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(Circulation. 2002;106:2649.)
© 2002 American Heart Association, Inc.

Brief Rapid Communications

Mechanism of Late In-Stent Restenosis After Implantation of a Paclitaxel Derivate–Eluting Polymer Stent System in Humans

Renu Virmani, MD; Francesco Liistro, MD; Goran Stankovic, MD; Carlo Di Mario, MD, PhD; Matteo Montorfano, MD; Andrew Farb, MD; Frank D. Kolodgie, PhD; Antonio Colombo, MD

From the Catheterization Laboratories, Ospedale San Raffaele and Emo Centro Cuore Columbus, Milan, Italy (F.L., G.S., C.D.M., M.M., A.C.), and the Department of Cardiovascular Pathology (R.V., A.F., F.D.K.), Armed Forces Institute of Pathology, Washington, DC.

Correspondence to Renu Virmani, MD, Department of Cardiovascular Pathology, Armed Forces Institute of Pathology 6825, 16th St NW, Washington, DC 20306-6000. E-mail virmani{at}afip.osd.mil

Background— We recently reported delayed angiographic restenosis in 15 patients who received 7-hexanoyltaxol (QP2)–eluting polymer stents (QuaDS) for the treatment of in-stent restenosis. This study presents the histological findings of atherectomy specimens from a subset of these patients receiving implants.

Methods and Results— Between October and December 2001, 5 patients treated with QuaDS-QP2 stents underwent directional coronary atherectomy at 11.2±1.0 months for recurrent in-stent restenosis. Restenotic lesion composition was assessed with special stains, immunohistochemistry with quantitative image analysis, and, in one specimen, transmission electron microscopy. Atherectomy specimens contained fibrin interspersed in a smooth muscle cell–rich neointima with proteoglycan matrix. In 2 of 5 specimens, large aggregates of macrophages and T-lymphocytes were noted. These areas of active inflammation demonstrated a relatively high proliferation index by Ki-67 antibody staining, whereas the proliferation index in smooth muscle cell–rich restenotic areas was low.

Conclusion— Restenotic lesions from QuaDS-QP2–eluting stents at 12 months show persistent fibrin deposition with varying degrees of inflammation. These pathological changes, representing delayed healing, are usually observed up to only 3 months in human coronary arteries with stainless steel balloon-expandable stents. The nonreabsorbable polymer alone may have induced chronic inflammation.

Key Words: fibrin • inflammation • stents • restenosis

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