Pathophysiology and pharmacological approaches for prevention of coronary artery restenosis following coronary artery balloon angioplasty and related procedures

Percutaneous transluminal coronary angioplasty (PTCA) has become a mainstay in the treatment of ischemic heart disease, with an estimated 300,000 procedures performed annually in the United States. Despite significant advances in reducing the acute complications of percutaneous revascularization procedures with periprocedural medications and better techniques, chronic restenosis of dilated lesions remains a serious and frequent problem, occurring in 30% to 50% of cases. With a peak incidence between 1 and 4 months after PTCA, restenosis has been thought to reflect an exaggerated healing response to balloon injury, in which platelets and other cells secrete mitogens that induce smooth muscle cells from the media to migrate to and proliferate in the intima, compromising the coronary lumen and invoking ischemic symptoms. Several factors, including remodeling with compensatory arterial enlargement, normalization of wall shear stress, and recoil, are also likely to play keyroles. Based on these concepts, several pharmacological approaches directed at reducing the incidence of restenosis have been investigated. Although studies frequently report suppression of neointimal proliferation in animal models of balloon vascular injury, few drug approaches have met with clear success in clinical trials. This can be explained in several ways, including mistaken understandings of the pathophysiology of restenosis, gross histopathological dissimilarities between animal vascular injury models and clinical restenosis, and inadequate dosing. This report proposes to extensively review the vast literature on the subject to serve as a guide for clinicians to the pathophysiology of restenosis and the pharmacotherapeutic management of patients after PTCA and coronary atherectomy. Those drug approaches that currently show the most clinical promise and that warrant further investigation will be highlighted.