Myonecrosis after elective percutaneous coronary intervention: effect of clopidogrel-statin interaction.
BACKGROUND
A recent ex vivo study suggests that the metabolic activation of clopidogrel is catalyzed by cytochrom P450 (CYP) 3A4 and is competitively inhibited by atorvastatin, but not pravastatin.


OBJECTIVE
To determine whether the incidence of procedure-related myocardial injury, assessed by cardiac troponin T (cTnT) release, is altered when clopidogrel is coadministered with a statin that is predominantly CYP3A4-metabolized.


RESULTS
Of the 211 consecutive patients who underwent coronary stenting after pretreatment with clopidogrel, 114 were receiving a CYP3A4-metabolized statin (59 simvastatin and 55 atorvastatin, Group 1), and 37 were receiving a non-CYP3A4-metabolized statin (30 pravastatin and 7 fluvastatin, Group 2) whereas 60 patients were not taking any statins (Control). All were troponin-negative before the procedure. The overall incidence of postprocedural cTnT positivity (> 0.10 ng/ml) was 30.8%. Group 2 patients were less likely to exhibit cTnT rise relative to Group 1 patients (8% versus 41.6%; p = 0.004) and relative to controls (8% versus 32.5%; p < 0.001). Multivariate analysis identified the use of a non-CYP3A4-metabolized statin before coronary stenting as the sole independent predictor for lower incidence of procedure-related cTnT elevation with estimated Odds ratios of 0.16 relative to no statin therapy (95% CI: 0.04-0.59; p = 0.006) and 0.18 relative to CYP3A4-metabolized statin therapy (95 CI: 0.053-0.637; p = 0.008)


CONCLUSIONS
Benefit derived from the preprocedural use of pravastatin and fluvastatin but not atorvastatin and simvastatin suggest that the ex vivo finding of a negative interaction when coadministering a CYP3A4-metabolized statin with clopidogrel may be of clinical significance.
Gulec
Sadi
S
Department of Cardiology, Ankara University Medical School, Ankara, Turkey.
Ozdol
Cagdas
C
Rahimov
Uzeyir
U
Atmaca
Yusuf
Y
Kumbasar
Deniz
D
Erol
Cetin
C
D000368:Aged; D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects*; D000077144:Clopidogrel; D052279:Creatine Kinase, MB Form / Q000378:metabolism; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions / Q000502:physiology; D005260:Female; D006321:Heart / Q000187:drug effects; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009203:Myocardial Infarction / Q000209:etiology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D009336:Necrosis / Q000517:prevention & control; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D012189:Retrospective Studies; D015607:Stents; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D020107:Troponin T / Q000096:biosynthesis
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010975:Platelet Aggregation Inhibitors; D020107:Troponin T; D003577:Cytochrome P-450 Enzyme System; D000077144:Clopidogrel; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D052279:Creatine Kinase, MB Form; D013988:Ticlopidine