Aspirin Resistance Tied to Larger, More Severe Stroke

Megan Brooks

November 20, 2012

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.

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

Their findings were published online November 19 in Archives of Neurology.

A Novel Finding

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

In this study, researchers tested for aspirin resistance among 90 patients with acute ischemic stroke who had been receiving aspirin therapy (100 mg daily) for an average of 5 years before 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 indicated by higher National Institutes of Health Stroke Scale (NIHSS) scores in this group, the researchers report. The median NIHSS score was 11 (interquartile range [IQR], 4 - 16) in aspirin-resistant patients compared with 4 (IQR, 2 - 6) in aspirin-sensitive patients, resulting in a statistically significant median difference of 7 (95% confidence interval [CI], 4.69 - 9.31; P < .001).

Every 1-point increase in ARU was associated with a statistically significant 0.03-point increase in NIHSS score (95% CI, 0.01 - 0.04; P = .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," the researchers say.

The median ASPECTS was 5.5 (IQR, 4 - 6.5) in aspirin-resistant patients and 10 (IQR, 8 - 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 < .001), corresponding to a median decrease of 1 point in ASPECTS for every 50-point increase in ARU.

Dr. Yan and colleagues note that aspirin resistance was more common in current or former smokers. This may have resulted from cigarette smoking increasing platelet aggregability in patients receiving aspirin.

Previous myocardial infarction, 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 = .001).

Routine Platelet Function Testing?

This is an "interesting" but "relatively small" study, commented Philip B. Gorelick, MD, MPH, medical director of the Hauenstein Neuroscience Center at Saint Mary's Healthcare and professor in the Department of Translational Science and Molecular Medicine at Michigan State University College of Human Medicine in Grand Rapids. Dr. Gorelick was not 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," Dr. Gorelick told Medscape Medical News.

"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," Dr. Gorelick said.

He said 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."

Dr. Yan has disclosed no relevant financial relationships. One study author received honoraria from Biometrictra, the Australian distributor of VerifyNow, for educational presentations. Dr. Gorelick is a member of the ARRIVE (Aspirin to Reduce Risk of Initial Vascular Events) Steering Committee. The ARRIVE study is sponsored by Bayer.

Arch Neurol. Published online November 19, 2012. Abstract