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Current understanding of coronary in-stent restenosis

Pathophysiology, clinical presentation, diagnostic work-up, and management

Konzepte zur Pathophysiologie, Klinik, Diagnostik und Therapie der Instent-Restenose

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Zusammenfassung

Die medizinische Effektivität einer koronaren Stentimplantation wird durch die Instent-Restenose entscheidend eingeschränkt. Sie geht mit einer relevanten Morbidität und erheblichen Kosten einher. Jährlich müssen weltweit etwa 250 000 Patienten wegen einer koronaren In-stent-Restenose behandelt werden. Die Pathophysiologie des Instent-Rezidives ist vielfältig und umfasst Entzündungsprozesse, die Migration und Proliferation von glatten Muskelzellen und die Akkumulation von extrazellulärer Matrix. Diese Vorgänge unterliegen verschiedenen molekularen Steuerungsmechanismen. Trotz der vordergründig benigen Natur der Instent-Restenose erwies sich die Behandlung als sehr problematisch. Ungeachtet der Art der bisher verwendeten kathetergestützen und systemischen Therapiestrategien mussten erneute Restenoseraten von im Mittel 50% in Kauf genommen werden. Erst durch eine zusätzliche intrakoronare Bestrahlung der zuvor dilatierten Instent-Restenose ließ sich in mehreren randomisierten Studien eine Senkung der erneuten Rezidivhäufigkeit um etwa 50% zeigen. Erste Studien zum Einsatz von medikamenten-freisetzenden Stents bei der Instent-Restenose haben zu äußerst vielversprechenden Ergebnissen geführt, weswegen sich diese Therapieform zur Behandlung der Instent-Restenose möglicherweise zukünftig durchsetzen wird. Dieser Übersichtartikel stellt die wesentlichen histopathologischen und molekularbiologischen Befunde zur Pathophysiologie, die Epidemiologie, Prädiktoren und diagnostische Strategien für die Instent-Restenose zusammen und erläutert den Wert der zur Verfügung stehenden systemischen und kathetergestützen Therapieoptionen detailliert.

Summary

In-stent restenosis is the limiting entity following coronary stent implantation. It is associated with significant morbidity and cost and thus represents a major clinical and economical problem. Worldwide, approximately 250 000 in-stent restenotic lesions per year have to be dealt with. The pathophysiology of instent restenosis is multifactorial and comprises inflammation, smooth muscle cell migration and proliferation and extracellular matrix formation, all mediated by distinct molecular pathways. Instent restenosis has been recognised as very difficult to manage, with a repeat restenosis rate of 50% regardless of the mechanical angioplasty device used. Much more favourable results were reported for the adjunctive irradiation of the in-stent restenotic lesion, with a consistent reduction of the incidence of repeat in-stent restenosis by 50%. Data from the first clinical trials on drug-eluting stents for the treatment of in-stent restenosis have shown very much promise yielding this strategy likely to become the treatment of choice. This review outlines the histological and molecular findings of the pathophysiology, the epidemiology, the predictors and the diagnostic work-up of in-stent restenosis and puts emphasis on the various treatment options for its prevention and therapy.

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  1. Kardiologie, Klinikum der Ludwig-Maximilians-Universität München—Innenstadt, Ziemssenstraße 1, 80336, München, Germany

    T. M. Schiele F.E.S.C., F.S.C.A.I.

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Correspondence to T. M. Schiele F.E.S.C., F.S.C.A.I..

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This review article is dedicated to Professor Karl Theisen, a noble mentor and outstanding personality, with gratitude.

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Schiele, T.M. Current understanding of coronary in-stent restenosis. ZS Kardiologie 94, 772–790 (2005). https://doi.org/10.1007/s00392-005-0299-x

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