Not all statins interfere with clopidogrel during antiplatelet therapy.
BACKGROUND
Clopidogrel and statins are frequently coadministered in patients with ischemic heart diseases. Recent reports suggested that clopidogrel's effectiveness in inhibiting adenosine diphosphate (ADP)-induced platelets aggregation is attenuated by co-administration of certain statins. The objective of the present study was to define which statin might interfere with the antiaggregation property of clopidogrel.


METHODS
We designed a pharmacokinetic study and tested ex vivo platelet function on 21 healthy volunteers who received clopidogrel and all currently commercially available statins: rosuvastatin [10 mg o.d.], simvastatin [20 mg o.d.], fluvastatin [80 mg o.d.], pravastatin [40 mg o.d.], and atorvastatin [20 mg o.d.]. Each statin was administered for 7 days followed by 1 week of wash-out period with clopidogrel treatment alone. Detection of the statins in the plasma was performed on all blood samples, using HPLC analytical method.


RESULTS
All individuals, except one, were responders to clopidogrel with inhibition of ex vivo ADP induced platelet aggregation. All statins, except pravastatin, were detectable in the plasma at the end of each treatment period in all patients, and no statin was detectable after any of the wash-out periods. Clopidogrel was significantly less efficient to prevent platelet aggregation when coadministrated with simvastatin or fluvastatin. No difference was observed in clopidogrel efficacy when coadministered with rosuvastatin, pravastatin or atorvastatin.


CONCLUSIONS
This is the first study investigating clopidogrel-statin interactions on ex vivo platelet function with all commercially available statins and which were administered to the same individuals. It demonstrates in healthy volunteers that at the doses used in this study, simvastatin and fluvastatin, but not atorvastatin, pravastatin or rosuvastatin interfere with the anti-aggregation effect of clopidogrel.
Mach
F
F
University Hospital, Geneva, Switzerland. francois.mach@medecine.unige.ch
Senouf
D
D
Fontana
P
P
Boehlen
F
F
Reber
G
G
Daali
Y
Y
de Moerloose
P
P
Sigwart
U
U
D000328:Adult; D000069059:Atorvastatin; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D000077144:Clopidogrel; D004347:Drug Interactions; D005229:Fatty Acids, Monounsaturated / Q000097:blood / Q000494:pharmacology; D005464:Fluorobenzenes / Q000097:blood / Q000494:pharmacology; D000077340:Fluvastatin; D006538:Heptanoic Acids / Q000097:blood / Q000494:pharmacology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000097:blood / Q000494:pharmacology*; D007211:Indoles / Q000097:blood / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D017035:Pravastatin / Q000097:blood / Q000494:pharmacology; D011743:Pyrimidines / Q000097:blood / Q000494:pharmacology; D011758:Pyrroles / Q000097:blood / Q000494:pharmacology; D000068718:Rosuvastatin Calcium; D019821:Simvastatin / Q000097:blood / Q000494:pharmacology; D013449:Sulfonamides / Q000097:blood / Q000494:pharmacology; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000494:pharmacology
D005229:Fatty Acids, Monounsaturated; D005464:Fluorobenzenes; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D010975:Platelet Aggregation Inhibitors; D011743:Pyrimidines; D011758:Pyrroles; D013449:Sulfonamides; D000077340:Fluvastatin; D000068718:Rosuvastatin Calcium; D000069059:Atorvastatin; D000077144:Clopidogrel; D019821:Simvastatin; D017035:Pravastatin; D013988:Ticlopidine