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High Residual Platelet Reactivity and Thrombotic Events

Thomas Cuisset, MD, PhD; Pierre-Emmanuel Morange, MD, PhD; Marie-Christine Alessi, MD, PhD
[+] Author Affiliations

Author Affiliations: Inserm 626, Faculté de Médecine, Marseille, France (Marie-christine.alessi@univmed.fr).


JAMA. 2011;306(23):2561-2562. doi:10.1001/jama.2011.1838
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To the Editor: The study by Dr Parodi and colleagues showed an association between high residual platelet reactivity (HRPR) status after clopidogrel loading in patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndromes and ischemic events, despite adjusting therapy with higher clopidogrel dosing or switching to ticlopidine.1 Previous studies also found that HRPR, defined by adenosine diphosphate (ADP)-induced aggregometry above 70%, was associated with clinical outcomes after PCI for acute coronary syndromes,2 but these studies were observational and did not adjust therapy. These results confirmed those of the GRAVITAS (Gauging Responsiveness with A VerifyNow assay-Impact on Thrombosis And Safety) study, showing in a lower risk population that increased clopidogrel dosing was not effective in improving clinical outcomes of patients with initial HRPR.3 A limitation of the study is the absence of P2Y12 blocker use in patients with HRPR.

The authors tailored long-term antiplatelet therapy based on a single platelet test performed early (12-18 hours) after the loading dose in the unstable clinical setting of acute coronary syndromes. However, one study suggested that 1-month platelet reactivity might be a better predictor of long-term clinical outcome than platelet reactivity measured at initial assessment.4 This study also showed that agreement between initial response and chronic steady-state assessment of platelet reactivity was weak. Tailoring therapy based on a single test after the loading dose therefore might lead to overtreatment with higher doses or new agents of patients with adequate platelet reactivity while receiving clopidogrel or undertreatment with standard therapy of patients with HRPR who might require alternative strategies. The timing (too early) of the test leading to tailored therapy and the strategy chosen in patients with HRPR (no P2Y12 blockers) might have partially explained results of the study.

AUTHOR INFORMATION

Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Drs Cuisset, Morange, and Alessi reported having received a research grant from Eli Lilly for work on pharmacologic platelet inhibition. Dr Cuisset reported receiving consulting fees from Daiichi-Sankyo and Eli Lilly, research grants from Daiichi-Sankyo and Eli Lilly, travel support from Boston Scientific, Medtronic, Abbott Vascular, Servier, and Cordis; and lecture fees from AstraZeneca, Abbott Vascular, Biotronik, Boston Scientific, Cordis, Daiichi-Sankyo, Eli Lilly, sanofi-aventis, and Servier. Dr Morange reported receiving grants from Stago for the development of new hemostasis assays and from sanofi-aventis for a study on fibrinolysis. Dr Alessi reported being a consultant to Stago for new drug development and sanofi-aventis for assay development.

REFERENCES

Parodi G, Marcucci R, Valenti R,  et al.  High residual platelet reactivity after clopidogrel loading and long-term cardiovascular events among patients with acute coronary syndromes undergoing PCI.  JAMA. 2011;306(11):1215-1223
PubMed
Cuisset T, Frere C, Quilici J,  et al.  High post-treatment platelet reactivity identified low-responders to dual antiplatelet therapy at increased risk of recurrent cardiovascular events after stenting for acute coronary syndrome.  J Thromb Haemost. 2006;4(3):542-549
PubMed
Price MJ, Berger PB, Teirstein PS,  et al; GRAVITAS Investigators.  Standard- vs high-dose clopidogrel based on platelet function testing after percutaneous coronary intervention: the GRAVITAS randomized trial [published correction appears in JAMA. 2011;305(21):2174].  JAMA. 2011;305(11):1097-1105
PubMed
Campo G, Parrinello G, Ferraresi P,  et al.  Prospective evaluation of on-clopidogrel platelet reactivity over time in patients treated with percutaneous coronary intervention relationship with gene polymorphisms and clinical outcome.  J Am Coll Cardiol. 2011;57(25):2474-2483
PubMed

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Parodi G, Marcucci R, Valenti R,  et al.  High residual platelet reactivity after clopidogrel loading and long-term cardiovascular events among patients with acute coronary syndromes undergoing PCI.  JAMA. 2011;306(11):1215-1223
PubMed
Cuisset T, Frere C, Quilici J,  et al.  High post-treatment platelet reactivity identified low-responders to dual antiplatelet therapy at increased risk of recurrent cardiovascular events after stenting for acute coronary syndrome.  J Thromb Haemost. 2006;4(3):542-549
PubMed
Price MJ, Berger PB, Teirstein PS,  et al; GRAVITAS Investigators.  Standard- vs high-dose clopidogrel based on platelet function testing after percutaneous coronary intervention: the GRAVITAS randomized trial [published correction appears in JAMA. 2011;305(21):2174].  JAMA. 2011;305(11):1097-1105
PubMed
Campo G, Parrinello G, Ferraresi P,  et al.  Prospective evaluation of on-clopidogrel platelet reactivity over time in patients treated with percutaneous coronary intervention relationship with gene polymorphisms and clinical outcome.  J Am Coll Cardiol. 2011;57(25):2474-2483
PubMed
December 21, 2011
Renato Valenti, MD; Guido Parodi, MD; David Antoniucci, MD
JAMA. 2011;306(23):2561-2562. doi:10.1001/jama.2011.1839.
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