Is the New Point-of-Care Test VerifyNow® Aspirin Able To Identify Aspirin Resistance Using the Recommended Cut-Off?.

Low dose aspirin inhibits platelet aggregation and is widely used in the treatment of cardiovascular disease. However, a considerable interindividuel variation in response to aspirin has been reported. Some studies suggest that patients with inadequate platelet inhibition by aspirin are at increased risk of suffering future cardiovascular events. Identification of these patients is of great interest. So far there is no consensus regarding the choice of method and definition for identifying patients with inadequate response to aspirin treatment, also referred to as aspirin resistance (AR). The VerifyNow® Aspirin system is a new point-of-care method for measurement of platelet aggregation response to aspirin. The main objectives were:

1. to determine the repeatability of VerifyNow® Aspirin

2. to determine the agreement between VerifyNow® and light transmission aggregometry (LTA) - the considered reference method

3. to determine the frequency of AR defined by the two methods.

We included 21 healthy volunteers and 40 patients with documented coronary artery disease. Duplicate measurements of platelet aggregation were performed with VerifyNow® Aspirin and LTA (agonist arachidonic acid 1.0 mM) in healthy volunteers before onset of aspirin treatment. After treatment of healthy volunteers with plain aspirin 75 mg daily for 7 days steady state was reached, and duplicate platelet aggregation measurements were performed once a day for four consecutive days in both healthy subjects and patients during continued treatment with plain aspirin 75 mg daily. Test results were expressed in Aspirin Reaction Units (ARU) using VerifyNow® Aspirin and in percent of max aggregation with LTA. The cut-off for determining AR was ≥ 550 ARU for VerifyNow® and ≥ 20% for LTA. To confirm compliance we measured serum-thromboxaneB₂ (se-TXB₂) levels. All participants were compliant to aspirin treatment as measured by se-TXB₂; < 4,5 ng/mL 99% suppression. All duplicate analyses with VerifyNow® showed a high degree of repeatability as the coefficient of variance prior to aspirin treatment was 0.5% and 3.0% during aspirin treatment. Correlation of measurements of platelet aggregation during aspirin therapy with VerifyNow® and LTA respectively was moderate, Spearmans ρ=0.50. The agreement between the two methods regarding identification of individuals with AR was poor: According to VerifyNow® Aspirin none of the participants had AR, whereas LTA identified 7 (12%) subjects with AR. We performed ROC analysis using LTA as reference method. We found poor sensitivity and good specificity when using 550 ARU as a cut-off, table.

In conclusion we found that VerifyNow® Aspirin showed a very high repeatability, but correlated only moderately well with LTA. In 100% compliant participants treated with a low dose of aspirin 75 mg daily we found that none of the study participants were classified as AR with VerifyNow® Aspirin, but 12% were identified as AR by LTA. Our results imply that the recommended cut-off level at 550 ARU for identifying AR with VerifyNow® Aspirin is too high. Further studies are needed to investigate the relevance of a cut-off level lower than 550 ARU for determining AR and its clinical implications.