Drug-Coated Balloons for Restenosis Prophylaxis

Abstract

Drug-coated balloons for restenosis prophylaxis provide a high local drug concentration with minimal or no systemic adverse effects. Their development was both delayed and facilitated by the introduction of drug-eluting stents: delayed because sustained release kinetics from stent platforms seemed to be essential and facilitated because prior experience with stents allowed selection of testing methods and drugs. Currently, a variety of drug-coated balloons are available, basically consisting of a coating containing paclitaxel at a dose of about 3 µg/mm² balloon surface, and different additives influencing the adherence and release of the drug, e. g., contrast agent, urea, or various amphiphilic compounds. The drug is almost completely released during a single inflation of 30 – 60 seconds. Studies in animals and several independent randomized clinical trials in coronary and peripheral arteries demonstrate effective reduction of neointimal proliferation, restenosis, and revascularization persisting for at least 2 years or 5 years according to one study in coronary arteries. Drug-coated balloons are preferably used for treating coronary in-stent restenosis and de novo and restenotic lesions in peripheral vessels. No coating-related adverse events have been observed in clinical trials. Persistent efficacy may be explained by the long residence time of paclitaxel in tissue or inhibition of an essential first step in the chain of events leading to neointimal proliferation.

Citation Format:

• Speck U., Scheller B., Hamm B. Drug-Coated Balloons for Restenosis Prophylaxis. Fortschr Röntgenstr 2014; 186: 348 – 358

Zusammenfassung

Arzneimittel-beschichtete Ballons bewirken eine hohe lokale Arzneistoffkonzentration bei minimalen oder fehlenden systemischen Nebenwirkungen. Durch die Einführung der Arzneimittel-freisetzenden Stents war ihre Entwicklung einerseits verzögert andererseits befördert: Verzögert weil die lange Zeit anhaltende Freisetzung von einer Stent-Plattform als essentiell angesehen wurde und erleichtert weil die bereits existierende Erfahrung mit den Stents bei der Wahl der Prüfmetho-den und Arzneistoffe eine Hilfe war. Derzeit sind mehrere unterschiedliche arzneimittelbeschichtete Ballonkatheter verfügbar, die grundsätzlich eine Schicht mit ca. 3 µg/mm² Paclitaxel auf der Ballonoberfläche tragen sowie unterschiedliche Zusätze, die die Haftung und Freisetzung des Wirkstoffs beeinflussen, z. B. ein Kontrastmittel, Harnstoff oder verschiedene amphiphile Substanzen. Der Arzneistoff wird während einer einzelnen Inflation von 30 – 60 sec weitgehend vollständig freigesetzt. Tierexperimentelle Untersuchungen und mehrere unabhängige randomisierte klinische Studien an koronaren und peripheren Arterien zeigen eine wirksame Verminderung der Neointimaproliferation, Restenose und Revaskularisierung, ein Effekt, der für mindestens 2, nach einer Studie an Koronarien auch 5 Jahre anhält. Die Einsatzgebiete der arzneimittelbeschichteten Ballone sind vor allem die koronare in-Stent-Restenose sowie de novo und restenotische Läsionen in peripheren Arterien. In klinischen Prüfungen wurden keine der Beschichtung zuzuordnenden unerwünschten Ereignisse registriert. Die anhaltende Wirkung kann durch die lange Verweilzeit von Paclitaxel im Gewebe erklärt werden oder durch die Hemmung eines essentiellen ersten Schrittes in einer Kette von Ereignissen, die zur Neointimaproliferation führen.

Key words

drug-coated balloon catheter - restenosis - peripheral arteries - paclitaxel - angioplasty - drug-coated balloon

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