CLINICAL RESEARCH: INTERVENTIONAL CARDIOLOGY
Addition of paclitaxel to contrast media prevents restenosis after coronary stent implantation
Bruno Scheller, MD*,*,
Ulrich Speck, PhD ,
Alexander Schmitt*,
Michael Böhm, MD* and
Georg Nickenig, MD*
* Internal Medicine III (Cardiology/Angiology), University of Saarland, Homburg/Saar, Germany
Department of Radiology, Humboldt University, Charité, Berlin, Germany
Manuscript received March 10, 2003;
revised manuscript received June 5, 2003,
accepted June 9, 2003.
* Reprint requests and correspondence: Dr. Bruno Scheller, University of Saarland, Internal Medicine III, D 66421 Homburg/Saar, Germany.
bruno.scheller{at}uniklinik-saarland.de
OBJECTIVES: The present study was designed to test the efficacy of paclitaxel added to the contrast agent iopromide in the prevention of restenosis.
BACKGROUND: Contrast media adhere to the coronary vessel wall for some seconds after injection. Such a layer of contrast agent could serve as a matrix for antiproliferative drugs.
METHODS: Thirty-four stents were implanted into the left anterior descending and circumflex coronary arteries of 17 pigs, using a 1.2:1.0 overstretch ratio. The unsupplemented contrast agent iopromide-370 was used as a control; the treatment groups were treated with 80 ml intracoronary iopromide plus either 100 or 200 µmol/l paclitaxel, or 80 ml intravenous iopromide plus 200 µmol/l paclitaxel. Quantitative angiography and histomorphometry were used to assess comparable baseline parameters between the treatment groups.
RESULTS: A short time incubation (3 min) almost completely inhibited vascular smooth muscle cell proliferation, sustained for up to 12 days. Whereas intravenous paclitaxel had no effect, intracoronary application of paclitaxel reduced the diameter stenosis from 55 ± 13% to 29 ± 18% and 13 ± 12%. Late lumen loss dropped from 1.94 ± 0.35 mm under the control condition to 1.19 ± 0.55 mm with 100 µmol/l paclitaxel and to 0.82 ± 0.54 mm with 200 µmol/l paclitaxel. Histomorphometry revealed a corresponding dose-dependent reduction of the neointimal area and restenosis by intracoronary iopromide paclitaxel. Assessment of left ventricular function and myocardial histology revealed no adverse effects of intracoronary paclitaxel application.
CONCLUSIONS: This study provides evidence that intracoronary application of a taxane dissolved in a contrast medium profoundly inhibits in-stent restenosis. This novel, widely feasible approach may be suited for the prevention of restenosis in a broad spectrum of interventional treatment regimens.
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Abbreviations and Acronyms
| | CM | = contrast medium | | Cx | = circumflex artery | | DES | = drug-eluting stent | | DMEM | = Dulbecco's minimal essential medium | | EEL | = external elastic lamina | | FBS | = fetal bovine serum | | LAD | = left anterior descending coronary artery |
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