Chapter 39: The Vascular Biology and Clinical Efficacy of Drug-Eluting Stents for the Treatment of Peripheral Arterial Disease

INTRODUCTION

Nearly 10% of the population older than 65 years has atherosclerotic lower extremity peripheral arterial disease. Older patients and those with risk factors may have up to a 25% incidence of lower extremity peripheral arterial disease.¹ Percutaneous vascular interventions are rapidly emerging as a less invasive therapy for symptomatic lower extremity occlusive arterial disease.^2,3,4 Despite recent advances, restenosis remains a significant problem with catheter-based revascularization. By delivering high local doses, drug-eluting stents have the potential to overcome the limitations of restenosis and advance stent-based therapies for lower extremity peripheral arterial disease (Table 39-1).

There is interest in the applicability of drug eluting stent (DES) in other arterial beds as well. Most studies and case series have focused on the efficacy in the renal arteries, intracranial circulation, and extracranial carotid or vertebral arteries. To date, the bulk of clinical studies have been in the evaluation of drug-eluting stents to reduce restenosis in the coronary arteries, with dramatic results, which are simultaneously changing the treatment paradigm for multivessel coronary artery disease and raising long-term safety concerns.

MECHANISM OF BALLOON ANGIOPLASTY AND STENTING

Balloon angioplasty of occlusive arterial disease results in a lumen diameter gain through several mechanisms. Angioplasty compresses the atherosclerotic plaque, shifting it laterally and axially, as well as causing a "controlled" intimal and medial dissection.⁵ Angioplasty is, however, limited by the acute elastic recoil properties of the arterial wall with up to a 40% loss in lumen area.^5,6 Flow-limiting dissections can occur and may lead to acute or subacute vessel closure.⁷ As a scaffold, stents improve the initial results of percutaneous interventions by increasing the arterial lumen and tacking up intimal flaps between the stent and the vessel wall. The scaffolding properties of stents virtually eliminate acute arterial recoil and reduce the subsequent risk of acute or subacute vessel closure.^5,7,8,9

RESTENOSIS PATHOPHYSIOLOGY

Restenosis is characterized by three processes: acute vessel recoil, late vessel remodeling (negative/constrictive remodeling), and neointimal hyperplasia.^5,7,10 Stents effectively eliminate acute vessel recoil and negative vessel remodeling. In-stent restenosis is, therefore, almost entirely owing to neointimal hyperplasia.^8,11,12 Compared to balloon angioplasty, stents can cause more tissue proliferation by virtue of greater chronic injury to the vessel wall. The long-term effectiveness of stents is mitigated by this "late loss" of the arterial lumen because of tissue proliferation within the stent.

The pathophysiology of vascular repair mechanisms after angioplasty and stenting has been extensively studied in a variety of experimental models. Angioplasty and ...