PPI use was linked to increased risk of a composite outcome (HR 1.29), major bleeding (HR 1.80), gastrointestinal bleeding (HR 1.77), and all-cause mortality (HR 1.58).
- No significant association found between PPI use and thromboembolic events.
- Robustness analyses generally supported the observed associations, with variations based on exposure timing.
Conclusions:
- Concomitant PPI use in AF patients on OACs is associated with elevated risks of bleeding and all-cause mortality.
- The study did not find an association between PPI use and thromboembolic events.
- Findings highlight potential risks of PPIs beyond GI protection in anticoagulated AF patients, emphasizing observational nature of associations.
Abstract:
Purpose: Proton pump inhibitors are commonly used during oral anticoagulant therapy in patients with atrial fibrillation, but evidence regarding outcomes beyond upper gastrointestinal bleeding remains limited. We evaluated whether concomitant proton pump inhibitor use during oral anticoagulant therapy was associated with thromboembolic events, bleeding outcomes, and all-cause mortality. Methods: This retrospective multicenter cohort study included patients with atrial fibrillation who initiated oral anticoagulant therapy. Concomitant proton pump inhibitor use was modeled as a time-varying exposure with a prespecified 7-day lag. The primary outcome was a composite of thromboembolic events, major bleeding, and all-cause mortality. Secondary outcomes included each component outcome and gastrointestinal bleeding. Associations were estimated using time-dependent Cox proportional hazard models after multiple imputation of missing baseline variables. Results: Among 11,203 patients (median age 71 years [interquartile range 62-78]; 4743 women [42.3%]), 7-day lagged time-varying proton pump inhibitor exposure was associated with a higher risk of the composite outcome (hazard ratio 1.29, 95% confidence interval 1.08-1.55), major bleeding (1.80, 1.36-2.37), gastrointestinal bleeding (1.77, 1.18-2.66), and all-cause mortality (1.58, 1.00-2.48). No statistically significant association was observed for thromboembolic events. Across robustness analyses, the overall pattern was broadly maintained, although estimates varied according to exposure timing. Conclusions: In this observational cohort of patients with atrial fibrillation receiving oral anticoagulant therapy, concomitant proton pump inhibitor use modeled with a 7-day lagged time-varying framework was associated with higher risks of several bleeding-related outcomes and all-cause mortality, but not thromboembolism. These findings should be interpreted as associations rather than causal effects.
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