Factors that contribute to clopidogrel resistance in cardiovascular disease patients: environmental and genetic approach.
OBJECTIVE
Clopidogrel is a potent antiplatelet drug that reduces the risk of vascular events in patients with cardiovascular disease. However, several studies have shown that about a quarter of patients showed low or no response to clopidogrel therapy. In this study, factors that contribute to clopidogrel resistance were investigated in 270 cardiovascular disease patients from Jordan.


METHODS
Clopidogrel resistance was determined through platelet aggregation analysis using the Multiplate analyzer®. Genetic factors (CYP2C19*2 and PON1 Q192R) were examined using polymerase chain reaction-restriction fragment length polymorphism analysis.


RESULTS
The incidence of clopidogrel resistance among Jordanians is about 32%. Significant association between clopidogrel resistance and female gender, concomitant use of calcium channel blockers, and low HDL was found (p < 0.05). In addition, presence of CYP2C19*2 allele is strongly related to clopidogrel resistance (p < 0.001). However, lack of contribution to clipidogrel resistance was found for PON1 Q192R polymorphism, age, diabetes, hypertension, smoking and aspirin use (p > 0.05).


CONCLUSIONS
Several factors might contribute to clopidogrel resistance including gender, concomitant use of calcium channel blockers, HDL and CYP2C19*2 polymorphism.
Department of Clinical Pharmacy, Jordan University of Science and Technology, Jordan. sayerazzam@yahoo.com
Sayer I
SI
Al-Azzam
Karem H
KH
Alzoubi
Omar F
OF
Khabour
Mohammad B
MB
Nusair
Hakam
H
Al-Hadidi
Abdalla
A
Awidi
Akram
A
Saleh
D000368:Aged; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D043303:Aryldialkylphosphatase / Q000235:genetics*; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000235:genetics; D008076:Cholesterol, HDL / Q000097:blood; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19; D004351:Drug Resistance; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D020641:Polymorphism, Single Nucleotide; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use
D008076:Cholesterol, HDL; D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human; D013988:Ticlopidine