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J Am Coll Cardiol, 2002; 39:183-193
© 2002 by the American College of Cardiology Foundation
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REVIEW ARTICLE

Coronary in-stent restenosis: Current status and future strategies

Harry C. Lowe, FRACP, PhD*{dagger}, Stephen N. Oesterle, MD, FACC* and Levon M. Khachigian, PhD{dagger},*

* Cardiology Division, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
{dagger} The Centre for Thrombosis and Vascular Research, University of New South Wales, Sydney, Australia

Manuscript received July 11, 2001; revised manuscript received October 4, 2001, accepted October 26, 2001.

* Reprint requests and correspondence: Associate Professor Levon M. Khachigian, Centre for Thrombosis and Vascular Research, School of Pathology, University of New South Wales, Sydney NSW 2052, Australia.
L.Khachigian{at}unsw.edu.au

In-stent restenosis (ISR) is a novel pathobiologic process, histologically distinct from restenosis after balloon angioplasty and comprised largely of neointima formation. As percutaneous coronary intervention increasingly involves the use of stents, ISR is also becoming correspondingly more frequent. In this review, we examine the available studies of the histology and pathogenesis of ISR, with particular reference to porcine and other animal models. An overview of mechanical treatments is then provided, which includes PTCA, directional coronary atherectomy and high speed rotational atherectomy. Radiation-based therapies are discussed, including a summary of current problems associated with this modality of treatment. Finally, novel strategies for the prevention of ISR are addressed, including novel developments in stents and stent coatings, conventional drugs, nucleic acid-based drugs and gene transfer. Until recently, limited pharmacologic and mechanical treatment options have been available for both treatment and prevention of ISR. However, recent advances in gene modification and gene transfer therapies and, more particularly, in local stent-based drug delivery systems make it conceivable that the incidence of ISR will now be seriously challenged.

Abbreviations and Acronyms
  ARTIST
  Angioplasty Versus Rotational Atherectomy for Treatment of In-Stent Restenosis trial
  AS
  antisense
  DCA
  directional coronary atherectomy
  DNA
  deoxyribonucleic acid
  DZ
  deoxyribonucleic acid enzyme
  HSRA
  high-speed rotational atherectomy
  Ir
  iridium
  ISR
  in-stent restenosis
  NI
  neointima
  P
  phosphorus
  PRESTO
  Prevention of Restenosis with Tranilast and its Outcomes trial
  PREVENT
  Proliferation Reduction with Vascular Energy Trial
  PTCA
  percutaneous transluminal coronary angioplasty
  RAVEL
  Rapamycin-eluting versus Plain Polymer Stents trial
  RNA
  ribonucleic acid
  ROSTER
  Randomized Trial of Rotational Atherectomy versus Balloon Angioplasty for In-Stent Restenosis
  RZ
  ribozyme
  SCRIPPS
  Scripps Coronary Radiation to Inhibit Proliferation Post Stenting trial
  SMC
  smooth muscle cell
  Sr-90
  strontium90
  START
  Stents And Radiation Therapy Trial
  WRIST
  Washington Radiation for In-Stent Restenosis Trial




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