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Eur Heart J ; 29(13): 1635-43, 2008 Jul.
Article in English | MEDLINE | ID: mdl-18503057

ABSTRACT

AIMS: There are growing data suggesting a clinical relevance of residual platelet aggregation (RPA) in patients undergoing PCI. Drug-drug interaction of statins and clopidogrel has been controversially discussed in ex vivo studies and clinical trials. The aim of the present study was to investigate the effects of peri-procedural statin medication on the metabolization of aspirin and clopidogrel with regard to platelet aggregation and clinical outcome in patients undergoing coronary intervention. METHODS AND RESULTS: Patients with coronary stenting for symptomatic coronary artery disease are routinely evaluated by platelet function analysis in a monocentre registry, and for the present study, a consecutive cohort of 1155 patients were analysed. About 87.7% of the patients were treated with statins at the time of platelet function analysis. Residual platelet activity assessed by adenosine diphosphate (20 micromol/L)-induced platelet aggregation was not significantly influenced by statin treatment. Nor the significant effects of CYP3A4-metabolization pathway on post-treatment aggregation were recorded, although there was even a trend to lower RPA values in patients treated with CYP3A4-metabolized statins. Further, in an inter-individual analysis comparing patients treated with CYP3A4- and non-CYP3A4-metabolized statins, no time-dependent difference of clopidogrels anti-aggregatory effects was observed. Clinical follow-up of major adverse events (myocardial infarction, ischaemic stroke, death) in 991 patients within 3 months revealed no significant adverse effects of statin treatment on clinical outcome. Instead, statin treatment was independently associated with lower incidence of composite events (HR 0.44, 95% confidence interval 0.23-0.83, P = 0.01). CONCLUSION: Peri-procedural co-administration of statins does not increase the post-interventional RPA in cardiovascular patients treated with dual antiplatelet therapy and does not worsen the clinical prognosis of these patients.


Subject(s)
Aspirin/administration & dosage , Coronary Stenosis/therapy , Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage , Platelet Aggregation Inhibitors/administration & dosage , Platelet Aggregation/drug effects , Ticlopidine/analogs & derivatives , Adult , Aged , Aged, 80 and over , Aspirin/pharmacology , Clopidogrel , Cytochrome P-450 CYP3A/metabolism , Drug Interactions , Drug Therapy, Combination , Female , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Male , Middle Aged , Platelet Aggregation Inhibitors/pharmacology , Prognosis , Stents , Ticlopidine/administration & dosage , Ticlopidine/pharmacology
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