European Heart Journal Advance Access originally published online on April 15, 2008
European Heart Journal 2008 29(11):1471; doi:10.1093/eurheartj/ehn158
How to react to high platelet reactivity?
Department of Cardiology
Radboud University Nijmegen Medical Centre
Geert Grooteplein Zuid 8
Nijmegen 6525 GA
The Netherlands
Tel: +31 24 361 6785
Fax: +31 24 354 0800
Email: n.clappers{at}cardio.umcn.nl
Department of Cardiology
Radboud University Nijmegen Medical Centre
Geert Grooteplein Zuid 8
Nijmegen 6525 GA
The Netherlands
Department of Cardiology
Radboud University Nijmegen Medical Centre
Geert Grooteplein Zuid 8
Nijmegen 6525 GA
The Netherlands
With interest we read the article on the prognostic significance of high platelet reactivity as measured with the VerifyNow P2Y12 assay for atherothrombotic events after coronary stenting.1 We compliment the authors on their methodology. In contrast to many previous reports, they did not use a prospectively chosen cut-off value with subsequent clinical follow-up. Inherent to ROC analysis, the observed cut-off value in the present report is based on the optimal clinical discrimination between higher and lower risk patients. We believe that this is an essential step that should also be taken in other studies investigating platelet reactivity in relation to thrombotic events. Presently, no clinically based cut-off values are available for patients on (dual) antiplatelet therapy, and no test has been consistently validated in prospective studies on clinical events. Unfortunately, the cut-offs in most of the previous reports are arbitrarily chosen, supplied by the manufacturer, or even reflect values derived in subjects not using antiplatelet therapy.
The finding that high platelet reactivity on the VerifyNow P2Y12 assay is related to an increased risk of thrombotic events is theoretically appealing, but whether it provides extra information in the risk stratification in clinical practice remains to be proven. We therefore feel that the term ‘prognostic significance’ in the article by Price et al. is somewhat unfortunate.1 In fact, the positive predictive value of the reported increased platelet reactivity is low, partly as a result of the low event rate. The report suggests only a univariate statistical association between higher platelet reactivity and events. The baseline characteristics show that the patients with high platelet reactivity more frequently had important clinical risk factors for death and myocardial infarction: diabetes mellitus, older age, renal insufficiency, and heart failure.2 Moreover, renal insufficiency and diabetes mellitus are also strong and independent risk factors for stent thrombosis.3 The question is whether the significant association between high platelet reactivity and the increased risk of clinical events would persist after appropriate multivariate analysis. In addition to the methodology regarding the cut-off levels, we believe that future studies on this subject should carefully account for clinical, angiographic, and procedural parameters associated with the primary endpoint. In view of the above, we need to verify in future larger scale studies whether the VerifyNow P2Y12 assay offers additional prognostic information on top of classical risk stratification based on clinical parameters.
References
- Price MJ, Endemann S, Gollapudi RR, Valencia R, Stinis CT, Levisay JP, et al. 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] - Daly CA, De SB, Sendon JL, Tavazzi L, Boersma E, Clemens F, et al. Predicting prognosis in stable angina—results from the Euro heart survey of stable angina: prospective observational study. BMJ (2006) 332:262–267.
[Abstract/Free Full Text] - Iakovou I, Schmidt T, Bonizzoni E, Ge L, Sangiorgi GM, Stankovic G, et al. Incidence, predictors, and outcome of thrombosis after successful implantation of drug-eluting stents. JAMA (2005) 293:2126–2130.
[Abstract/Free Full Text]
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