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European Heart Journal Advance Access published online on July 9, 2008
European Heart Journal, doi:10.1093/eurheartj/ehn313
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Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2008. For permissions please email: journals.permissions@oxfordjournals.org
The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that the original authorship is properly and fully attributed; the Journal, Learned Society and Oxford University Press are attributed as the original place of publication with correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions@oxfordjournals.org.

The optimal threshold of high post-treatment platelet reactivity could be defined by a point-of-care VerifyNow P2Y12 assay

Young-Hoon Jeong

Division of Cardiology
Department of Internal Medicine
Gyeongsang National University Hospital
90 Chiram-dong
Jinju 660-702
South Korea
Tel: + 82 55 750 8065
Fax: + 82 55 758 9122
Email: goodoctor{at}naver.com

In-Suk Kim

Department of Laboratory Medicine
Gyeongsang National University Hospital
Jinju
South Korea

Bong-Ryong Choi

Division of Cardiology
Department of Internal Medicine
Gyeongsang National University Hospital
Jinju
South Korea

Choong Hwan Kwak

Division of Cardiology
Department of Internal Medicine
Gyeongsang National University Hospital
Jinju
South Korea

Jin-Yong Hwang

Division of Cardiology
Department of Internal Medicine
Gyeongsang National University Hospital
Jinju
South Korea

We read with great interest the study by Price et al.,1 which verifies that high post-treatment platelet reactivity (HPPR) measured with a point-of-care VerifyNow assay (Accumetrics Inc., San Diego, CA, USA) is associated with post-discharge events after percutaneous coronary intervention (PCI) with drug-eluting stent (DES), including stent thrombosis. To the best of our knowledge, this is the first study to identify a threshold of HPPR of VerifyNow based on the clinical outcomes.

Recently, a number of studies have demonstrated that clopidogrel non-responsiveness proven in the laboratory testing, i.e. HPPR, has been associated with an increased risk for cardiovascular events.2 Light transmittance aggregometry (LTA) is the gold standard test to determine the clopidogrel responsiveness. However, the abundant demands of LTA make it difficult to utilize in daily practice. VerifyNow was developed as a point-of-care test and showed a significant correlation with ADP-induced LTA (r = 0.64 – 0.73).3

In previous studies using LTA, platelet aggregation of >50% induced by 5 µM ADP4 or of >70% induced by 10 µM ADP5 has been suggested an absolute threshold of HPPR for predicting the ischaemic outcomes. In the study of Price et al., the optimal cut-off for the combined endpoint was a post-treatment reactivity of ≥235 PRU (P2Y12 reactivity unit) (area under curve [AUC] 0.711, 95% confidence interval [CI] 0.529–0.893, P = 0.03). Because this study did not show the association between the HPPRs by a point-of-care test and ADP-induced LTA, we estimated the relation using our data. Three hundred consecutive patients undergoing PCI with DES implantation at our hospital were enrolled between October 2007 and March 2008. We performed 5 µM ADP-induced LTA and VerifyNow using the same blood sampling via the arterial sheath. LTA was performed in all patients according to standard protocols.6 Both PRU (r = 0.641, P < 0.001) and percentage platelet inhibition (r = 0.679, P < 0.001) measured by VerifyNow had significant correlations with the results of 5 µM ADP-induced platelet aggregation. By the receiver-operating characteristics curve analysis, the optimal cut-off for predicting HPPR on LTA (5 µM ADP-induced platelet aggregation >50%) was PRU ≥ 239 (AUC 0.794, 95% CI 0.736–0.851, P < 0.001). The PRU value ≥ 239 showed a sensitivity of 83.6% and a specificity of 68.3%, and was similar to the threshold of high reactivity value (PRU ≥ 235), suggested by Price et al.1 The percentage platelet inhibition of ≤20 was the optimal cut-off for predicting HPPR on LTA (AUC 0.841, 95% CI 0.790–0.891, P < 0.001), which showed a sensitivity of 76.2% and a specificity of 83.6%.

A VerifyNow assay has been used widely in the daily practice instead of LTA. However, its usefulness for predicting adverse cardiovascular events has been still undetermined. On the basis of our data analysis, we could ascertain that high platelet reactivity on VerifyNow (PRU ≥ 235 suggested by Price et al.) is significantly correlated with HPPR on ADP-induced LTA. It might suggest a substitutability of VerifyNow in terms of assessment of clopidogrel responsiveness and practical implication for risk stratification.

Funding to pay the Open Access publication charges for this article was provided by J.-Y. Hwang, the senior of the Cardiology Division.

References

  1. Price MJ, Endemann S, Gollapudi RR, Valencia R, Stinis CT, Levisay JP, Ernst A, Sawhney NS, Schatz RA, Teirstein PS. Prognostic significance of post-clopidogrel platelet reactivity assessed by a point-of-care assay on thrombotic events after drug-eluting stent implantation. Eur Heart J (2008) 29:992–1000.[Abstract/Free Full Text]
  2. Snoep JD, Hovens MM, Eikenboom JC, van der Bom JG, Jukema JW, Huisman MV. Clopidogrel nonresponsiveness in patients undergoing percutaneous coronary intervention with stenting: a systematic review and meta-analysis. Am Heart J (2007) 154:221–231.[CrossRef][Web of Science][Medline]
  3. Paniccia R, Antonucci E, Gori AM, Marcucci R, Giglioli C, Antoniucci D, Gensini GF, Abbate R, Prisco D. Different methodologies for evaluating the effect of clopidogrel on platelet function in high-risk coronary artery disease patients. J Thromb Haemost (2007) 5:1839–1847.[CrossRef][Web of Science][Medline]
  4. Bliden KP, DiChiara J, Tantry US, Bassi AK, Chaganti SK, Gurbel PA. Increased risk in patients with high platelet aggregation receiving chronic clopidogrel therapy undergoing percutaneous coronary intervention: is the current antiplatelet therapy adequate? J Am Coll Cardiol (2007) 49:657–666.[Abstract/Free Full Text]
  5. Buonamici P, Marcucci R, Migliorini A, Gensini GF, Santini A, Paniccia R, Moschi G, Gori AM, Abbate R, Antoniucci D. Impact of platelet reactivity after clopidogrel administration on drug-eluting stent thrombosis. J Am Coll Cardiol (2007) 49:2312–2317.[Abstract/Free Full Text]
  6. Angiolillo DJ, Shoemaker SB, Desai B, Yuan H, Charlton RK, Bernardo E, Zenni MM, Guzman LA, Bass TA, Costa MA. Randomized comparison of a high clopidogrel maintenance dose in patients with diabetes mellitus and coronary artery disease: results of the Optimizing Antiplatelet Therapy in Diabetes Mellitus (OPTIMUS) study. Circulation (2007) 115:708–716.[Abstract/Free Full Text]

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This Article
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