Association of antithrombotic drug use with subdural hematoma risk
Open accessAbstract
IMPORTANCE: Incidence of subdural hematoma has been reported to be increasing. To what extent this is related to increasing use of antithrombotic drugs is unknown. OBJECTIVES: To estimate the association between use of antithrombotic drugs and subdural hematoma risk and determine trends in subdural hematoma incidence and antithrombotic drug use in the general population. DESIGN, SETTING, AND PARTICIPANTS: Case-control study of 10 010 patients aged 20 to 89 years with a first-ever subdural hematoma principal discharge diagnosis from 2000 to 2015 matched by age, sex, and calendar year to 400 380 individuals from the general population (controls). Subdural hematoma incidence and antithrombotic drug use was identified using population-based regional data (population: 484 346) and national data (population: 5.2 million) from Denmark. Conditional logistic regression models were used to estimate odds ratios (ORs) that were adjusted for comorbidity, education level, and income level. EXPOSURES: Use of low-dose aspirin, clopidogrel, a vitamin K antagonist (VKA), a direct oral anticoagulant, and combined antithrombotic drug treatment. MAIN OUTCOMES AND MEASURES: Association of subdural hematoma with antithrombotic drug use, subdural hematoma incidence rate, and annual prevalence of treatment with antithrombotic drugs. RESULTS: Among 10 010 patients with subdural hematoma (mean age, 69.2 years; 3462 women [34.6%]), 47.3% were taking antithrombotic medications. Current use of low-dose aspirin (cases: 26.7%, controls: 22.4%; adjusted OR, 1.24 [95% CI, 1.15-1.33]), clopidogrel (cases: 5.0%, controls: 2.2%; adjusted OR, 1.87 [95% CI, 1.57-2.24]), a direct oral anticoagulant (cases: 1.0%, controls: 0.6%; adjusted OR, 1.73 [95% CI, 1.31-2.28]), and a VKA (cases: 14.3%, controls: 4.9%; adjusted OR, 3.69 [95% CI, 3.38-4.03]) were associated with higher risk of subdural hematoma. The risk of subdural hematoma was highest when a VKA was used concurrently with an antiplatelet drug (low-dose aspirin and a VKA: 3.6% of cases and 1.1% of controls; adjusted OR, 4.00 [95% CI, 3.40-4.70]; clopidogrel and a VKA: 0.3% of cases and 0.04% of controls; adjusted OR, 7.93 [95% CI, 4.49-14.02]). The prevalence of antithrombotic drug use increased from 31.0 per 1000 individuals from the general population in 2000 to 76.9 per 1000 individuals in 2015 (P < .001 for trend). The overall subdural hematoma incidence rate increased from 10.9 per 100 000 person-years in 2000 to 19.0 per 100 000 person-years in 2015 (P < .001 for trend). The largest increase was among older patients (>75 years; n = 4441) who experienced an increase from 55.1 per 100 000 person-years to 99.7 per 100 000 person-years (P < .001 for trend). CONCLUSIONS AND RELEVANCE: In Denmark, antithrombotic drug use was associated with higher risk of subdural hematoma; and the highest odds of subdural hematoma was associated with combined use of a VKA and an antiplatelet drug. The increased incidence of subdural hematoma from 2000 to 2015 appears to be associated with the increased use of antithrombotic drugs, particularly use of a VKA among older patients.
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A meta-analysis showed that gastroprotectant drugs significantly reduce the risk of gastrointestinal bleeding in patients on single or combined antithrombotic drugs.
