Article

A new generation of drug-eluting stents: Indications and outcomes of bioresorbable vascular scaffolds

Author and Disclosure Information

ABSTRACT

Drug-eluting stents (DES) are increasingly being used as a less invasive alternative to coronary artery bypass grafting. Early generation DES had durable polymers that provided acceptable efficacy outcomes but had high rates of stent thrombosis leading to myocardial infarction and death. Second-generation DES have improved outcomes by reducing stent thrombosis and recurrent stenosis. Newer DES with biodegradable polymers have similar efficacy as second-generation DES, but have higher rates of stent thrombosis. This review compares outcomes of bioresorbable scaffolds and looks at stent technology developments that may improve outcomes.

KEY POINTS

  • Complications with first-generation durable polymer DES—stent thrombosis and restenosis with target lesion revascularization—led to the development of bioresorbable stents.
  • Bioresorbable and durable polymer metallic DES have similar rates of efficacy and of stent thrombosis.
  • Bioresorbable DES should be placed in appropriate patient populations and lesion subsets, and limited to arteries larger than 2.25 mm.


 

References

The development of a new generation of drug-eluting stents (DES) has had a dramatic impact on the number of stents used for percutaneous transluminal coronary angioplasty for the treatment of coronary artery disease (CAD). But even second- and third-generation DES fall short when compared with coronary artery bypass grafting (CABG) with regards to the need for repeat reavascularization. CABG is advantageous because it bypasses the entire disease segment of the vessel. Thus for multivessel complex CAD, it is still considered the best choice. Nevertheless, most patients prefer the less-invasive option of stents, so practitioners need to provide the best stent available.

There are 3 primary criteria for DES selection:

  • Efficacy for a broad range of patients and lesion complexities that primarily provides consistency in improving measures of angiographic and clinical efficacy
  • Safety as determined by the following:
    • Enable healing and promote endothelialization
    • Permit functional endothelium
    • Obtaining complete apposition
    • Reduction or elimination of late and very late stent thrombosis
    • Minimizing the need for long-term dual antiplatelet therapy
  • Performance provided by reliable delivery capabilities to the lesion site.

GREAT EXPECTATIONS

New DES must be shown to be superior to previous generation stents. Although preclinical endothelialization and other mechanistic surrogates are good enough to claim an improvement, the traditional method is to compare clinical outcomes with the new stent versus the existing stent in a randomized clinical trial.

Evolution of drug-eluting stents
The first-generation DES demonstrated superiority over bare-metal stents and became the default stent of choice for revascularization. But complications of first-generation stents such as stent thrombosis and late restenosis led to the development of second-generation DES, which demonstrated superiority over the first-generation DES. Although third-generation DES have been introduced with bioresorbable polymers, these have not improved clinical outcomes when compared with second-generation DES. Overall, the outcomes of second-generation DES are good, with low event rates that challenge the ability to demonstrate further improvement or superiority with third-generation DES. Nevertheless, there is an ongoing effort to continue to improve the current stents with thinner struts and more biocompatible polymer, biodegradable polymer, or polymer-free stents. Table 1 shows the evolution of DES from the nonbiodegradable polymer-based stents to the bioresorbable scaffolds, which are completely eliminated from the body.

PROBLEMS WITH DURABLE POLYMER STENTS

Complications with durable polymer DES have included increased local inflammation and neoatherosclerosis. There are reports of subacute stent thrombosis due to lack of adequate expansion and stent apposition. Also reported was late thrombosis, resulting in increased rates of myocardial infarction and death.

These issues motivated engineers to improve and iterate the DES technology. One important technological change is the decrease in strut thickness from 140 µm to as low as 60 µm. The thickness of the polymer coating also has been reduced. The polymer became thinner, more biocompatible, and in some stents, only abluminal. Further developments were to substitute the durable polymer with a biodegradable polymer and perhaps even design a polymer-free stent.

BIORESORBABLE POLYMERS EMERGE

The time course for resorption of bioresorbable polymers ranges from 2 to 15 months, but they all degrade, which should improve long-term outcomes. A meta-analysis of data from the LEADERS trial and ISAR-TEST 3 and 4 found that the bioresorbable polymer stents were associated with significantly lower rates of target-lesion revascularization (P = .029) and stent thrombosis (P = .015) than durable polymer DES at 4 years after implantation.1 Those results led to the notion that stents with a biodegradable polymer would result in lower rates of stent thrombosis than durable polymer stents; however, that was not the case when stents with biodegradable polymers were compared with second-generation DES.

In the COMPARE II trial,2 the rates of stent thrombosis and target-lesion revascularization were not statistically different for the thick-strut biodegradable polymer biolimus-eluting stent (Nobori) compared with the second-generation thin-strut permanent-polymer stents (Xience). In the CENTURY II trial,3 a third-generation biodegradable sirolimus-eluting stent (Ultimaster) had stent thrombosis rates similar to those of a durable polymer everolimus-eluting stent (Xience) 300 days after insertion (4.36% vs 5.27%, respectively). Target-lesion revascularization rates were also about the same for the stents. In the EVOLVE II trial comparing the thin-strut biodegradable everolimus-eluting stent (Synergy) vs the thin-strut permanent-polymer everolimus-eluting stent (Promus), the 12-month target lesion failure rates for the stents were essentially the same.4

Next Article:

Improving the safety and efficacy of robotically assisted mitral valve surgery

Related Articles