7 Restenosis and Drug-Eluting Stents
Restenosis
The second component of restenosis, recoil and negative remodeling of the arterial wall is inhibited by stents. Compared to balloon angioplasty, stents have reduced restenosis from 40% to 50% after percutaneous transluminal coronary angioplasty (PTCA) to 20% after bare-metal stenting. Drug-eluting stents (DESs) have brought restenosis rates to <10% in most patient subgroups. Restenosis still occurs inside stents (called in-stent restenosis [ISR]) mostly, if not exclusively, as a result of endothelial cell proliferation. Rarely does vascular recoil make a contribution, but it must be considered in treating the ISR lesion. Restenosis is not device-specific but rather a function of the anatomic substrate and the type of injury produced (Fig. 7-1).

Figure 7-1 Interventional devices and presumed mechanisms of action of arterial plaque in vessel wall lead to restenosis. The indication of immediate outcome and restenosis rates depend on both the device and the arterial substrate encountered.
(From Waller BF, Pinkerton CA, Orr CM. Restenosis 1 to 24 months after clinically successful coronary balloon angioplasty: A necropsy study of 20 patients. J Am Coll Cardiol 1991;17:58–70.)
Definitions of Restenosis
Angiographic Restenosis
The late loss index is the loss at the lesion site divided by the amount of acute gain (Fig. 7-2). The loss index is accepted as the most sensitive measure of the effectiveness of the technique and should range from 0.4 to 0.6 mm for balloon angioplasty. The lower the loss index is, the more effective the antirestenosis treatment will be.
Intravascular ultrasound (IVUS) imaging is superior to angiography for anatomic and morphologic restenosis definitions. Recent IVUS studies have shown that an important component of restenosis is vessel recoil, a feature prevented by stenting. Normal vessel modeling maintains the coronary lumen. Late negative remodeling of the injured vessel is also prevented by stenting (Figs. 7-3 and 7-4).

Figure 7-3 The Glagov phenomenon. According to serial intravascular ultrasound, normal segments showed proximal enlargement of the vessel as plaque volume increases. Vascular dilatation is compensated for by substantial plaque formation inside the vessel wall leaving the vessel’s angiographic appearance unchanged and normal looking.
(From Glagov S, Wisenberg E, Zarins CK, et al. Compensatory enlargement of human atherosclerotic coronary arteries. N Engl J Med 1987;316:1371–1375.

Figure 7-4 Adequacy of arterial remodeling with respect to changes in vessel size.
(From Schwartz RS. Pathophysiology of restenosis: interaction of thrombosis, hyperplasia, and/or remodeling. Am J Cardiol 1998;81:16E.)
Time Course
Different mechanisms produce restenosis in a time-dependent manner. Early restenosis is due to thrombus, whereas late restenosis is related more to remodeling (Fig. 7-5).

Figure 7-5 The four phases of vascular repair after stent-induced arterial injury in terms of time after stenting. A, Platelet-rich thrombus accumulates at areas of deep strut injury and peaks at 3 to 4 days after stent deployment, accounting for most early lumen loss. B, Coincident with thrombus deposition, inflammatory cells are recruited to the injury site, both at and between stent struts. At 3 to 7 days after stenting, the surface-adherent monocytes (SAMs) migrate into the neointima as tissue-infiltrating monocytes (TIMs) and remain in place. C, Proliferation of smooth muscle cells and monocyte macrophages within the neointima peaks at 7 days after implantation and continues above baseline levels for weeks thereafter. D, Collagen deposition in the adventitia and throughout the tunica media and neointima leads to arterial shrinkage or remodeling, causing compression of the artery on stent struts from without.
(Modified from Garasic J, Edelman E, Rogers C. Stent design and the biologic response. In Beyar R, Keren G, Leon M, Serruys PW, eds. Frontiers in interventional cardiology. London: Martin Dunitz, 1997: 95–100.)