Antithrombotic Drugs and Risk of Subdural Hematoma

Study Questions:

What is the association between use of antithrombotic drugs and subdural hematoma risk?


This was a case-control study of 10,010 patients aged 20-89 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. Use of low-dose aspirin, clopidogrel, a vitamin K antagonist (VKA), a direct oral anticoagulant, and combined antithrombotic drug treatment were assessed. The main outcome measure was the association of subdural hematoma with antithrombotic drug use, subdural hematoma incidence rate, and annual prevalence of treatment with antithrombotic drugs. Conditional logistic regression models were used to estimate odds ratios (ORs) that were adjusted for comorbidity, education level, and income level.


Among 10,010 patients with subdural hematoma (mean age, 69.2 years; 3,462 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 1,000 individuals from the general population in 2000 to 76.9 per 1,000 individuals in 2015 (p < 0.001 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 < 0.001 for trend). The largest increase was among older patients (>75 years; n = 4,441) who experienced an increase from 55.1 per 100,000 person-years to 99.7 per 100,000 person-years (p < 0.001 for trend).


The authors concluded that antithrombotic drug use was associated with higher risk of subdural hematoma, and the highest odds of subdural hematoma were associated with combined use of a VKA and an antiplatelet drug.


This study reports that 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. Furthermore, concomitant use of >1 antithrombotic drug was related to substantially higher subdural hematoma risk, which was particularly marked for combined treatment of clopidogrel with a VKA. Overall, these results are compatible with antithrombotic drugs playing a greater role in predisposed patients (e.g., due to age-related brain atrophy) with a history of mild to moderate head trauma compared with patients experiencing a severe head trauma for whom there is a minimal role for additional risk factors. This finding has significant public health implications because the risk of experiencing a small to moderate head trauma exceeds the probability of experiencing a severe head injury.

Clinical Topics: Anticoagulation Management, Geriatric Cardiology, Prevention, Vascular Medicine

Keywords: Anticoagulants, Aspirin, Atrophy, Geriatrics, Hematoma, Subdural, Outcome Assessment (Health Care), Platelet Aggregation Inhibitors, Primary Prevention, Risk Factors, Ticlopidine, Vitamin K

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