Evolution of Drug-Eluting Stent Drug Elution Profile: Is a Crystalline Drug Form the Ideal Solution?

Abstract

Since its introduction into clinical practice, coronary angioplasty has seen game-changing advances incomparable to any other medical technology. In particular, the progression from balloon angioplasty to stent technology has not only seen significant advances in technology but, more importantly, improved patient outcomes. The introduction of the drug-eluting stent (DES) has further pushed the technology to a new standard of care. However, even in the current day, top performing DESs still have several limitations. Their safety has been limited by suboptimal polymer biocompatibility, delayed stent re-endothelialisation, and local drug toxicity, leading to adverse clinical outcomes such as very late stent thrombosis, allergic reactions, and chronic inflammation. In addition, current DESs have a consistent yearly increase in late restenosis and revascularisations. Furthermore, durable polymer coatings used in first-generation DESs have been associated with mechanical complications and non-uniform coating, resulting in drug loss and poor distribution. As a consequence, in recent years, the focus of research has been on the development of novel drug carrier systems including absorbable (or biodegradable) polymer coatings and non-polymeric stent surfaces. Additional improvements have included the development of more modern stent platforms. Optimised drug delivery requires a combination of refined stent designs and drug delivery technology. The combination of highly-refined bare-metal stent designs and polymer coating materials have been two areas of focus for the development and improvement of next-generation DESs. Despite all the changes in stent design and polymer materials, there has been little done in the past 15 years to improve drug elution profiles. The need for new advancements in DES design to overcome late event occurrence, and possibly even improve on the clinical outcomes of current DESs, has led to interest in moving away from the standard drug elution profile to explore alternatives. A new manufacturing technique that may have overcome traditional limitations has led to the development of a novel stent platform. This review will explore the principles, device technology, and clinical data to date on a crystalline form of the anti-restenotic drug for stent implantation. This approach could truly be game changing due to an improved elution pharmacokinetic profile, as well as reduced local toxicity and improved long-term biologic arterial wall response.