Adjusted clopidogrel loading doses according to vasodilator-stimulated phosphoprotein phosphorylation index decrease rate of major adverse cardiovascular events in patients with clopidogrel resistance: a multicenter randomized prospective study.
OBJECTIVE
This study evaluates the clinical impact of adjusting the loading dose of clopidogrel according to vasodilator-stimulated phosphoprotein (VASP) index in patients with clopidogrel resistance undergoing percutaneous coronary intervention (PCI).


BACKGROUND
Clopidogrel resistance plays a key role in ischemic recurrence after PCI. In vitro tests of clopidogrel resistance can accurately predict major adverse cardiac events after PCI.


METHODS
In this prospective, randomized, multicenter study, clopidogrel resistance was defined as a VASP index of more than 50% after a 600-mg loading dose. Patients with clopidogrel resistance undergoing coronary stenting were randomized to a control group or to the VASP-guided group, in which patients received additional bolus clopidogrel to decrease the VASP index below 50%.


RESULTS
A total of 162 patients were included. The control (n = 84) and VASP-guided groups (n = 78) had similar demographic, clinical, and biological characteristics. In the VASP-guided group, dose adjustment was efficient in 67 patients (86%) and VASP index was significantly decreased (from 69.3 +/- 10 to 37.6 +/- 13.8; p < 0.001). Eight major adverse cardiac events (5%) were recorded during the 1-month follow-up, with a significantly lower rate in the VASP-guided group compared with the control group (0% vs. 10%; p = 0.007). There was no difference in the rate of major and minor bleeding (5% vs. 4%; p = 1).


CONCLUSIONS
This is the first study to suggest that adjusting the clopidogrel loading dose according to platelet monitoring using the VASP index is safe and may significantly improve the clinical outcome after PCI in patients with clopidogrel resistance despite a first 600-mg loading dose.
Bonello
Laurent
L
Service de Cardiologie, Hôpital Universitaire Nord, Marseille, France. laurentbonello@yahoo.fr
Camoin-Jau
Laurence
L
Arques
Stéphane
S
Boyer
Christian
C
Panagides
Dimitri
D
Wittenberg
Olivier
O
Simeoni
Marie-Claude
MC
Barragan
Paul
P
Dignat-George
Françoise
F
Paganelli
Franck
F
D000368:Aged; D015906:Angioplasty, Balloon, Coronary; D002318:Cardiovascular Diseases / Q000097:blood / Q000517:prevention & control*; D015815:Cell Adhesion Molecules / Q000097:blood*; D000077144:Clopidogrel; D004351:Drug Resistance; D005260:Female; D006801:Humans; D008297:Male; D008840:Microfilament Proteins / Q000097:blood*; D009203:Myocardial Infarction / Q000097:blood / Q000188:drug therapy* / Q000628:therapy; D010750:Phosphoproteins / Q000097:blood*; D010766:Phosphorylation; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D011446:Prospective Studies; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D014664:Vasodilation / Q000187:drug effects; D000098662:Vasodilator-Stimulated Phosphoprotein
D015815:Cell Adhesion Molecules; D008840:Microfilament Proteins; D010750:Phosphoproteins; D010975:Platelet Aggregation Inhibitors; D000098662:Vasodilator-Stimulated Phosphoprotein; D000077144:Clopidogrel; D013988:Ticlopidine