according to data published online Feb. 28 in JAMA.
A retrospective case-control study of 10,010 patients aged 20-89 years with a first-time subdural hematoma, matched by age, sex, and year to 400,380 general controls, showed treatment with a vitamin K antagonist was associated with a 3.69 greater risk of subdural hematoma, compared with controls, and a fourfold increase in risk when used concurrently with an antiplatelet drug (JAMA. 2017;317:836-46.).
Low-dose aspirin alone was associated with a 24% increase in the risk of subdural hematoma; clopidogrel was associated with an 87% increase; and a direct oral anticoagulant such as dabigatran etexilate, rivaroxaban, or apixaban was associated with a 73% increase in risk.
Antithrombotic drugs were also associated with an increased risk of death from a subdural hematoma within 30 days after discharge for the hematoma’s diagnosis, an effect most evident with a direct oral anticoagulant or vitamin K antagonist.
Over the course of the Danish population-based study, which covered 2000-2015, the prevalence of antithrombotic drug use more than doubled, from 31 individuals per 1,000 to 76.9 per 1,000.
At the same time, the incidence of subdural hematoma nearly doubled (10.9 per 100,000 person-years to 19 per 100,000 person-years). The increase in subdural hematoma was greatest among older patients, from 55.1 per 100,000 person-years to 99.7 per 100,000 person-years.
“Although use of antithrombotic drugs has long been recognized as a risk factor for subdural hematoma, previous studies were either based exclusively on patients with subdural hematoma (i.e.,with no comparison group) or focused exclusively on patients treated with an anticoagulant,” wrote David Gaist, MD, PhD, of Odense University Hospital in Denmark and coauthors.
While the risk of subdural hematoma was greatest for the shortest duration of treatment with low-dose aspirin, the risk remained steady across all durations of treatment with clopidogrel and did not vary significantly for direct oral anticoagulants or vitamin K antagonists.
Women were more likely to show an increased risk of subdural hematoma with low-dose aspirin or vitamin K antagonist than men.
The analysis also showed that the association between low-dose aspirin and subdural hematoma was significantly higher for individuals aged 75-89 years than for those aged 20-64 years.
“Furthermore, the present results emphasize that the major shifts in patterns of antithrombotic drug treatment for older individuals, and the increasing use of more aggressive antithrombotic regimens, have already had a major effect on subdural hematoma incidence,” the authors wrote.
Four authors declared funds from the pharmaceutical industry, including one advisory board position. No other conflicts of interest were declared.