MedWire News: Vitamin K antagonists (VKAs) may increase risk for subarachnoid hemorrhage (SAH) in the general population, whereas platelet aggregation inhibitors (PAIs) do not, say researchers.
Roelof Risselada (Erasmus MC, Rotterdam, The Netherlands) and colleagues note that although both classes of drugs have previously been associated with an increased risk for intracranial hemorrhage (ICH), the specific risk for SAH was unclear, especially since confounding by indication may affect results.
To address the issue of residual confounding, the researchers used three study designs to examine the association between antithrombotic drug use and the risk for SAH.
The first design was a population-based case-control study, and the second design was a case cross-over study, which accounted for measured and unmeasured confounders by using each case as its own control based on past experience. The final study design - a case-time-control study - accounted for time-trends in exposure to the drugs that may act as confounder in the case-crossover design.
The study population was comprised of 1004 patients with SAH and 10,033 matched controls who were registered in a Dutch national drug-dispensing database.
In the case-control analysis, use of PAIs was associated with a significantly increased risk for SAH (odds ratio [OR]=1.32) compared with no-use, whereas use of VKAs was associated with a non-significant increased risk (OR=1.29).
Accounting for confounding by indication in the case-crossover analysis, attenuated the association between SAH and PAIs (OR=1.04) but strengthened the association between SAH and VKAs to a statistically significant level (OR=2.46).
Finally, the case-time-control analysis confirmed the lack of association between PAIs and SAH with an OR of 0.5, and slightly attenuated the association between SAH and VKAs (OR=1.98).
Risselada and co-authors say that their findings indicate an association between VKAs and SAH that cannot be explained by unmeasured confounding.
"Our results are of clinical relevance for the growing patient group with a recent transient ischemic attack or minor stroke in whom a work-up for carotid or intracranial stenosis reveals an intracranial aneurysm," they remark in the Journal of Thrombosis and Haemostasis.
They add that the findings suggest that "PAIs can be prescribed safely to these patients."
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