Einfluss von Statinen auf die antithrombozytäre Wirkung von Clopidogrel nach Stentimplantation

Zusammenfassung

Hintergrund und Fragestellung: Aufgrund umfangreicher klinischer Daten stellen Statine kombiniert mit Clopidogrel eine wesentliche Stütze in der Prophylaxe und Behandlung kardialer ischämischer Ereignisse dar. Durch experimentelle und klinische Untersuchungen wurde die Hypothese aufgestellt, dass vor allem das über Cytochrom P450 3A4 (CYP3A4) verstoffwechselte Atorvastatin den antithrombozytären Effekt von Clopidogrel hemmt.

Patienten und Methodik: Wir untersuchten bei 319 Patienten mit koronarer Stentimplantation den Einfluss verschiedener Statine auf die Thrombozytenaggregationshemmung mittels Lichttransmissionsaggregometrie > 6 h nach Einnahme einer Initialdosis von 600 mg Clopidogrel. 253 Patienten waren mit einer Statin-Therapie vorbehandelt (Atorvastatin, Fluvastatin oder Simvastatin), 66 Patienten erhielten kein Statin. In einer 3-monatigen Nachbeobachtungsphase wurden kardiovaskuläre Ereignisse bei den unterschiedlichen Patientengruppen erfasst.

Ergebnisse: Weder innerhalb der Statin-Subgruppen noch zwischen Patienten mit und ohne Statinbehandlung bestand eine signifikante Differenz in der Thrombozytenfunktion. Auch die Häufigkeit kardiovaskulärer Ereignisse nach 3 Monaten unterschied sich zwischen den Patientengruppen nicht signifikant.

Folgerung: Für unser Patientenkollektiv können wir eine „Ex-vivo-Statin-Clopidogrel-Interaktion” und eine prognostische Relevanz nach 3 Monaten ausschließen. Der vorher beschriebene hemmende Effekt CYP3A4-abhängiger Statine auf die antithrombozytäre Wirkung von Clopidogrel scheint bei der hohen Aufsättigungsdosis von 600 mg Clopidogrel in unserem Patientenkollektiv nicht relevant zu sein.

Summary

Background and objective: Statins are frequently given in conjunction with clopidogrel for prophylaxis and therapy of coronary heart disease. The antiplatelet effect of clopidogrel may be attenuated by lipophilic statins such as atorvastatin. It was the aim of this study to measure the antiplatelet effect of clopidogrel and the incidence of cardiovascular events after stent implantation in patients with coronary artery stenting.

Patients and methods: ADP-induced aggregometry was used in 319 patients after coronary artery stent implantation to determine whether added administration of clinically relevant statins would affect the antiplatelet action of clopidogrel. Also a three-month follow-up was undertaken to determine the incidence of cardiovascular events.

Results: There were no significant differences between the statin-receiving subgroups, either in platelet aggregation nor in clinical outcome in our cohort.

Conclusion: No statin-clopidogrel interaction nor any clinically relevant events were documented in the studied cohort. No interaction between CYP3A4 statins and a single loading dose of 600 mg clopidogrel was documented in this cohort.

Schlüsselwörter

Clopidogrel - Statine - Interaktion - Cytochrom P450 3A4

Key words

clopidogrel - statins - interaction - cytochrome P450 3A4

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