ArticleClinical pharmacology and therapeutics2021
Association Between Use of Pharmacokinetic-Interacting Drugs and Effectiveness and Safety of Direct Acting Oral Anticoagulants: Nested Case-Control Study.
Article in Clinical pharmacology and therapeutics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 3 of them syntheses that pooled it.
What it found
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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.
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.
Who cites it
57 citing papers in PubMed, 3 syntheses or guidelines pooled it.
- Pooled it
- Effectiveness and safety of concomitant use of direct oral anticoagulants and antiarrhythmic drugs: a systematic review of observational studies.European journal of clinical pharmacology · 2025Pooled it
- Relevant pharmacologic interactions in the concurrent management of brain tumor-related epilepsy and venous thromboembolism: a systematic review.Journal of neuro-oncology · 2022Pooled it
- Effect of Clarithromycin, a Strong CYP3A and P-glycoprotein Inhibitor, on the Pharmacokinetics of Edoxaban in Healthy Volunteers and the Evaluation of the Drug Interaction with Other Oral Factor Xa Inhibitors by a Microdose Cocktail Approach.Cardiovascular drugs and therapy · 2024Trial
- Pharmacokinetics of apixaban and tacrolimus or cyclosporine in kidney and lung transplant recipients.Clinical and translational science · 2022Trial
- Drug-drug interactions of NOACs with comedication: Prevalence and implications for adverse events in patients with atrial fibrillation.Heart rhythm O2 · 2026Article
- An Observational Study of the Effect of Concomitant Levetiracetam on Apixaban Concentrations in a Hospital Cohort.Clinical and translational science · 2026Observational
- Exploring Risks of Adverse Drug Events From Single Drug to Three-Drug Combination.Clinical and translational science · 2026Article
- Venous Thromboembolism and Gut Dysbiosis: Mechanistic Links Between Endotoxemia, Microbial Metabolites, and Thromboinflammation.Nutrients · 2026Review
- When Atrial Fibrillation Meets Alcoholic Liver Cirrhosis: Can Direct Oral Anticoagulants Bridge the Therapeutic Gap?Biomedicines · 2026Review
- Interactions Between Direct Oral Anticoagulants and Drugs Involving CYP-Enzymes and P-gp Transporters Detected by a Clinical Decision Support System: A Retrospective Cohort Study.Cardiovascular drugs and therapy · 2026Article
- Current status of proton pump inhibitor usage in patients with acute coronary syndrome and atrial fibrillation: a cross-sectional study.Frontiers in cardiovascular medicine · 2026Article
- Safety and Effectiveness of Direct Oral Anticoagulants in Combination with Antiseizure Medications: Protocol for a Systematic Review and Meta-analysis.Neurology and therapy · 2025Article
- Odoribacter splanchnicus rescues aging-related intestinal P-glycoprotein damage via GDP-L-fucose secretion.Nature communications · 2025Article
- Profiling Interactions Between Bicyclol and SLC/ABC Transporters: Advancing Clinical Safety and Efficacy in Combination Therapy.Pharmaceutical research · 2025Article
- Article
- Tailoring Anticoagulant Therapy: Managing Interactions Between Carbamazepine and Direct Oral Anticoagulants (DOACs).Cureus · 2025Article
- Drug-Drug Interactions Between Direct Oral Anticoagulants and Other Medications in Patients with Pulmonary Embolism: Results from the Lungenembolie Augsburg (LEA).Clinical pharmacokinetics · 2025Article
- Optimizing care for patients after major anticoagulant-related bleeding: a narrative review and proposal for a clinical care pathway.Research and practice in thrombosis and haemostasis · 2025Review
- Concomitant Drug Interactions With Non-Vitamin K Oral Anticoagulants Are Associated With Bleeding and Mortality Risk in Patients With Nonvalvular Atrial Fibrillation.Journal of the American Heart Association · 2025Article
Corrections and comments
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Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Concomitant use of direct oral anticoagulants (DOACs) and medications with inhibition/induction effect on P-gp/CYP3A might increase risk of bleeding/treatment failure, respectively. We designed a nested case-control study within a Clalit cohort of patients with atrial fibrillation (AF) and a cohort of patients with venous thromboembolism, new users of a DOAC (January 1, 2010 to August 24, 2020). Propensity scores were constructed from demographic/clinical characteristics, and medications at cohort entry. Each case of: (i) serious bleeding event; (ii) stroke/systemic emboli (SE) in patients with AF; (iii) recurrent thromboembolism in patients with thromboembolism, was matched by age, sex, length of follow-up, year of cohort entry, DOAC type, and DOAC indication, to up to 20 controls. Within 89,284 patients with AF and venous thromboembolism and 126,302 patient-years of follow-up, there were 1,587 serious bleeding events. Risk of serious bleeding increased in association with concurrent prescription of P-gp/CYP3A4 inhibitors. Specifically, higher bleeding risk was associated with dabigatran-verapamil, rivaroxaban-verapamil, and rivaroxaban-amiodarone concurrent prescriptions: adjusted odds ratios (ORs) 2.29 (1.13-4.60), 2.18 (1.07-4.40), and 1.68 (1.14-2.49), respectively. There were 1,116 events of stroke/SE, in 79,302 DOAC-treated patients with AF and 118,124 patient-years of follow-up. Concomitant use of phenytoin, carbamazepine, valproic acid, or levetiracetam was associated with risk for stroke/SE: adjusted OR 2.18 (1.55-3.10). Risk of recurrent venous thromboembolism could not be assessed due to the low number of cases. Concurrent prescriptions of dabigatran or rivaroxaban with verapamil, and of rivaroxaban with amiodarone, are associated with increased risk for serious bleeding. Higher risk for stroke/SE in patients with AF is associated with concurrent prescriptions of DOACs with phenytoin, carbamazepine, valproic acid, or levetiracetam.
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