title: Statins do not adversely affect post-interventional residual platelet aggregation and outcomes in patients undergoing coronary stenting treated by dual antiplatelet therapy.
abstract: OBJECTIVE
  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.
  
  
  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 clopidogreĺs 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Medizinische Klinik III, University Hospital Tübingen, Otfried-Müller-Strasse 10 72076, Tübingen, Germany. tobias.geisler@med.uni-tuebingen.de
authors.forename: Tobias
authors.initials: T
authors.lastname: Geisler
authors.forename: Christine
authors.initials: C
authors.lastname: Zürn
authors.forename: Maria
authors.initials: M
authors.lastname: Paterok
authors.forename: Katrin
authors.initials: K
authors.lastname: Göhring-Frischholz
authors.forename: Boris
authors.initials: B
authors.lastname: Bigalke
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Stellos
authors.forename: Peter
authors.initials: P
authors.lastname: Seizer
authors.forename: Bjoern F
authors.initials: BF
authors.lastname: Kraemer
authors.forename: Jürgen
authors.initials: J
authors.lastname: Dippon
authors.forename: Andreas E
authors.initials: AE
authors.lastname: May
authors.forename: Christian
authors.initials: C
authors.lastname: Herdeg
authors.forename: Meinrad
authors.initials: M
authors.lastname: Gawaz
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001241:Aspirin / Q000008:administration & dosage* / Q000494:pharmacology; D000077144:Clopidogrel; D023921:Coronary Stenosis / Q000628:therapy*; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology; D011379:Prognosis; D015607:Stents; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D013988:Ticlopidine; D001241:Aspirin