Pharmacological treatment for prevention of restenosis

Abstract

Coronary artery disease (CAD) is the leading cause of mortality and morbidity among adults in the Western world. Coronary artery bypass grafting and percutaneous coronary interventions (PCI) have gained widespread acceptance for the treatment of symptomatic CAD. There has been an explosive growth worldwide in the utilisation of PCI, such as balloon angioplasty and stenting, which now accounts for over 50% of coronary revascularisation. Despite the popularity of PCI, the problem of recurrent narrowing of the dilated artery (restenosis) continues to vex investigators. In recent years, significant advances have occurred in the understanding of restenosis. Two processes seem to contribute to restenosis: remodelling (vessel size changes) and intimal hyperplasia (vascular smooth muscle cell [VSMC] proliferation and extracellular matrix [ECM] deposition). Despite considerable efforts, pharmacological approaches to decrease restenosis have been largely unsuccessful and the only currently applied modality to reduce the restenosis rate is stenting. However, stenting only prevents remodelling and does not inhibit intimal hyperplasia. Several potential targets for inhibiting restenosis are currently under investigation including platelet activation, the coagulation cascade, VSMC proliferation and migration, and ECM synthesis. In addition, new approaches for local drug therapy, such as drug eluting stents, are currently being evaluated in preclinical and clinical studies. In this article, we critically review the current status of drugs that are being evaluated for restenosis at various stages of development (in vitro, preclinical animal models and human trials).

• cell proliferation
• extracellular matrix
• PTCA
• restenosis
• smooth muscle cells
• stent