Effect of atorvastatin and pravastatin on platelet inhibition by aspirin and clopidogrel treatment in patients with coronary stent thrombosis.
We sought to determine a potential interaction between statins and antiplatelet therapy with aspirin and clopidogrel. Previous laboratory studies have shown a possible drug-drug interaction of statins metabolized by cytochrome P450 3A4 and clopidogrel (prodrug metabolized by cytochrome P450 3A4), resulting in an impaired inhibitory effect of clopidogrel on platelet aggregation. However, conclusive prospective data assessing this potentially relevant interaction are lacking. In 73 patients, 23 with previous coronary stent thrombosis (ST) (ST group) and 50 without coronary ST (control group), platelet aggregation was measured 3 times in monthly intervals using light transmission aggregometry (adenosine diphosphate [ADP] and arachidonic acid induction). Measurements were carried out with aspirin monotherapy (100 mg/day), dual antiplatelet therapy with aspirin plus clopidogrel (75 mg/day), and additional treatment of 20 mg/day of atorvastatin or 40 mg/day of pravastatin. ADP (5 and 20 micromol)-induced platelet aggregation was significantly decreased with clopidogrel (p <0.001) but remained stable under additional treatment with atorvastatin or pravastatin in the 2 groups. Patients with previous ST showed a higher ADP-induced aggregation level than control subjects. This difference was not influenced by clopidogrel or statin treatment. In conclusion, patients with previous ST show a higher aggregation level than control subjects independent of statin treatment. Atorvastatin and pravastatin do not interfere with the antiaggregatory effect of aspirin and clopidogrel. In conclusion, drug-drug interaction between dual antiplatelet therapy and atorvastatin or pravastatin seems not to be associated with ST.
Wenaweser
Peter
P
Department of Cardiology, University Hospital, Bern, Switzerland. peter.wenaweser@insel.ch
Windecker
Stephan
S
Billinger
Michael
M
Cook
Stephane
S
Togni
Mario
M
Meier
Bernhard
B
Haeberli
Andre
A
Hess
Otto M
OM
D000368:Aged; D001241:Aspirin / Q000009:adverse effects*; D000069059:Atorvastatin; D000077144:Clopidogrel; D023903:Coronary Restenosis / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy*; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D004562:Electrocardiography; D005260:Female; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects; D017035:Pravastatin / Q000627:therapeutic use*; D011446:Prospective Studies; D011475:Prosthesis Failure; D011758:Pyrroles / Q000627:therapeutic use*; D015607:Stents; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives*; D016896:Treatment Outcome
D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010975:Platelet Aggregation Inhibitors; D011758:Pyrroles; D000069059:Atorvastatin; D000077144:Clopidogrel; D017035:Pravastatin; D013988:Ticlopidine; D001241:Aspirin