Subdural Hematoma Rates Rise With Higher Antithrombotic Use

Megan Brooks

February 28, 2017

Over roughly the past 15 years, the incidence of subdural hematoma increased in concert with the increased use of antithrombotic drugs, such as low-dose aspirin, vitamin K antagonists (VKAs; warfarin), clopidogrel, and oral anticoagulants, a Danish study indicates.

The increase was most pronounced in patients aged 75 years and older and with use of a VKA.

"The present data add one more piece of evidence to the complex risk-benefit equation of antithrombotic drug use," first author, David Gaist, MD, PhD, Department of Neurology, Odense University Hospital, University of Southern Denmark, told Medscape Medical News.

The study was published online February 28 in JAMA.

Using regional and national data, the study team matched 10,010 patients (mean age, 69.2 years; 34.6% women) with a first-ever subdural hematoma diagnosis from 2000 to 2015 to 400,380 controls from the general population.

Among patients with subdural hematoma, 47.3% were taking antithrombotic medications. The 30-day mortality rate among patients with subdural hematoma was 16.1%.

Current use of low-dose aspirin was associated with a small risk for subdural hematoma; use of clopidogrel and a direct oral anticoagulant (DOAC), with a moderate risk; and use of a VKA, with a higher risk, the researchers found.

Table 1. Subdural Hematoma Rate by Treatment

Treatment Cases (%) Controls (%) Adjusted Odds Ratio (95% Confidence Interval)
Low-dose aspirin 26.7 22.4 1.24 (1.15 - 1.33)
Clopidogrel 5.0 2.2 1.87 (1.57 - 2.24)
DOAC 1.0 0.6 1.73 (1.31 - 2.28)
VKA 14.3 4.9 3.69 (3.38 - 4.03)


The risk for subdural hematoma was highest when a VKA was used concurrently with an antiplatelet drug.

Table 2. Subdural Hematoma Rate With Combined Treatment

Treatment Cases (%) Controls (%) Adjusted Odds Ratio (95% Confidence Interval)
Aspirin + VKA 3.6 1.1 4.00 (3.40 - 4.70)
Clopidogrel + VKA 0.3 0.04 7.93 (4.49 - 14.02)


The researchers also found that the prevalence of antithrombotic drug use increased from 31.0 per 1000 people in the general population in 2000 to 76.9 per 1000 in 2015 (P < .001 for trend). The overall incidence rate of subdural hematoma 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 occurred in those older than age 75 years. The incidence rate in this age group almost doubled in the study period, from 55.1 per 100,000 person-years in 2000 to 99.7 per 100,000 person-years in 2015 (P < .001 for trend).

"The marked increase in the incidence rate of subdural hematoma among those aged 75-plus years was quite surprising," Dr Gaist told Medscape Medical News. "This increase can, at least partly, be explained through increased use of antithrombotic drugs, especially use of a vitamin K antagonist, eg, warfarin."

"Conversely," he noted, "the risk of subdural hematoma associated with low-dose aspirin use was low, and emphasizes that risk of subdural hematoma varied by type of antithrombotic drug. The risk also varied by regimen (ie, monotherapy vs concurrent use of more than one antithrombotic). Concurrent treatment with more than one antithrombotic has been increasingly used in Denmark in recent years, and the majority of such regimens further increased the risk of subdural hematoma."

"It is important to emphasize," Dr Gaist added, "that it is known that antithrombotic drugs result in net benefits overall in patients with clear indications for their use. Having said that, our results do highlight the potential for untoward effects of this group of drugs, particularly warfarin, and warfarin combined with antiplatelet therapy (eg, low-dose aspirin, or clopidogrel)."

"Physicians should therefore be vigilant with regard to prescribing antithrombotic drugs on clear indications and may further wish to make sure that aggressive and complex antithrombotic treatments are not used for longer periods than clearly indicated," Dr Gaist said.

Subdural hematoma is "the neglected intracranial hemorrhage," Robert G. Hart, MD, professor of medicine (neurology), McMaster University/Population Health Research Institute, Hamilton, Ontario, Canada, who wasn't involved in the study, told Medscape Medical News.

"Estimates for relative risk associated with interventions in this 'big data' analysis are inevitably confounded to uncertain degrees by selection bias that cannot be confidently adjusted for using statistical techniques," he noted. Nonetheless, this analysis, coupled with other similar analyses, "gives a relatively consistent picture of the risk of subdural hematoma associated with antithrombotic therapies," Dr Hart commented.

The study had no specific funding. Dr Gaist has received honoraria from AstraZeneca (Sweden) for participation as a coinvestigator on a research project. A complete list of author disclosures is available with the original article.

JAMA. 2017;317:836-846. Abstract

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