Dual antiplatelet response during PCI: VerifyNow P2Y12 predicts myocardial necrosis and thromboxane B2 generation confirms wide variation in aspirin response.
BACKGROUND
There remains concern that the antiplatelet effects of aspirin and clopidogrel vary between patients and poor responders may be at increased risk of adverse events. However, the optimal method of measuring aspirin and/or clopidogrel response remains unresolved. We compared three methods of measuring clopidogrel response recommended by a recent consensus statement for the European Society of Cardiology, and investigated a novel approach to measuring aspirin response in patients established on both aspirin and clopidogrel. In addition, we investigated whether any of these assays predict peri-procedural myocardial necrosis following percutaneous coronary intervention (PCI).


METHODS
A cross-section of 323 patients attending for PCI was tested for clopidogrel response using VerifyNow P2Y12, VASP Platelet Reactivity Index (VASP-PRI) and whole blood impedance aggregometry (WBPA). Aspirin response was assessed by measuring the residual ability of platelets to generate thromboxane, calculated as the difference between thromboxane B2 levels in serum and plasma, [TxB2]S-P. Peri-procedural myocardial necrosis was determined by a change in troponin I >0.2 μmol/l.


RESULTS
Patients demonstrated wide variation in response to both aspirin and clopidogrel. Correlation between VerifyNow P2Y12 and VASP-PRI was good (r=0.702, p<0.001). Correlation was moderate between WBPA and VerifyNow P2Y12 (r=0.639, p<0.001) and weak for WBPA and VASP-PRI (r=0.353, p<0.001). Only VerifyNow P2Y12 predicted peri-procedural myocardial necrosis.


CONCLUSIONS
The three methods of measuring response to clopidogrel identify different patients as poor responders. Poor response to clopidogrel assessed by VerifyNow P2Y12 predicts myocardial necrosis. Measurement of [TxB2]S-P demonstrates a wide variation in aspirin response in patients taking dual antiplatelet therapy.
BHF Glasgow Cardiovascular Research Centre, University of Glasgow, UK; Golden Jubilee National Hospital, Department of Cardiology, Clydebank, Glasgow, UK.
Richard I S
RI
Good
BHF Glasgow Cardiovascular Research Centre, University of Glasgow, UK.
Anne
A
McGarrity
Department of Cardiovascular Sciences, University of Leicester and NIHR Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, UK.
Tina E
TE
James
BHF Glasgow Cardiovascular Research Centre, University of Glasgow, UK.
Helen
H
Miller
Robertson Centre for Biostatistics, University of Glasgow, UK.
Alex
A
McConnachie
Department of Cardiovascular Sciences, University of Leicester and NIHR Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, UK.
Alison H
AH
Goodall
Golden Jubilee National Hospital, Department of Cardiology, Clydebank, Glasgow, UK. Electronic address: Keith.Oldroyd@nhs.net.
Keith G
KG
Oldroyd
D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D001241:Aspirin / Q000627:therapeutic use*; D001792:Blood Platelets / Q000187:drug effects; D000077144:Clopidogrel; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000473:pathology*; D009336:Necrosis / Q000473:pathology*; D062645:Percutaneous Coronary Intervention / Q000379:methods*; D010974:Platelet Aggregation; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D010979:Platelet Function Tests; D058925:Receptors, Purinergic P2Y12 / Q000737:chemistry*; D012044:Regression Analysis; D013929:Thromboxane B2 / Q000737:chemistry / Q000378:metabolism*; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000627:therapeutic use
D000894:Anti-Inflammatory Agents, Non-Steroidal; C548576:P2RY12 protein, human; D010975:Platelet Aggregation Inhibitors; D058925:Receptors, Purinergic P2Y12; D013929:Thromboxane B2; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin
Aspirin; Coronary artery disease; P2Y12 antagonists; Percutaneous coronary intervention; Platelet function tests