ADP induced platelet degranulation in healthy individuals is reduced by clopidogrel after pretreatment with atorvastatin

Michael Piorkowski; Ulf Weikert; Peter-Lothar Schwimmbeck; Peter Martus; Heinz-Peter Schultheiss; Ursula Rauch

doi:10.1160/TH03-12-0738

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2004; 92(03): 614-620
DOI: 10.1160/TH03-12-0738

Platelets and Blood Cells

Schattauer GmbH

ADP induced platelet degranulation in healthy individuals is reduced by clopidogrel after pretreatment with atorvastatin

Michael Piorkowski

¹Department of Internal Medicine / Cardiology, Institute for Medical Informatics, Biometry and Epidemiology, Campus Benjamin Franklin, Charité - Universitätsmedizin Berlin, Berlin, Germany

,

Ulf Weikert

¹Department of Internal Medicine / Cardiology, Institute for Medical Informatics, Biometry and Epidemiology, Campus Benjamin Franklin, Charité - Universitätsmedizin Berlin, Berlin, Germany

,

Peter-Lothar Schwimmbeck

¹Department of Internal Medicine / Cardiology, Institute for Medical Informatics, Biometry and Epidemiology, Campus Benjamin Franklin, Charité - Universitätsmedizin Berlin, Berlin, Germany

,

Peter Martus

¹Department of Internal Medicine / Cardiology, Institute for Medical Informatics, Biometry and Epidemiology, Campus Benjamin Franklin, Charité - Universitätsmedizin Berlin, Berlin, Germany

,

Heinz-Peter Schultheiss

¹Department of Internal Medicine / Cardiology, Institute for Medical Informatics, Biometry and Epidemiology, Campus Benjamin Franklin, Charité - Universitätsmedizin Berlin, Berlin, Germany

,

Ursula Rauch

¹Department of Internal Medicine / Cardiology, Institute for Medical Informatics, Biometry and Epidemiology, Campus Benjamin Franklin, Charité - Universitätsmedizin Berlin, Berlin, Germany

› Author Affiliations

Abstract

Summary

Statins inhibit platelet reactivity and reduce blood thrombogenicity.The effectiveness of clopidogrel in inhibiting platelet reactivity was suggested to be reduced in the presence of atorvastatin due to shared enzymes in metabolism. Healthy individuals, 17 pretreated with atorvastatin (20 mg/d for 3 days) and 17 without pretreatment, as well as 15 patients with stable coronary artery disease (CAD) and concurrent atorvastatin therapy were started on clopidogrel (loading dose 300 mg, then 75 mg/d). P-selectin on platelet surface after stimulation with ADP or Thrombin Receptor Activating Peptide (TRAP) was flow cytometrically measured before and during clopidogrel administration. Whole blood platelet agglutination was tested by a platelet function assay.TRAP and - in trend - ADP induced p-selectin exposure was reduced by the atorvastatin pretreatment before clopidogrel was added. Combining clopidogrel with atorvastatin in the healthy individuals led to a further reduction in ADP-induced platelet p-selectin exposure. Clopidogrel also reduced platelet reactivity in CAD patients with concurrent atorvastatin medication. We conclude that pretreatment with atorvastatin reduces platelet reactivity before administration of clopidgrel. No drug interaction was seen, however, platelet inhibitory effects were observed during the treatment with clopidogrel and atorvastatin.

Keywords

Platelets - hypercholesterolemia - clopidogrel - atorvastatin

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References

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