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Original Investigation
February 28, 2017

Association of Antithrombotic Drug Use With Subdural Hematoma Risk

Author Affiliations
  • 1Department of Neurology, Odense University Hospital, Odense, Denmark
  • 2Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense
  • 3Centro Español Investigatión Farmacoepidemiológica, Madrid, Spain
  • 4Clinical Pharmacology, Department of Public Health, University of Southern Denmark, Odense
  • 5Department of Neurosurgery, Odense University Hospital, Odense, Denmark
JAMA. 2017;317(8):836-846. doi:10.1001/jama.2017.0639
Key Points

Question  Are changes in subdural hematoma incidence related to antithrombotic drug use?

Findings  In this observational study with 10 010 subdural hematoma cases and 400 380 controls, subdural hematoma risk was significantly associated with antithrombotic drug use, in particular use of a vitamin K antagonist (adjusted odds ratio, 3.69). An observed increase in antithrombotic drug use was related to an increase in subdural hematoma incidence from 10.9 per 100 000 person-years in 2000 to 19.0 per 100 000 person-years in 2015.

Meaning  The increased incidence of subdural hematoma was associated with increased use of antithrombotic drugs, especially use of a vitamin K antagonist.

Abstract

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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