Severe Stroke Tied to Aspirin Resistance

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http://www.medpagetoday.com/Cardiology/Strokes/36024
Individuals who are resistant to aspirin's antiplatelet effects appear to have more severe ischemic strokes than those who respond to the drug, researchers found.
Among patients admitted with an acute stroke, those shown to be resistant to aspirin with a platelet function assay were significantly more likely to have an NIH Stroke Scale (NIHSS) score of 16 or higher on admission (OR 7.49, 95% CI 1.49 to 48.00), the cutoff for severe stroke, according to Bernard Yan, MD, of Royal Melbourne Hospital in Parkville, Australia, and colleagues.
In addition, resistant patients were more likely to have an Alberta Stroke Program Early CT Score (ASPECTS) of less than 7 (OR 60.0, 95% CI 10.5 to 343.2), indicating a large area of infarction, the researchers reported online in Archives of Neurology.
"Our results support the need for a randomized controlled study to investigate alternative antiplatelet therapy in patients with aspirin resistance," they wrote.
The use of aspirin before a stroke has been associated with less severe symptoms at admission and improved functional outcomes at discharge. And short-term aspirin therapy has been shown to significantly reduce the risks of death and dependency at 6 months following an acute ischemic stroke.
Resistance to aspirin, however, may contribute to poor clinical outcomes in some patients.
Yan and colleagues explored the issue using data from 90 adult patients admitted with an acute ischemic stroke at their center. All had been using aspirin for at least 7 days before stroke onset (median 5 years).
The mean age of the patients was 75, and 64.4% were male.
At admission, the median NIHSS score was 4, indicating minor symptoms. The median ASPECTS was 9, indicating a small area of infarction (the maximum score of 10 indicates a normal CT scan).
As measured by the VerifyNow assay, 28.9% of the patients were resistant to aspirin, defined as an aspirin reaction unit (ARU) of 550 or higher. The median ARU for the entire cohort was 486.
Each 1-point increase in ARU was associated with a 0.03-point increase in NIHSS score (P=0.001) and a 0.02-point decrease in ASPECTS (P less than 0.001). That works out to a 1-point increase in NIHSS score for a 33-point increase in ARU and a 1-point decrease in ASPECTS for a 50-point increase in ARU.
The presence of aspirin resistance was associated with a worse stroke according to both the NIHSS and ASPECTS.
"Platelets are critical to thrombus formation, contributing as much as 50% of the total thrombus volume. Antiplatelet agents decrease platelet aggregation and, in turn, the size and frequency of thrombolytic emboli," the authors wrote.
Thus, they said, "the increased severity and infarct size observed in the present study may be due to larger thrombus formation as a result of inadequate platelet inhibition."
"Aspirin also reduces platelet microaggregates and platelet-derived vasoconstricting products," they added. "This may ease ischemic injury by improving local blood flow. Aspirin-resistant patients may not experience the same therapeutic effect and, as a result, sustain a larger stroke."
Alternatively, other neuroprotective or anti-inflammatory processes could be involved in the observed relationship, Yan and colleagues noted.
They acknowledged that their study was limited by the small sample size, the slight selection bias favoring patients with milder symptoms, and the possible insensitivity of ASPECTS to early ischemic changes.