European Heart Journal Advance Access originally published online on May 24, 2008
European Heart Journal 2008 29(13):1635-1643; doi:10.1093/eurheartj/ehn212
Statins do not adversely affect post-interventional residual platelet aggregation and outcomes in patients undergoing coronary stenting treated by dual antiplatelet therapy
1 Medizinische Klinik III, University Hospital Tübingen, Otfried-Müller-Strasse 10 72076, Tübingen, Germany
2 Department of Mathematics, University of Stuttgart, Stuttgart, Germany
Received 4 July 2007; revised 17 April 2008; accepted 6 May 2008; online publish-ahead-of-print 24 May 2008.
* Corresponding author. Tel: +49 7071 2983688, Fax: +49 7071 295749, Email: tobias.geisler{at}med.uni-tuebingen.de
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 µmol/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 clopidogre
s 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.
Key Words: Stents • Interactions • Clopidogrel • Statins • CYP3A4 • Platelets