Platelet aggregation inhibition in patients receiving statins either fully or partially metabolized by CYP3A4.
Clopidogrel therapy is the standard for prevention of cardiovascular thrombotic events. Clopidogrel is converted to an active thiol by the cytochrome P450 CYP 3A4 and 2C19 enzymes. Recent studies suggest that statins metabolized by CYP3A4 attenuate the anti-aggregatory effect of clopidogrel. We evaluated the effect of CYP3A4-metabolized statins (atorvastatin, group 1) and partially-CYP3A4-metabolized statins (simvastatin, group 2) on platelet aggregation inhibition (PAI) when given concomitantly with clopidogrel as compared to patients who were statin naive (group 3). PAI was measured by PlateletWorks (Helena Laboratories ICHOR) using the platelet P2Y12 receptor agonist ADP (20 micromol). All patients were on clopidogrel therapy (75 mg/day). Non-responsiveness was defined as a PAI of < 35%. There was no statistical difference in mean PAI among groups; a higher prevalence of clopidogrel non-responders was noted in group 1 compared to group 3 (p=0.002). Multivariate analysis, adjusting for unequal presence of metabolic syndrome and hypertension, we found no statistical difference between groups. Our data suggests that statins, either fully or partially metabolized by CYP3A4, do not influence PAI when clopidogrel is used at 75 mg/day, even after adjusting for risk factors. We concluded that concomitant statins with clopidogrel therapy does not influence the effect of clopidogrel in PAI.
Polena
Sotir
S
Lenox Hill Hospital, New York, NY, USA.
Gupta
Manish P
MP
Shaikh
Hafiza
H
Zazzali
Kathleen
K
Coplan
Neil
N
Gintautas
Jonas
J
Labana
Subir Singh
SS
Soffer
Daniel
D
D000368:Aged; D000924:Anticholesteremic Agents / Q000008:administration & dosage*; D000069059:Atorvastatin; D000077144:Clopidogrel; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism*; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D006538:Heptanoic Acids / Q000008:administration & dosage* / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D011758:Pyrroles / Q000008:administration & dosage* / Q000378:metabolism; D019821:Simvastatin / Q000008:administration & dosage* / Q000378:metabolism; D013927:Thrombosis / Q000517:prevention & control; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology
D000924:Anticholesteremic Agents; D006538:Heptanoic Acids; D010975:Platelet Aggregation Inhibitors; D011758:Pyrroles; D000069059:Atorvastatin; D000077144:Clopidogrel; D019821:Simvastatin; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D013988:Ticlopidine