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Aspirin resistance tied to size, severity of ischemic stroke
  November 21, 2012 Megan Brooks

Chicago, IL - Aspirin resistance is common in patients with acute ischemic stroke and is associated with more severe stroke and larger infarct size, according to a study published November 19, 2012 in the Archives of Neurology [1].

"Our results support the need for a randomized controlled study to investigate alternative antiplatelet therapy in patients with aspirin resistance," Dr Bernard Yan (Melbourne Hospital, Parkville, Victoria, Australia) and colleagues conclude.

A novel finding

Aspirin is widely used in the treatment of ischemic stroke, reducing both its risk of recurrence and severity. Aspirin resistance is defined as the inability to decrease thromboxane A2 levels with aspirin therapy, they note, and has been linked to increased risk of recurrent stroke and poor outcomes.

In the current study, Yan et al tested for aspirin resistance among 90 patients with acute ischemic stroke who had been on aspirin therapy (100 mg daily) for an average of five years before their stroke. Of these, 26 (28.9%) were aspirin resistant, defined by more than 550 aspirin-reaction units (ARU) on the rapid platelet-function assay VerifyNow (Accumetrics).

Aspirin resistance was significantly associated with stroke severity as measured by National Institutes of Health Stroke Scale (NIHSS) scores, the researchers report. The median NIHSS score was 11 in aspirin-resistant patients compared with 4 in aspirin-sensitive patients, resulting in a significant median difference of 7 (95% CI 4.69-9.31; p<0.001).

Every 1-point increase in ARU was associated with a significant 0.03-point increase in NIHSS score (95% CI 0.01-0.04; p<0.001). This corresponded to an approximate median increase of 1 point in NIHSS score for every 33-point increase in ARU.

Aspirin resistance was also significantly associated with larger infarct size, as evidenced by lower Alberta Stroke Program Early CT Score (ASPECTS). "To our knowledge, this is a novel finding and has not been previously described," according to the authors.

The median ASPECTS was 5.5 in aspirin-resistant patients compared with 10 in aspirin-sensitive patients. Every 1-point increase in ARU was associated with a 0.02-point decrease in ASPECTS (95% CI -0.03 to -0.01; p<0.001), corresponding to a median decrease of 1 point in ASPECTS for every 50-point increase in ARU.

Yan and colleagues note that aspirin resistance was more common in current or former smokers. This may be due to worsening of platelet aggregability by cigarette smoking in patients receiving aspirin.

Previous MI, transient ischemic attack, or stroke was also significantly more prevalent in the aspirin-resistant group (odds ratio 8.04; 95% CI 2.89-22.3; p=0.001).

Routine platelet-function testing?

This is an "interesting" but "relatively small" study, commented Dr Philip B Gorelick (Michigan State University College of Human Medicine, Grand Rapids), who wasn't involved in the study.

"The small numbers of study subjects and other factors such as adherence to cardiovascular prevention medications, achievement of control targets, and type of cardiovascular prevention medications could be factors that influence the risk of and potentially the size of cerebral infarction and overall clinical outcome," Gorelick said.

"Furthermore, study results of serial measures of point-of-care platelet-function testing might be useful to validate that 'resistance' has consistently occurred or not. Despite these potential limitations, the study raises important questions about the effectiveness of aspirin in a subset of patients who may not have adequate platelet inhibition when aspirin is administered."

According to Gorelick, it's also important to "keep in mind that despite decades of discussion about platelet-function testing as it might be applied in practice and in relation to aspirin specifically, major guideline statements have not as of yet mandated such testing as a practice standard."

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