Drug-eluting Stents: Will the transformation to bioabsorption make durable polymers obsolete?

Abstract

It's been over a decade since drug-eluting stents (DES) were introduced into the clinical practice of percutaneous coronary intervention for the treatment of coronary artery lesions. With significant reductions in restenosis rates and the need for repeat revascularizations, the technology was disseminated globally at an unprecedented rate [1]. Soon after, reports of early and late stent thrombosis curbed the enthusiasm and mandated selective DES uses and prolonged dual antiplatelet therapy (DAPT) for at least 12months [2]. This strategy significantly reduced stent thrombosis rates, albeit at the price of bleeding, which has often led to premature DAPT discontinuation [3]. Additionally, first-generation DES, Cypher and Taxus, reported a stent thrombosis increasing hazard of 0.6 per year up to 5 years and even higher rates of target lesion failure [4]. Firstgeneration DES were then replaced with second-generation DES that utilize a thinner cobalt chromium or platinum chromium alloy, sirolimus analogue drugs, such as everolimus and zotarolimus, and a thinner and more biocompatible polymer layer. Despite these iterations, the requirement for prolonged DAPT did not change. At the same time, the hazard ratios for stent thrombosis and target vessel failure were attenuated, but not eliminated, especially in the more complex patient and lesion subsets [5,6]. The question remains, “What factors contribute to the development of the late events seen in second-generation DES?” Is it the metal? The polymer? Or is it the drug? For BMS, target vessel failure occurs within the first 6–12 months, and events beyond that are rare. With second-generation DES, the drug is gone within the first 6 months and complete healing is usually attained at 12 months. This suggests that the culprit for these late events (N12 months) is most likely the polymer, which continues to irritate the vessel wall causing low grade inflammation and subsequently neoatherosclerosis. The polymers used in first-generation DES were associated with a high degree of inflammation, which often resulted in vessel wall toxicity, target lesion failure, and late stent thrombosis. Nevertheless, the polymers used in the second-generation DES, such as BioLinx and fluoropolymer, are proven to be more biocompatible. More specifically, the fluoropolymer used in Xience V (Abbott Vascular) and Promus Element stents (Boston Scientific) have further claimed to have antithrombotic properties and protection from stent thrombosis when compared to BMS [7]. However, the data to support this claim are rather weak and did not result in a change in the recommended duration of DAPT for such stents. Further, in the Prospective, Randomized, Multicenter Trial to Assess