Mechanisms and prevention of restenosis: from experimental models to clinical practice

Percutaneous transluminal coronary angioplasty (PTCA) was first introduced by Andreas Gruentzig in 1977 [l] as an alternative form of myocardial revascularization for patients with coronary artery disease. During the early years of its application, PTCA was limited to patients with single proximal coronary artery disease, well preserved left ventricular function, and stable angina refractory to medical treatment. Almost twenty years later, PTCA has become a well established technique for myocardial revascularization of patients with unstable angina [2], patients with an evolving myocardial infarction [3], patients with multivessel disease [4], and patients with depressed left ventricular function [5]. However, PTCA remains limited by restenosis that occurs in 30-60% of cases despite a successful procedure [6-g]. Assuming 500000 PTCA procedures per year in the United States [lo], more than 150000 patients develop restenosis every year. Although some restenoses may be silent, most of these patients present with recurrent angina and a significant proportion will need a new revascularization procedure. Decreasing the rate of restenosis would sharply lower the long-term cost of PTCA; in the United States, a reduction of the rate of restenosis from an hypothetical 33% to 25% might save as much as $750 million annually [IO]. Numerous agents have been used to prevent restenosis, and the results of more than 40 multicenter randomized clinical trials have now been published [11,12]. Despite intensive investigation in this area, no pharmacological therapy has yet been found to be useful in preventing restenosis. The purpose of this report is twofold: first, to review the available information relevant to the mechanisms of restenosis, and, second, to review the strategies currently being explored as possible approaches to the control of coronary restenosis after PTCA.