Letter by de Miguel Castro et al Regarding Article, “Cardiovascular Death and Nonfatal Myocardial Infarction in Acute Coronary Syndrome Patients Receiving Coronary Stenting Are Predicted by Residual Platelet Reactivity to ADP Detected by a Point-of-Care Assay: A 12-Month Follow-Up”
To the Editor:
We read with great interest the article by Marcucci et al in a recent issue of Circulation.1 The authors concluded that a residual platelet reactivity (RPR) cutoff value ≥240 reaction units identified patients with a significantly higher risk of cardiovascular death and nonfatal myocardial infarction. Considering the potential clinical implications of this attractive study, addressing some methodological issues would be appreciated.
Although only patients with acute coronary syndrome were enrolled, the study population is somewhat heterogeneous because patients with ST-elevation myocardial infarction (STEMI), non-STEMI, and unstable angina were included. Patients with STEMI suffer from acute thrombus formation leading to total coronary artery occlusion. Greater platelet reactivity should be expected in this clinical condition. In the present study,1 a similar proportion of patients with STEMI were found in the high-RPR (28.7%) and low-RPR (27.5%) groups. Did the authors analyze differences in RPR mean values between patients with STEMI and the rest of the study population? It would be interesting to know whether the proposed cutoff value might be influenced by potential differences in RPR in different clinical conditions. Geisler et al2 showed different posttreatment platelet reactivity and response to dual antiplatelet therapy between patients with stable angina and those with acute coronary syndrome, supporting the concept that “the more severe the clinical condition, the higher the platelet reactivity.”
In the present study, RPR measurement was performed in some patients within 24 hours after 600 mg clopidogrel loading dose and in other patients (those who received glycoprotein IIb/IIIa inhibitors) 6 days after clopidogrel loading dose. Did the authors observe different RPR mean values between these 2 groups of patients? After intensive treatment, a delay in the measurement of platelet function to a subacute phase of the coronary event might influence platelet reactivity values.
In a series of patients with non-STEMI and unstable angina,3 we identified a RPR cutoff value of 175 reaction units as a predictor of 1-year adverse cardiovascular events. This cutoff value differs from that proposed by Marcucci et al1 and other authors.4,5 Differences in the composition of the study population and antithrombotic therapies can explain the difference, as does the prolonged period (69±30 hour) of intensive treatment before the angiography in our study group.
RPR is recognized as a better estimate for thrombotic risk than the inhibition of platelet aggregation, given that the latter does not take into account the absolute level of platelet reactivity. We absolutely agree with the authors that RPR is able to identify patients at higher risk of long-term adverse clinical events. Due to the limitations of available clinical studies and platelet function tests, proposed cutoff values should be applied with caution in different clinical conditions. Definitive data from large-scale clinical trials are needed to confirm these differences and to support a change in antiplatelet therapy based on the measurement of the platelet reactivity.
Work by the authors is supported by an unrestricted grant from the Health Research Foundation of Leon (Fundación Investigación Sanitaria en León).
Marcucci R, Gori AM, Paniccia R, Giusti B, Valente S, Giglioli C, Buonamici P, Antoniucci D, Abbate R, Gensini GF. Cardiovascular death and nonfatal myocardial infarction in acute coronary syndrome patients receiving coronary stenting are predicted by residual platelet reactivity to ADP detected by a point-of-care assay: a 12-month follow-up. Circulation. 2009; 119: 237–242.
Geisler T, Kapp M, Gohring-Frischholz K, Daub K, Dosch C, Bigalke B, Langer H, Herdeg C, Gawaz M. Residual platelet activity is increased in clopidogrel- and ASA-treated patients with coronary stenting for acute coronary syndromes compared with stable coronary artery disease. Heart. 2008; 94: 743–747.
de Miguel Castro A, Cuellas Ramon C, Diego Nieto A, Samaniego Lampon B, Alonso Rodriguez D, Fernandez Vazquez F, Alonso Orcajo N, Carbonell de Blas R, Pascual Vicente C, Perez de Prado A. Posttreatment platelet reactivity predicts long-term adverse events better than the response to clopidogrel in patients with non-ST-segment elevation acute coronary syndrome. Rev Esp Cardiol. 2009; 62: 126–135.
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.
Patti G, Nusca A, Mangiacapra F, Gatto L, D'Ambrosio A, Di Sciascio G. Point-of-care measurement of clopidogrel responsiveness predicts clinical outcome in patients undergoing percutaneous coronary intervention: results of the ARMYDA-PRO (antiplatelet therapy for reduction of myocardial damage during angioplasty-platelet reactivity predicts outcome) study. J Am Coll Cardiol. 2008; 52: 1128–1133.