The introduction of bare-metal stents (BMS) provided a solution to the notable limitations of balloon angioplasty in patients undergoing percutaneous coronary intervention (PCI), notably acute occlusion, and improved the rate of reoccurrence of narrowing of the target vessel (restenosis) caused by smooth-muscle-cell proliferation with resultant neointimal hyperplasia. However, there is still significant room for improvement, which also would translate into a reduction of the still relatively high rates of clinically symptomatic cases requiring target-lesion revascularisation.1
Clinical trials have shown that the first commercially approved drug-eluting stents (DES) have been successful at using a durable polymer to deliver drugs with anti-inflammatory and antiproliferative effects to the site of injury.2 This is intended to reduce the occurrence of restenosis compared with BMS3 by preventing stent-related neointimal hyperplasia while preserving vessel architecture compromised by PCI.3 However, such an achievement appears to be accompanied by a slight increase in the risk of developing stent thrombosis in the long term, particularly one year following implantation.4
The sustained, immediate and direct exposure of the vessel wall to the polymer has been reported to be associated with complications, including either a non-specific monocyte–macrophage-predominant) or a hypersensitivity-related5 inflammatory response to the polymer as a foreign object, delayed arterial healing5 as reflected by persistent fibrin deposition, persistent platelet activation, delayed endothelialisation and positive vessel remodelling with late acquired stent malapposition,5,6 all of which could underlie stent thrombosis occurring months to years after stent implantation (see Figure 1).
In addition, the physical properties of the polymer coating and its integrity under mechanical stress can have clinical consequences. Stent expansion may be affected if the polymer surface coating of the stent is not uniform or is webbed, and webbing of the polymer surface has been implicated in increased rates of peri-procedural myocardial infarction.7 Mechanical stresses during delivery of the stent may lead to delamination and fragmentation of the polymer coating (see Figure 2), which may hamper the programmed uniform local drug distribution and therefore increase neointimal hyperplasia.8 All of these factors may potentially add to the risk of inflammation and thrombosis. Therefore, there is a requirement to develop a bioadsorbable polymer that will ideally minimise binding to the stent, release the drug effectively in a similar way to durable polymers and totally degrade over the short term. Abolition of exposure to a permanent polymer might prevent the observed clinical pathology seen with the utilisation of durable polymers in DES.
New stent designs that eliminate the need for surface polymer coating utilising only the necessary amount of polymer to ensure a sustained and appropriate release of therapeutic drug (thereby preventing restenosis) may aid in the deliverability and safety of the device. The combination of such stent designs and the absence of a permanent polymer might potentially prevent the problems associated with polymer-related inflammation and hypersensitivity and other complications.9