Addition of paclitaxel to contrast media prevents restenosis after coronary stent implantation.

Abstract

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 mumol/l paclitaxel, or 80 ml intravenous iopromide plus 200 mumol/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 mumol/l paclitaxel and to 0.82 +/- 0.54 mm with 200 mumol/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.

• Authors: Bruno Scheller, Ulrich Speck, Alexander Schmitt, Michael Böhm, Georg Nickenig
• Journal: Journal of the American College of Cardiology (J Am Coll Cardiol) Vol. 42 Issue 8 Pg. 1415-20 (Oct 15 2003) ISSN: 0735-1097 [Print] United States
• PMID: 14563585 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Phytogenic
• Contrast Media
• Iohexol
• iopromide
• Paclitaxel

Topics

• Animals
• Antineoplastic Agents, Phytogenic (administration & dosage)
• Cells, Cultured
• Contrast Media
• Coronary Restenosis (prevention & control)
• Coronary Vessels (drug effects)
• In Vitro Techniques
• Iohexol (administration & dosage, analogs & derivatives)
• Paclitaxel (administration & dosage)
• Stents
• Swine