2006 James B. Herrick Award and Lecture—Drug-Eluting Stents: The Beginning of the End or the End of the Beginning?
In 2003–2004, drug-eluting stents (DES) were approved by regulatory bodies in the European Union and United States. Pivotal studies in the preceding year had demonstrated a major treatment effect (60% to 80%) on angiographic restenosis irrespective of the type of lesion or clinical syndrome. Interventional cardiologists worldwide swiftly embraced this new modality of treatment, with market penetration of 30% to 90%. This disruptive technology—without evidence base— has already had a major impact on our approach to coronary revascularization. Patients traditionally referred for surgery are now revascularized percutaneously. But in 2008–2009, results of major trials comparing percutaneous coronary intervention with coronary artery bypass grafting (SYNTAX, FREEDOM, COMBAT, CARDIA) in patients with 3VD and/or LMS may confirm the value of DES in “surgical” patients, and the beginning of the end of a surgical era might be on the horizon. On the other hand, worrisome information about late stent thrombosis is currently emerging. The drugs used are potent cytostatic or cytotoxic agents with long-term detrimental effects on endothelialization. Large investigator-driven registries with long follow-up suggest an unabated rate of late stent thrombosis even after 3 years. New pharmacological strategies (nonpolymeric reservoir, dual-drug elution, use of antithrombotic and antiinflammatory agents) and new absorbable metallic or nonmetallic platforms are currently being tested. The primary goal is no longer “oncologic” inhibition of neointimal hyperplasia but the restitution of a healthy and functionally active endothelial lining (eg, by capturing progenitor endothelial cells), capable—in conjunction with prohealing drugs (eg, NO donors)—of modulating the healing process without the use of permanent metallic stents. From this viewpoint, we are just at the end of the pioneering phase of the first generation of DES…and the end of the beginning.