Aspirin response evaluated by the VerifyNow™ Aspirin System and Light Transmission Aggregometry

doi:10.1016/j.thromres.2008.03.023

Thrombosis Research

Volume 123, Issue 2, December 2008, Pages 267-273

https://doi.org/10.1016/j.thromres.2008.03.023 Get rights and content

Abstract

Introduction

Patients with inadequate platelet inhibition by aspirin, referred to as aspirin resistance, might have an increased risk of suffering cardiovascular events. Therefore, identification of these patients by measuring platelet function is of great interest. Our objectives were to evaluate performance parameters of VerifyNow™ and to determine the agreement between VerifyNow™ and light transmission aggregometry (LTA) ad modum Born.

Materials and Methods

We included 21 healthy volunteers and 40 patients with stable coronary artery disease. Duplicate measurements of platelet aggregation were performed using VerifyNow™ and LTA (arachidonic acid 1.0 mM) in healthy volunteers before aspirin and in all participants on four consecutive days during treatment with non-enteric-coated aspirin 75 mg daily. VerifyNow™ test results were expressed in Aspirin Reaction Units (ARU) and LTA test results in percent of maximal aggregation. The cut-off for determination of aspirin resistance was ≥ 550 ARU and ≥ 20%, respectively.

Results

All participants were compliant, confirmed by complete suppression of serum-thromboxane B₂. VerifyNow™ was highly repeatable with a coefficient of variance of 0.5% at baseline and 3.0% during aspirin treatment. No individuals were identified as aspirin resistant with VerifyNow™, whereas seven (12%) individuals were identified with LTA. ROC analysis using LTA as the gold standard showed poor sensitivity and good specificity with a cut-off at 550 ARU.

Conclusion

VerifyNow™ was highly repeatable, but further studies are needed to investigate the relevance of the cut-off level at 550 ARU for detecting aspirin resistance.

Introduction

Low-dose aspirin inhibits platelet aggregation and is widely used in the treatment of cardiovascular disease [1]. Much variation is seen in the individual response to aspirin therapy [1], and a considerable proportion of patients demonstrate a normal platelet function despite daily aspirin treatment [2], [3]. Based on these findings, the terms “aspirin resistance” (AR) and “aspirin low-responsiveness” were introduced [4]. Previous studies report AR prevalences in healthy volunteers and in patients with various manifestations of atherosclerosis ranging from 6% to 63% depending on the method and the AR-definition used [4], [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16], [17].

Studies suggest that patients with insufficient platelet inhibition during aspirin therapy are at increased risk of suffering future vascular events [5], [6], [7], [18], [19], [20] and, obviously, the identification of these patients is of great interest.

At present, there is no established international consensus regarding measurement of platelet response to aspirin, and the available methods have several drawbacks. Light transmission aggregometry (LTA) a.m. Born is the classical method for measurement of platelet aggregation [21], but it is labour-intensive and time-consuming.

VerifyNow™ Aspirin is a new cartridge-based point-of-care platelet aggregation test designed to detect AR [22]. We conducted a study on healthy volunteers and patients with stable coronary artery disease (CAD) treated with 75 mg non-enteric-coated aspirin daily. Compliance was carefully controlled with face-to-face interviews, pill counting and serum thromboxane B₂ (se-TxB₂) measurements. Our aims were to examine the performance of the VerifyNow™ Aspirin System and to compare this point-of-care test with LTA.

Section snippets

Study population

The study population consisted of 21 healthy volunteers and 40 patients with stable CAD taking 75 mg of aspirin (Nycomed Denmark Aps) daily.

Healthy volunteers were eligible for the study if they were completely healthy and above the age of 18 years. They were excluded if they were intolerant to aspirin, had any chronic or acute disease, were taking any drug with known effect on platelet function (including NSAIDs), were smokers, were pregnant or had a platelet count < 120 × 10⁹/l. Patients were

Results

Clinical characteristics of the study population are shown in Table 1, Table 2. From pill counting and interviews it was concluded that all study participants were taking aspirin as prescribed, and this was confirmed by se-TxB₂ levels < 4.5 ng/ml.

Aggregation studies with the VerifyNow™ Aspirin system showed a high degree of repeatability on duplicates; the mean difference between duplicate measurements was 3 ARU (SD 3 ARU) at baseline and 12 ARU (SD 10 ARU) during aspirin therapy. For duplicate

Discussion

We found a very high repeatability of the VerifyNow™ Aspirin System, thus confirming previous studies [14], [38], [39]. In agreement with previous studies only a moderate correlation was found between aggregation analyses performed with the VerifyNow™ Aspirin using AA based cartridges and LTA_AA[9], [10], [13], [37], [38], [39]. In contrast, other studies have reported a good correlation between the two methods [14], [42], [43]. However, these studies all used cationic propyl gallate (cPG) as

Acknowledgements

The statistical support provided by Niels Trolle Andersen (Department of Biostatistics, Institute of Public Health, Aarhus University, Denmark) is highly appreciated.

We thank Accumetrics (San Diego, CA, USA) for the kind donation of the VerifyNow™ Aspirin test cartridges.

The assistance of the laboratory technicians at the Department of Clinical Biochemistry, Center for Haemophilia and Thrombosis is very much appreciated.

The study was financially supported by: Danish Research Agency (grant

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Aspirin forms a cornerstone of management in patients with established cardiovascular disease (CVD). Despite proven efficacy, variability of aspirin response has long been recognised, with early studies suggesting rates of high on treatment platelet reactivity (HTPR) as ranging between 5 and 45%. Whether aspirin responsiveness relates to long-term prognosis in patients with CVD is unknown.
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Time from aspirin loading (or admission on aspirin) to angiography was 4.9 ± 2.7 days. Platelet aggregation results, expressed as aspirin reaction units (ARU) were divided into tertiles: T1 (ARU 363–405) (n = 76), T2 (ARU 406–436) (n = 76), T3 (ARU 437–596) (n = 72). Higher ARU values were associated with increased mortality (log rank, p = 0.009), with those in the T3 having a 3-fold higher rate of events than those in the T1 (HR 3.03 [95% CI 1.33–6.99], p = 0.009) over a 10-year follow up.
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Citation Excerpt :
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Regular ArticleAspirin response evaluated by the VerifyNow™ Aspirin System and Light Transmission Aggregometry

Abstract

Introduction

Materials and Methods

Results

Conclusion

Introduction

Section snippets

Study population

Results

Discussion

Acknowledgements

Chest

Lancet

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Regular Article
Aspirin response evaluated by the VerifyNow™ Aspirin System and Light Transmission Aggregometry