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Residual platelet reactivity to predict long-term clinical outcomes after clopidogrel loading in patients with acute coronary syndromes: comparison of different cutoff values by light transmission aggregometry from the responsiveness to clopidogrel and stent thrombosis 2-acute coronary syndrome (RECLOSE 2-ACS) study

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Abstract

The aim of this study was the identification of the optimal cutoff value of high residual platelet reactivity (HRPR) assessed by light transmission aggregometry (LTA) in the responsiveness to clopidogrel and stent thrombosis 2-acute coronary syndrome (RECLOSE 2-ACS) patient cohort to discriminate patients with and without major adverse cardiac events (MACE) and cardiac death at 2 years. The RECLOSE 2-ACS study included 1,789 patients with ACS who underwent LTA after clopidogrel loading. A post hoc cutoff value for HRPR was defined with the ROC curve and the Youden index and compared with the protocol-defined cutoff of 70 %. By ROC analysis, 63 % resulted the optimal cutoff value to predict both MACE and cardiac death at 2 years follow-up. A significant sensitivity improvement for the ROC-based cutoff value was noted (p < 0.001), at the price of lower specificity and predictive accuracy. The latter were 81 % for MACE and 85 % for cardiac death with the 70 % cutoff, while the respective figures were 73 and 75 % with the 63 % cutoff. The areas under the curve were virtually identical with the 70 and 63 % cutoffs both for MACE (0.71) and cardiac death (0.79). A residual platelet reactivity cutoff of 70 % by LTA, compared to the ROC-based cutoff of 63 %, allows for the identification of a subset of patients at very high risk of adverse ischemic events, making LTA-ADP test more acceptable in clinical practice for the identification of subjects at risk than other platelet function assays with broader definitions of HRPR.

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Acknowledgments

This work was supported by an unrestricted grant from the Italian Health Ministry to the Tuscany Region for the Finalized Medical Research Program 2007. The sponsor had no role in the design and management of the study or in the analysis and interpretation of the data, or in the preparation, review, or approval of the manuscript.

Conflict of interests

Dr. Antoniucci reported receiving consulting fees from Daiichi Sankyo/Eli Lilly, The Medicines Company, and serving on the advisory board of Cordis and CID. Dr. Parodi reported receiving consulting fees from Daiichi Sankyo/Eli Lilly. Dr. Gensini reports receiving consulting fees from Bayer, Boehringer Ingelheim, Eli Lilly; lecture fees from Astra Zeneca, GlaxoSmithKline, Instrumentation Laboratory, Menarini, and Sigma Tau; research grant funding from Novo Nordisk, Merck Sharp Dohme, Pfizer, Pierrel, Sanofi Aventis, and Servier. Dr. Abbate reports receiving consulting fees from Eli Lilly; lecture fees from Instrumentation Laboratory, and Sigma Tau; research grant funding from Bayer, Boehringer Ingelheim, and Pfizer. Dr. Marcucci received honoraria for lectures from Daiichi Sankyo/Eli Lilly and Merck Sharp Dohme. Dr. Capodanno has received payments as an individual for consulting fee or honorarium from Eli Lilly, Daiichi Sankyo, The Medicines Company, and AstraZeneca. The other authors reported no disclosures.

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Authors and Affiliations

  1. Division of Cardiology, Department of Cardiology, Careggi Hospital, Viale Pieraccini 17, 50134, Florence, Italy

    Renato Valenti, Rossella Marcucci, Angela Migliorini, Anna Maria Gori, Guido Parodi, Betti Giusti, Nazario Carrabba, Rita Paniccia, Giulia Cantini, Marco Marrani, Gian Franco Gensini, Rosanna Abbate & David Antoniucci

  2. Cardiovascular Department, Ferrarotto Hospital, University of Catania, Catania, Italy

    Davide Capodanno

  3. Division of Cardiology, ‘Maggiore della Carità’ Hospital, Eastern Piedmont University, Novara, Italy

    Giuseppe De Luca

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  1. Renato Valenti
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  2. Rossella Marcucci
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  3. Davide Capodanno
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  4. Giuseppe De Luca
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  5. Angela Migliorini
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  6. Anna Maria Gori
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  7. Guido Parodi
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  8. Betti Giusti
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  9. Nazario Carrabba
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  10. Rita Paniccia
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  11. Giulia Cantini
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  12. Marco Marrani
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  13. Gian Franco Gensini
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  15. David Antoniucci
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Correspondence to David Antoniucci.

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Valenti, R., Marcucci, R., Capodanno, D. et al. Residual platelet reactivity to predict long-term clinical outcomes after clopidogrel loading in patients with acute coronary syndromes: comparison of different cutoff values by light transmission aggregometry from the responsiveness to clopidogrel and stent thrombosis 2-acute coronary syndrome (RECLOSE 2-ACS) study. J Thromb Thrombolysis 40, 76–82 (2015). https://doi.org/10.1007/s11239-014-1159-1

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  • DOI: https://doi.org/10.1007/s11239-014-1159-1

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