The antiplatelet effect of clopidogrel is not attenuated by statin treatment in stable patients with ischemic heart disease

Pernille Vinholt; Tina Svenstrup Poulsen; Lars Korsholm; Søren Risom Kristensen; Jesper Hallas; Per Damkier; Hans Mickley

doi:10.1160/TH05-01-0046

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2005; 94(02): 438-443
DOI: 10.1160/TH05-01-0046

Cell Signalling and Vessel Remodelling

Schattauer GmbH

The antiplatelet effect of clopidogrel is not attenuated by statin treatment in stable patients with ischemic heart disease

Pernille Vinholt

¹Department of Cardiology, Odense University Hospita

,

Tina Svenstrup Poulsen

¹Department of Cardiology, Odense University Hospita

,

Lars Korsholm

²Department of Statistics, University of Southern Denmark

,

Søren Risom Kristensen

³Department KKA, Clinical Chemistry, Odense University Hospital

,

Jesper Hallas

⁴Department of Internal Medicine, Odense University Hospital

,

Per Damkier

⁵Department KKA, Clinical Pharmacology, Odense University Hospital, Odense, Denmark

,

Hans Mickley

¹Department of Cardiology, Odense University Hospita

› Institutsangaben

Abstract

Summary

Recent studies suggest that cytochrome P450 (CYP) 3A4 metabolized statins attenuate the antiaggregatory effect of clopidogrel. We evaluated how CYP3A4 metabolized statins and non- CYP3A4 metabolized statins influence platelet aggregation when given concomitantly with clopidogrel. Sixty-six stable patients with ischemic heart disease were included in this parallel group study. All patients were on clopidogrel and aspirin. Thirty-three patients received a CYP3A4 metabolized statin (simvastatin or atorvastatin), and 33 were treated with a non- CYP3A4 metabolized statin (pravastatin). The antiplatelet effect of clopidogrel was assessed at inclusion and 21 days after statin discontinuation. Platelet function was evaluated by two methods 1) optical platelet aggregometry after stimulation with 20 and 30 μM ADP, and 2 and 4 mg/l collagen, respectively, 2) a Platelet FunctionAnalyzer-100. The primary effect measure was final platelet aggregation after stimulation with 20 μM ADP. No difference was observed between patients treated with a CYP3A4 metabolized statin and patients receiving a non-CYP3A4 metabolized statin (30% point (7–42) versus 20% point (9–32), p=0.83). Platelet aggregation was not improved by discontinuation of statins for 21 days. Indeed, we found that statin treatment given concomitantly with clopidogrel resulted in an improved platelet inhibition when compared to clopidogrel given alone. The antiplatelet effect of clopidogrel is not attenuated by concomitant treatment with a CYP3A4 metabolized statin in patients with clinical stable ischemic heart disease.

Keywords

Ischemic heart disease - lipid mediators - platelet pharmacology

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Referenzen

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