“A meta-analysis showed that gastroprotectant drugs significantly reduce the risk of gastrointestinal bleeding in patients on single or combined antithrombotic drugs.351”
From 2023 ESC guidelines for the management of cardiovascular disease in patients with diabetes. (2023) · cites this paper as [351]
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From 2023 ESC guidelines for the management of cardiovascular disease in patients with diabetes. (2023) · cites this paper as [351]
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Cites
Ruff, C. T., Giugliano, R. P., Braunwald, E., Hoffman, E. B., Deenadayalu, N., Ezekowitz, M. D., Camm, A. J., Weitz, J. I., Lewis, B. S., Parkhomenko, A., et al. (2014) · The Lancet · doi:10.1016/s0140-6736(13)62343-0 · Cited by 5,051 · see citing works
Hart, R. G., Pearce, L. A., & Aguilar, M. I. (2007) · Annals of Internal Medicine · doi:10.7326/0003-4819-146-12-200706190-00007 · Cited by 4,793 · see citing works
The Danish Civil Registration System
Pedersen, C. (2011) · Scandinavian Journal of Public Health · doi:10.1177/1403494810387965 · Cited by 4,713 · see citing works
The Danish National Patient Register
Lynge, E., Sandegaard, J. L., & Rebolj, M. (2011) · Scandinavian Journal of Public Health · doi:10.1177/1403494811401482 · Cited by 3,968 · see citing works
Jensen, V. M., & Rasmussen, A. W. (2011) · Scandinavian Journal of Public Health · doi:10.1177/1403494810394715 · Cited by 1,472 · see citing works
ANTICOAGULANT DRUGS IN THE TREATMENT OF PULMONARY EMBOLISM
Barritt, D. W., & Jordan, S. C. (1960) · The Lancet · doi:10.1016/s0140-6736(60)92299-6 · Cited by 1,362 · see citing works
Thygesen, L. C., Daasnes, C., Thaulow, I., & Brønnum‐Hansen, H. (2011) · Scandinavian Journal of Public Health · doi:10.1177/1403494811399956 · Cited by 1,089 · see citing works
Risk Factors for Intracranial Hemorrhage in Outpatients Taking Warfarin
Hylek, E. M., & Singer, D. E. (1994) · Annals of Internal Medicine · doi:10.7326/0003-4819-120-11-199406010-00001 · Cited by 921 · see citing works
The Danish prescription registries.
Gaist, D., Sørensen, H. T., & Hallas, J. (1997) · PubMed · Cited by 570 · see citing works
Self-citationDeath and Disability from Warfarin-Associated Intracranial and Extracranial Hemorrhages
Fang, M. C., Go, A. S., Chang, Y., Hylek, E. M., Henault, L. E., Jensvold, N. G., & Singer, D. E. (2007) · The American Journal of Medicine · doi:10.1016/j.amjmed.2006.07.034 · Cited by 510 · see citing works
Balser, D. Y., Farooq, S., Mehmood, T., et al. (2015) · Journal of neurosurgery · doi:10.3171/2014.9.jns141550 · Cited by 440 · see citing works
Larsen, T. B., Skjøth, F., Nielsen, P. B., Kjældgaard, J. N., & Lip, G. Y. H. (2016) · BMJ · doi:10.1136/bmj.i3189 · Cited by 440 · see citing works
Hart, R. G., Diener, H., Yang, S., Connolly, S. J., Wallentin, L. C., Reilly, P. A., Ezekowitz, M. D., & Yusuf, S. (2012) · Stroke · doi:10.1161/strokeaha.112.650614 · Cited by 405 · see citing works
Hallas, J., Dall, M., Andries, A., Andersen, B. S., Aalykke, C., Hansen, J. M., Andersen, M., & Lassen, A. T. (2006) · BMJ · doi:10.1136/bmj.38947.697558.ae · Cited by 403 · see citing works
Self-citationChronic subdural haematoma in the elderly
Adhiyaman, V., Asghar, M., Ganeshram, K. N., & Bhowmick, B. K. (2002) · Postgraduate Medical Journal · doi:10.1136/pmj.78.916.71 · Cited by 332 · see citing works
Baechli, H., Nordmann, A. J., Bucher, H. C., et al. (2004) · Neurosurgical Review · doi:10.1007/s10143-004-0337-6 · Cited by 279 · see citing works
Chronic subdural haematomas and anticoagulation or anti-thrombotic therapy
Rust, T. M., Kiemer, N., & Erasmus, A. (2006) · Journal of Clinical Neuroscience · doi:10.1016/j.jocn.2004.12.013 · Cited by 209 · see citing works
Lindvall, P., & Koskinen, L. (2009) · Journal of Clinical Neuroscience · doi:10.1016/j.jocn.2009.01.001 · Cited by 151 · see citing works
Antiplatelet/Anticoagulant Agents and Chronic Subdural Hematoma in the Elderly
BONIS, P. D., Trevisi, G., de Waure, C., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0068732 · Cited by 116 · see citing works
Anticoagulant drugs in treatment of pul-monary embolism: A controlled trial.
