The Elusive Late Benefit of Biodegradable Polymer Drug-Eluting Stents

Article, see p 325 D rug eluting stents (DES), the standard-of-care stents in contemporary percutaneous coronary intervention, significantly reduce the risk of restenosis in comparison with bare metal stents (BMS).However, first-generation durable polymer (DP) DES were associated with high rates of very late (>1 year) events such as restenosis, stent thrombosis, and neoatherosclerosis, events attributed to a persistent inflammation/hypersensitivity reaction to the polymer. 1 The solutions to this polymer-related problem proceeded in 3 directions: (1) development of more biocompatible DP that reduces inflammation and promotes faster healing; (2) development of biodegradable (BP) polymer that biodegrades after drug elution, leaving behind a BMS-like stent; and (3) development of polymer-free DES where the drug is delivered without a polymer and is therefore a BMS-like stent.The clinical gains from improvement in the polymer-related aspects of stent design have been apparent.The second-generation DP-DES have lower risk of restenosis, stent thrombosis, myocardial infarction (MI), and death in comparison with BMS or first-generation DP-DES. 2,3Despite these excellent results with the second-generation DP-DES, major adverse cardiovascular events continue to accrue beyond 1 year at a steady rate.This has been attributed to continued low-grade peri-strut inflammation and promotion of neoatherosclerosis with the second-generation DP-DES.As such, BP-DES were touted as the future of DES technology. 4linical trials of BP-DES showed lower restenosis and stent thrombosis in comparison with the first-generation DP-DES, although the results have been variable. 2However, the more important question has been the comparison of BP-DES with the second-generation DP-DES.Cumulative data from meta-analyses of randomized trials suggest, at best, the noninferiority of BP-DES in comparison with second-generation DP-DES. 5Given the short duration of these trials, many have posited that the benefits of BP-DES will be seen at longer duration of follow-up after the polymer fully biodegrades (over months to years depending on the polymer). 6he 10-year outcomes of the ISAR-Test 4 trial (Intracoronary Stenting and Angiographic Results: Test Efficacy of 3 Limus-Eluting Stents) in the current issue of Circulation 7 provide further insights into this question.The ISAR-Test 4 trial enrolled 2603 patients with coronary artery disease who were randomly assigned 2:1:1 to the Yukon Choice PC stent (a BP-DES coated on the abluminal surface of a stent [87 µm thick] with a unique microporous surface) versus the Xience stent (a second-generation DP-DES [81 µm thick]) versus the Cypher stent (a first-generation DP-DES [140 µm thick]).The trial showed noninferiority of the BP-DES in comparison with DP-DES at 1 year and concluded that "the results provide a framework for testing the potential clinical advantage of BP-DES over the medium to longterm." 6At 10 years follow-up, the second-generation DP-DES, and the BP-DES,