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Medientyp:
E-Artikel
Titel:
Interaction of clopidogrel and statins in secondary prevention after cerebral ischaemia – a randomized, double‐blind, double‐dummy crossover study
Beschreibung:
<jats:sec><jats:title>Aims</jats:title><jats:p>Variability in responsiveness to clopidogrel is a clinical problem in secondary prevention after cerebral ischaemia which has been suggested to be linked to competitive metabolization of clopidogrel and cytochrome <jats:styled-content style="fixed-case">P450</jats:styled-content> (<jats:styled-content style="fixed-case">CYP</jats:styled-content>) <jats:styled-content style="fixed-case">3A4</jats:styled-content>‐oxidated statins such as simvastatin. We assessed the hypothesis that simvastatin, in contrast to <jats:styled-content style="fixed-case">CYP 2C9</jats:styled-content>‐metabolized fluvastatin, reduces clopidogrel‐mediated platelet inhibition.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We performed a randomized, double‐blind, double‐dummy, two period crossover study in 13 patients with cerebral ischaemia (8F, 5 M), aged 64.1 ± 8.0 years (mean ± <jats:styled-content style="fixed-case">SD</jats:styled-content>). After a 14 day period in which all patients received 75 mg clopidogrel day<jats:sup>−1</jats:sup>, patients additionally received either 20 mg simvastatin day<jats:sup>−1</jats:sup> or 80 mg fluvastatin day<jats:sup>−1</jats:sup> for 14 days. Regimens were crossed over after a 14 day wash‐out period and switched regimens were continued for another 14 days. Platelet aggregation, clopidogrel active metabolite (<jats:styled-content style="fixed-case">CAM</jats:styled-content>) plasma concentrations and routine laboratory parameters including prothrombin time (<jats:styled-content style="fixed-case">PT</jats:styled-content>) Quick percent value were assessed at baseline and following each treatment phase.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Clopidogrel reduced platelet aggregation in all patients as expected. Platelet aggregation and <jats:styled-content style="fixed-case">CAM</jats:styled-content> plasma concentrations were unaltered when simvastatin or fluvastatin was added to clopidogrel. Simvastatin decreased <jats:styled-content style="fixed-case">PT</jats:styled-content> Quick percent value (decrease from 109 ± 10.5% to 103 ± 11%, <jats:italic>P</jats:italic> < 0.05) when combined with clopidogrel but there was no such change following treatment with fluvastatin and clopidogrel.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>Our data indicate that treatment with <jats:styled-content style="fixed-case">CYP 3A4</jats:styled-content>‐metabolized simvastatin does not jeopardize clopidogrel‐mediated inhibition of platelet aggregation. After co‐administration of simvastatin and clopidogrel we observed a decrease in the <jats:styled-content style="fixed-case">PT</jats:styled-content> Quick percent value which could be due to simvastatin‐induced reduction of activity of prothrombin fragment 1 + 2.</jats:p></jats:sec>