Antiproliferative coatings for the treatment of coronary heart disease:. what are the targets and which are the tools?
Since the advent of percutaneous coronary intervention (PCI) for stenosing coronary disease, restenosis has remained a clinical problem. Despite the emergence and evolution of coronary stents, the rate of restenosis following PCI is still 10-20%, and above 50% in high risk subgroups. With increased understanding of the pathophysiology of this process, a number of potential therapeutic targets have been identified, allowing the development of novel therapies against restenosis, which can now be delivered locally using stent platforms. Some of the reported clinical trial data utilizing drug-eluting stents (DES) have produced such profound reductions in clinical and angiographic restenosis that we have been tempted to believe we are on the brink of eradicating this process completely. As the initial excitement subsides, however, there is a need to decide whether these tools will remain effective in real-world interventional practice. In this article we review the pathophysiology of the restenotic process, and the biological targets of the DES therapies currently available in clinical practice. We attempt to define clinical target populations for DES therapy, and assess the impact on outcomes thus far. We consider the advantages that newly emergent stent coatings might offer, and whether targeting specific patient subgroups with unique antiproliferative agents may provide the best chance of limiting restenosis in high risk subgroups. Finally, we consider future strategies to prevent restenosis, with a movement away from the antiproliferative approach, and toward accelerating endothelialization.
Smith
Elliot J
EJ
London Chest Hospital, Barts and the London NHS Trust, London, UK.
Rothman
Martin T
MT
D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D020099:Coated Materials, Biocompatible; D003327:Coronary Disease / Q000628:therapy*; D023903:Coronary Restenosis / Q000503:physiopathology / Q000517:prevention & control*; D005544:Forecasting; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D017239:Paclitaxel / Q000627:therapeutic use; D012307:Risk Factors; D020123:Sirolimus / Q000627:therapeutic use; D015607:Stents / Q000639:trends
D000903:Antibiotics, Antineoplastic; D020099:Coated Materials, Biocompatible; D007166:Immunosuppressive Agents; D017239:Paclitaxel; D020123:Sirolimus