Drug-eluting stents: costs versus clinical benefit.

Since the advent of coronary angioplasty in 1977, the procedure has changed from an uncommonly used method of treating simple discrete lesions1 to one that challenges surgical revascularization.2 Step by step, major anatomic obstacles have fallen as this procedure has been applied to an expanding patient population. Technical breakthroughs including steerable and movable guidewires, low-profile balloon shafts, atherectomy devices, and ultimately stent implantation have made percutaneous coronary intervention (PCI) more successful, safer, and more durable.3 Unfortunately, 2 major obstacles have limited PCI; these are chronic total occlusions and restenosis. The year 2002 will be remembered as the year in which one of these remaining obstacles fell. The recent publication of the RAVEL study4 (RAndomized study with the sirolimus-eluting VElocity balloon-expandable stent in the treatment of patients with de novo native coronary artery Lesions) and the presentation of the SIRIUS5 (a multicenter randomized double-blind study of the SIRolImUS-coated Bx Velocity stent in the treatment of patients with de novo coronary artery lesions) and TAXUS II6 studies provide optimism that the “Achilles heel of angioplasty” has finally been conquered. As we embark on this new era of PCI, all clinicians are grappling with which patients and lesions are most appropriately treated using these effective and expensive new stents. We will attempt to briefly review the initial clinical data and formulate guidelines for rational use of drug-eluting stents (DES) that would be relevant to clinical practice in the immediate future. Anatomy of a DES A DES is an advanced biotechnology platform consisting of a 3-component system, as follows: (1) a stent with catheterbased deployment and optimized features for enhanced deliverability to the lesion site, (2) a drug-carrier vehicle that permits elution of the drug or biologic into the vessel wall at the required concentrations and kinetic profile, and (3) a pharmacological agent possessing specific properties that interfere with local neointimal formation. Most DES systems utilize current-generation commercial stents and delivery systems. In the near future, stent design features and balloon catheter delivery systems will be importantly modified to accommodate the specialized needs of homogeneous sitespecific drug delivery into the subjacent vessel wall. The spectrum of drug-carrier vehicles ranges from known biocompatible polymers to multiple innovative newly engineered modalities, including biomimicry with phosphorylcholine coverings and nanoporous ceramics. Most importantly, the drug carrier should not significantly alter the mechanical and deliverability characteristics of the stent and should facilitate precise drug delivery without inducing independent pathobiological effects such as inflammation or thrombosis. Several different classes of pharmacological agents are being closely scrutinized, starting with cell culture studies, progressing to porcine coronary models, and culminating in phase I safety, first-in-human clinical experiences. The drug classes can be divided into antiproliferative agents, anti-inflammatory (or immunomodulating) agents, antimigratory agents that affect extracellular matrix properties, and prohealing agents that encourage more rapid endothelializa-