The DOI matches its Crossref record; 35 of the 35 references it cites were found in a registry or an index.
Use of single and combined antithrombotic therapy and risk of serious upper gastrointestinal bleeding: population based case-control study
Open accessAbstract
OBJECTIVES: To assess the risk of serious upper gastrointestinal bleeding associated with the newer antithrombotic agents used alone or in combination with other antithrombotic drugs; to describe the trends in use of antithrombotic drugs in the background population. DESIGN: Population based case-control study. SETTING: Funen County, Denmark (population 470,000). SUBJECTS: 1443 cases of serious upper gastrointestinal bleeding identified during 2000-4; 57,720 age and sex matched controls. MAIN OUTCOME MEASURE: Exposure to low dose aspirin, clopidogrel, dipyridamole, vitamin K antagonists, and combined antithrombotic treatment. RESULTS: Adjusted odds ratios associating drug use with upper gastrointestinal bleeding were 1.8 (95% confidence interval 1.5 to 2.1) for low dose aspirin, 1.1 (0.6 to 2.1) for clopidogrel, 1.9 (1.3 to 2.8) for dipyridamole, and 1.8 (1.3 to 2.4) for vitamin K antagonists. Corresponding figures for combined use were 7.4 (3.5 to 15) for clopidogrel and aspirin, 5.3 (2.9 to 9.5) for vitamin K antagonists and aspirin, and 2.3 (1.7 to 3.3) for dipyridamole and aspirin. Other combinations were used too infrequently to allow estimation. The number of treatment years needed to produce one excess case varied from 124 for the clopidogrel-aspirin combination to 8800 for clopidogrel alone. During the study period, exposure to combined antithrombotic regimens increased by 425% in the background population. CONCLUSION: Antithrombotic treatment is becoming increasingly aggressive. Combined antithrombotic treatment confers particular risk and is associated with high incidence of gastrointestinal bleeding.
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“Thus, gastrointestinal mucosal bleeding appears to be due to pre-existing mucosal lesions associated with defective primary haemostasis secondary to platelet inhibition, rather than with a specific antiplatelet drug.”
From 2023 ESC guidelines for the management of cardiovascular disease in patients with diabetes. (2023) · cites this paper as [338]
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“Combined antithrombotic drugs, while effective, increase major bleeding risk.337,338”
From 2023 ESC guidelines for the management of cardiovascular disease in patients with diabetes. (2023) · cites this paper as [338]
In the citing paper
“Large observational studies or head-to-head RCTs show similar rates of gastrointestinal and non-gastrointestinal major bleeding for single antiplatelet therapy (SAPT) with low-dose ASA or a P2Y 12 inhibitor (clopidogrel or ticagrelor).”
From 2023 ESC guidelines for the management of cardiovascular disease in patients with diabetes. (2023) · cites this paper as [338]
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Clopidogrel and Aspirin versus Aspirin Alone for the Prevention of Atherothrombotic Events
Bhatt, D. L., Fox, K. A. A., Hacke, W., Berger, P. B., Black, H. R., Boden, W. E., Cacoub, P., Cohen, E. A., Creager, M. A., Easton, J. D., et al. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa060989 · Cited by 2,819
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Expert consensus on medication therapy for acid-related diseases
Hu, Y. (2026) · Precision medication. · doi:10.1016/j.prmedi.2026.100081
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BÖLÜKBAŞI, S., & Dere, B. (2026) · Arşiv Kaynak Tarama Dergisi · doi:10.17827/aktd.1788275
Zhou, X., Zhou, Z., Teng, J., Fan, X., 张春华, Wang, S., Su, X., & Liu, Z. (2026) · Journal of Stroke and Cerebrovascular Diseases · doi:10.1016/j.jstrokecerebrovasdis.2026.108762
Gómez-Lumbreras, A., Tawfik, A. G., Reese, T. S., Witt, D. M., Fiol, G. D., & Malone, D. C. (2026) · Pharmacotherapy The Journal of Human Pharmacology and Drug Therapy · doi:10.1002/phar.70205
Deptuła‐Krawczyk, E., Wojtuń, S., Hałas, K., Gielerak, G. G., & Kowal, J. (2010) · DOAJ (DOAJ: Directory of Open Access Journals)
Metadata
- Authors
- Hallas, J., Dall, M., Andries, A., Andersen, B. S., Aalykke, C., Hansen, J. M., Andersen, M., & Lassen, A. T.
- Affiliations
- University of Southern Denmark (DK)
- Odense University Hospital (DK)
- Corresponding author
- Hallas, Jesper
- Venue
- BMJ
- Publisher
- BMJ
- Published
- 2006-09-19
- Volume
- 333
- Issue
- 7571
- Pages
- 726
- ISSN
- 0007-1447 (ISSN-L)
- 0959-8138
- 1468-5833
- OpenAlex
- W2120642548
- Cited by
- 403
- References
- 35
- Citations by year
- 2026: 6 · 2025: 4 · 2024: 12 · 2023: 17 · 2022: 9 · 2021: 11 · 2020: 16 · 2019: 14 · 2018: 10 · 2017: 23 · 2016: 25 · 2015: 25 · 2014: 33 · 2013: 26 · 2012: 25
- FWCI
- 17.99
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- BMJ (publishedVersion)
- PubMed (publishedVersion)
- University of Southern Denmark Research Portal (University of Southern Denmark) (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Antiplatelet Therapy and Cardiovascular Diseases
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal Bleeding Diagnosis and Treatment
- Health Sciences › Medicine › Gastroenterology › Helicobacter pylori-related gastroenterology studies
- Keywords
- upper gastrointestinal bleeding, antithrombotic therapy, clopidogrel, aspirin, dipyridamole, vitamin K antagonists, combination antithrombotic therapy, bleeding risk
- MeSH terms
- Aged, Aspirin, Drug Therapy, Combination, Female, Fibrinolytic Agents, Gastrointestinal Hemorrhage, Humans, Male, Peptic Ulcer Hemorrhage, Platelet Aggregation Inhibitors, Stomach Ulcer, Case-Control Studies
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