TY - JOUR
T1 - Resistance to antiplatelet drugs
T2 - What progress has been made?
AU - Tantry, Udaya S.
AU - Gesheff, Martin
AU - Liu, Fang
AU - Bliden, Kevin P.
AU - Gurbel, Paul A.
N1 - Funding Information:
This paper has been supported by the Sinai Centre for Thrombosis Research. PA Gurbel reports serving as a consultant for Daiichi Sankyo, Lilly, Bayer, AstraZeneca, Accumetrics, Boehringer Ingelheim, Merck and Haemonetics; receiving grants from the National Institutes of Health, Daiichi Sankyo, Lilly, CSL, AstraZeneca, Harvard Clinical Research Institute, Haemonetics and Duke Clinical Research Institute; receiving payment for lectures, including service on speakers’ bureaus, from Lilly, Daiichi Sankyo and Merck. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
Publisher Copyright:
© 2014 Informa, Ltd.
PY - 2014/12/1
Y1 - 2014/12/1
N2 - Introduction: Despite well-documented efficacy, recurrent thrombotic event occurrences, particularly stent thrombosis, have been repeatedly demonstrated in stented patients treated with aspirin and clopidogrel. The latter observation stimulated the close scrutiny of the pharmacodynamic effects of clopidogrel and revealed the 'wide variability' and the phenomenon of 'antiplatelet resistance'. High on-treatment platelet reactivity to ADP (HPR) during clopidogrel therapy is an independent risk factor for ischemic event occurrences in post-percutaneous coronary intervention (post-PCI) patients. Recent observational studies demonstrated a link between low on-treatment platelet reactivity to bleeding. The concept of a 'therapeutic window' of P2Y12 receptor reactivity associated with both ischemic event occurrence (upper threshold) and bleeding risk (lower threshold) has been proposed. Areas covered: An update on and a brief review of the current knowledge on antiplatelet resistance were presented. Evidence available from studies evaluating aspirin resistance and high and low on-treatment platelet reactivity to ADP during P2Y12 receptor blocker therapy was collected from a selective literature search. Expert opinion: The available evidence indicates that HPR is an independent risk factor for post-PCI ischemic event occurrences. The therapeutic window concept for the P2Y12 receptor blocker therapy may facilitate the balance between reducing ischemic events and avoiding bleeding events, thereby improving net clinical outcome.
AB - Introduction: Despite well-documented efficacy, recurrent thrombotic event occurrences, particularly stent thrombosis, have been repeatedly demonstrated in stented patients treated with aspirin and clopidogrel. The latter observation stimulated the close scrutiny of the pharmacodynamic effects of clopidogrel and revealed the 'wide variability' and the phenomenon of 'antiplatelet resistance'. High on-treatment platelet reactivity to ADP (HPR) during clopidogrel therapy is an independent risk factor for ischemic event occurrences in post-percutaneous coronary intervention (post-PCI) patients. Recent observational studies demonstrated a link between low on-treatment platelet reactivity to bleeding. The concept of a 'therapeutic window' of P2Y12 receptor reactivity associated with both ischemic event occurrence (upper threshold) and bleeding risk (lower threshold) has been proposed. Areas covered: An update on and a brief review of the current knowledge on antiplatelet resistance were presented. Evidence available from studies evaluating aspirin resistance and high and low on-treatment platelet reactivity to ADP during P2Y12 receptor blocker therapy was collected from a selective literature search. Expert opinion: The available evidence indicates that HPR is an independent risk factor for post-PCI ischemic event occurrences. The therapeutic window concept for the P2Y12 receptor blocker therapy may facilitate the balance between reducing ischemic events and avoiding bleeding events, thereby improving net clinical outcome.
KW - Aspirin resistance
KW - Bleeding
KW - Clopidogrel resistance
KW - High on-treatment platelet reactivity
KW - Ischemic event occurrence
KW - Low on-treatment platelet reactivity
KW - Percutaneous coronary intervention
KW - Therapeutic window concept
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U2 - 10.1517/14656566.2014.968126
DO - 10.1517/14656566.2014.968126
M3 - Review article
C2 - 25297833
AN - SCOPUS:84910029915
SN - 1465-6566
VL - 15
SP - 2553
EP - 2564
JO - Expert opinion on pharmacotherapy
JF - Expert opinion on pharmacotherapy
IS - 17
ER -