Relation between impaired antiplatelet response to clopidogrel and possible pleiotropic effects.
BACKGROUND
The study was designed to determine whether impaired antiplatelet response to clopidogrel but not to aspirin may be responsible for loss of pleiotropic effects of the drug.


METHODS
Study included 34 consecutive patients with STEMI undergoing primary percutaneous coronary intervention (PCI) with stent implantation treated with aspirin (loading dose 300 mg followed by 75 mg/day) and clopidogrel (loading dose 600 mg followed by 75 mg/day). On the basis of Platelet Function Analyzer (PFA)-100 test which measured closure times (CT) in test with collagen/epinephrine (CEPI-CT) or collagen/adenosine diphosphate (CADP-CT) patients were stratified after 7 days from admission as full aspirin or clopidogrel responders (CEPI-CT or CADP-CT = 300 sec., respectively) and non-full aspirin or clopidogrel responders (CEPI-CT or CADP-CT < 300 sec., respectively). High sensitivity C-reactive protein (hs-CRP) was measured at baseline and after 7 days of treatment.


RESULTS
All patients received comparable statin treatment. Median and interquartile ranges (IQR) of hs-CRP increased significantly from 2.5 mg/L (0.4-44.8) at baseline to 8.05 mg/L (1.4-33.9) at day 7 (P = .002) in non-full clopidogrel responders subgroup and only slightly in the full clopidogrel responders subgroup (2.45 mg/L, IQR 0.4-48.3 vs. 4.2 mg/L, IQR 1.9-17.5) (P = .3) remaining within reference intervals. On the contrary median and IQR of hs-CRP increased significantly in both non-full aspirin responders (2.4 mg/L, IQR 1.3-3.3 vs. 5.8 mg/L, IQR 3.2-14.8, P = .01) and full aspirin responders (2.9 mg/L, IQR 2.0-3.7 vs. 5.6 mg/L, IQR 4.3-12.9, P = .04).


CONCLUSIONS
Impaired antiplatelet response to clopidogrel but not to aspirin may contribute to smaller anti-inflammatory response in patients with ST-elevation myocardial infarction.
Malek
Lukasz A
LA
1st Department of Cardiology, Medical University of Warsaw, 1a Banacha Str, Warsaw 02-097, Poland. lamalek@amwaw.edu.pl
Grabowski
Marcin
M
Spiewak
Mateusz
M
Filipiak
Krzysztof J
KJ
Szpotanska
Monika
M
Imiela
Tomasz
T
Huczek
Zenon
Z
Bobilewicz
Dagna
D
Opolski
Grzegorz
G
D000368:Aged; D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects*; D002097:C-Reactive Protein / Q000187:drug effects*; D000077144:Clopidogrel; D004351:Drug Resistance; D005260:Female; D006801:Humans; D007249:Inflammation / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000601:surgery; D010975:Platelet Aggregation Inhibitors / Q000276:immunology / Q000494:pharmacology*; D010979:Platelet Function Tests; D015607:Stents; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000276:immunology / Q000494:pharmacology
D010975:Platelet Aggregation Inhibitors; D002097:C-Reactive Protein; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin