Why do animal models of post-angioplasty restenosis sometimes poorly predict the outcome of clinical trials?

Abstract

Time for primary review 22 days. The 20th anniversary of percutaneous transluminal coronary angioplasty (PTCA), first introduced by Andreas Gruentzig MD, was recently celebrated. Since its introduction, millions of people have been successfully treated by PTCA. Despite its overwhelming success, 30 to 50% of patients develop restenosis, a rate that has changed little since the introduction of the technique. After 20 years of dramatic technical refinement and intensive research, we still do not know why a dilated artery will maintain patency and not develop restenosis or will develop restenosis. The lack of understanding about restenosis has often been attributed to inappropriate experimental models, incomplete or incorrect analysis of the models that has led to a focus on the wrong pathophysiologic target [1–4]. In the review, we will describe the various animal models used to study restenosis, and clarify the limitations and advantages of each in order to better delineate the ideal model of experimental angioplasty and restenosis. While outstanding reviews have already been written on this subject within the last five years [5–8], this review will be different from the former ones because it will take into account the following major changes: Stent-related restenosis, which is different from balloon-related restenosis, and arterial remodeling [9–12]. Arterial remodeling has transformed our understanding of restenosis and is of great clinical relevance, as shown by the good concordance between experimental data and human data obtained by intravascular ultrasound [13–19]. Before angioplasty started, balloon abrasion with endothelial denudation represented the gold standard for studying the response to vascular injury and smooth muscle cell proliferation and migration [20–25]. The idea of balloon angioplasty seemed to be a questionable method, and the occurrence of restenosis was not a surprise. Thus, experimental models of restenosis preexisted the clinical recognition of restenosis after angioplasty. … * Corresponding author. Tel.: 33609664209; E-mail: antoine.lafont@bcc.ap-hop-paris.fr