Subdural hematoma risk is significantly associated with antithrombotic drug use, particularly the combined use of a vitamin K antagonist (VKA) and antiplatelet drug, according to a study published in JAMA.

David Gaist, MD, PhD, from the Odense University Hospital at the University of Southern Denmark, Odense, and colleagues conducted a case-control study of 10,010 patients aged 20 to 89 years with a first-time diagnosis of subdural hematoma from 2000 to 2015. Participants were matched by age, sex, and calendar year to 400,380 control participants. Subdural hematoma incidence and antithrombotic drug use was identified using population-based regional data (484,346) and national data (5.2 million) from Denmark.

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Participants were exposed to the use of low-dose aspirin, clopidogrel, VKA, a direct oral anticoagulant, and a combined antithrombotic drug treatment. The primary outcome was defined as association of subdural hematoma with antithrombotic drug use, subdural hematoma incidence rate, and annual prevalence of treatment with antithrombotic drugs.

Among 10,010 patients with subdural hematoma, 3462 were women (34.6%) with a mean age of 69.2 years. A total of 47.3% were taking antithrombotic medications. Use of low-dose aspirin (cases, 26.7%; controls, 22.4%), clopidogrel (cases, 5.0%; controls, 2.2%), a direct oral anticoagulant (cases, 1.0%; controls 0.6%), and a VKA (cases, 14.3%; controls 4.9%) were associated with a higher risk of subdural hematoma. The risk of subdural hematoma was highest when a VKA was combined with an antiplatelet drug (low-dose aspirin and a VKA: 3.6% of cases and 1.1% of controls; adjusted odds ratio, 4.0; clopidogrel and a VKA: 0.3% of cases and 0.04% of controls; adjusted odds ratio, 7.93).

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. 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. The largest increase was among older patients (>75 years) who experienced an increase from 55.1 per 100,000 person-years to 99.7 per 100,000 person-years.

“In this case-control study that included 10,010 patients with subdural hematoma, low-dose aspirin was associated with a small risk, use of clopidogrel and a direct oral anticoagulant with a moderate risk, and use of a VKA with a higher risk of subdural hematoma,” the authors stated.


  1. Gaist D, García Rodríguez LA, Hellfritzsch M, et al. Association of antithrombotic drug use with subdural hematoma risk. JAMA. 28 February 2017. doi: 10.1001/jama.2017.0639