Slow response to clopidogrel predicts low response.
OBJECTIVE
The purpose of this study was to determine whether the speed of response to clopidogrel loading predicts the final degree of response.


BACKGROUND
Fast inhibition of platelet aggregation is important in the setting of acute coronary syndromes and percutaneous coronary intervention, but its association with the final degree of inhibition is not well established.


METHODS
We performed a post hoc analysis of the ALBION study; early kinetic profiles of adenosine diphosphate 20 micromol/l maximal platelet aggregation (MPA) and DeltaMPA (with baseline sample as reference) were studied at 8 time points within the 24 h after clopidogrel loading (300, 600, or 900 mg) in non-ST-segment elevation acute coronary syndrome patients. Low response was defined as DeltaMPA <10% over the first 24 h, fast response as DeltaMPA > or =10% at 1 h or before loading (the others being slow responders), and high post-treatment platelet reactivity as MPA > or =56.56% (fourth quartile). Inflammatory markers (PAC-1 and P-selectin) and vasodilator-stimulated phosphoprotein (VASP) were also evaluated according to onset of action.


RESULTS
Fifty-five percent of patients were slow responders. Noncurrent smoking and body mass index > or =25 kg/m(2) were associated with slower and lower responses. High post-treatment platelet reactivity was more frequent in slow responders (28% vs. 14%, p < 0.0001). There was a clopidogrel dose-effect relationship on DeltaMPA, with a trend toward faster onset of platelet inhibition in the 900-mg loading dose group. Slow responders had a slower and lower decrease in PAC-1 and P-selectin and higher VASP index at 6 h (76.5% vs. 66.4%, p = 0.019) and 24 h (70.3% vs. 61.5%, p = 0.049).


CONCLUSIONS
Slow response to clopidogrel, within the first hour of administration, is a reliable marker of low response at 24 h and high post-treatment platelet reactivity.
Bellemain-Appaix
Anne
A
Assistance Publique Hôpitaux de Paris, Institut de Cardiologie, Pitié-Salpêtrière University Hospital, Paris, France.
Montalescot
Gilles
G
Silvain
Johanne
J
Barthélémy
Olivier
O
Beygui
Farzin
F
Collet
Jean-Philippe
JP
Sideris
Georges
G
Meuleman
Catherine
C
Bal-Dit-Sollier
Claire
C
Lellouche
Nicolas
N
Ducrocq
Grégory
G
Slama
Michel
M
Milleron
Olivier
O
Henry
Patrick
P
Drouet
Ludovic
L
D054058:Acute Coronary Syndrome / Q000188:drug therapy*; D000244:Adenosine Diphosphate / Q000032:analysis; D000368:Aged; D054316:Biomarkers, Pharmacological / Q000032:analysis; D000077144:Clopidogrel; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D016896:Treatment Outcome
D054316:Biomarkers, Pharmacological; D010975:Platelet Aggregation Inhibitors; D000244:Adenosine Diphosphate; D000077144:Clopidogrel; D013988:Ticlopidine