Barritt, D. W. (1960) · The Lancet · Cited by 84 · see citing works
Aspirin as a risk factor for hemorrhage in patients with head injuries
Reymond, M. A., Marbet, G. A., Radii, E. W., et al. (1992) · Neurosurgical Review · doi:10.1007/bf02352062 · Cited by 70 · see citing works
Adelborg, K., Grove, E. L., Sundbøll, J., Laursen, M., & Schmidt, M. (2016) · Heart · doi:10.1136/heartjnl-2016-309402 · Cited by 52 · see citing works
Vitamin K Antagonists and Risk of Subdural Hematoma
Connolly, B. J., Pearce, L. A., & Hart, R. G. (2014) · Stroke · doi:10.1161/strokeaha.114.005430 · Cited by 39 · see citing works
Aspirin Therapy and Risk of Subdural Hematoma: Meta-analysis of Randomized Clinical Trials
Connolly, B. J., Pearce, L. A., Kurth, T., Kase, C. S., & Hart, R. G. (2013) · Journal of Stroke and Cerebrovascular Diseases · doi:10.1016/j.jstrokecerebrovasdis.2013.01.007 · Cited by 36 · see citing works
Poulsen, F. R., Halle, B., Pottegård, A., et al. (2016) · Pharmacoepidemiology and Drug Safety · doi:10.1002/pds.4058 · Cited by 36 · see citing works
Self-citationA National Survey of Traumatic Brain Injuries Admitted to Hospitals in Sweden from 1987 to 2010
Pedersen, K., Fahlstedt, M., Jacobsson, A., Kleiven, S., & von Holst, H. (2015) · Neuroepidemiology · doi:10.1159/000381780 · Cited by 29 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- Rothman K, Greenland S, Lash T. Modern Epidemiology. 3rd ed. Philadelphia, PA: Wolters Kluwer Health, Lippincott Williams & Wilkins; 2008.
Cited by
Sorted by citations
2023 ESC guidelines for the management of cardiovascular disease in patients with diabetes.
Marx, N., Federici, M., Schütt, K., Müller-Wieland, D., Ajjan, R. A., Antunes, M. J., Christodorescu, R. M., Crawford, C., Di Angelantonio, E., Eliasson, B., et al. (2023) · European Heart Journal · doi:10.1093/eurheartj/ehad192 · Cited by 1,642 · see citing works
- Authors
- Gaist, D., García Rodríguez, L. A., Hellfritzsch, M., Poulsen, F. R., Halle, B., Hallas, J., & Pottegård, A.
- Affiliations
- University of Southern Denmark (DK)
- Centro Español Investigatión Farmacoepidemiológica, Madrid, Spain
- Odense University Hospital (DK)
- Corresponding author
- Gaist, David
- Venue
- JAMA
- Publisher
- American Medical Association (AMA)
- Published
- 2017-02-28
- Volume
- 317
- Issue
- 8
- Pages
- 836
- ISSN
- 0002-9955 (ISSN-L)
- 0098-7484
- OpenAlex
- W2594331891
- Cited by
- 203
- References
- 27
- Citations by year
- 2026: 29 · 2025: 30 · 2024: 23 · 2023: 21 · 2022: 23 · 2021: 17 · 2020: 18 · 2019: 14 · 2018: 13 · 2017: 14 · 2016: 1
- FWCI
- 11.23
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- JAMA (publishedVersion)
- PubMed (publishedVersion)
- University of Southern Denmark Research Portal (University of Southern Denmark) (publishedVersion, other-oa)
- Funders
- Bristol-Myers Squibb
- Pfizer
- AstraZeneca
- Topics
- Health Sciences › Medicine › Neurology › Neurosurgical Procedures and Complications
- Health Sciences › Medicine › Surgery › Spinal Hematomas and Complications
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Antiplatelet Therapy and Cardiovascular Diseases
- Keywords
- subdural hematoma, antithrombotic agents, low-dose aspirin, clopidogrel, vitamin K antagonists, direct oral anticoagulants, anticoagulant-induced bleeding, drug safety, risk factors, Denmark, population-based registry, case-control study, drug use trends
- MeSH terms
- Clopidogrel, Adult, Aged, Aged, 80 and over, Anticoagulants, Aspirin, Denmark, Drug Therapy, Combination, Female, Fibrinolytic Agents, Hematoma, Subdural, Humans, Male, Middle Aged, Platelet Aggregation Inhibitors, Risk Factors, Ticlopidine, Vitamin K, Comorbidity, Incidence, Odds Ratio, Case-Control Studies, Young Adult
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