Design Criteria for the Ideal Drug-Eluting Stent

https://doi.org/10.1016/j.amjcard.2007.08.016Get rights and content

The deployment of drug-eluting stents (DESs) is an integral treatment option for patients with coronary artery disease. Although the development and testing of the first-generation DESs focused to a considerable degree on efficacy parameters, including restenosis, recent concerns over late clinical events have prompted a refinement of the design criteria for succeeding generations of these devices. This review assesses design criteria for the ideal DES from 3 complementary perspectives: deliverability, efficacy, and safety. Most new investigational balloon-expandable DES systems have lowered crossing profiles by thinning stent struts using a cobalt chromium alloy, while investigational self-expanding DESs often use nitinol as the platform material. Stents designed to be fully biodegradable are also being developed, with deliverability and performance to be determined in future clinical trials. Refinements in bifurcation-dedicated stents will secure branch accessibility to offer better deliverability in complex lesion morphologies. Experimentation in stent design is already realizing multiple-lesion stenting and the in situ customization of stent length. Rather than simply targeting further reductions in restenosis rates, efforts to improve efficacy are shifting toward a lesion-specific approach, including the design of stents dedicated to bifurcation lesions. Another future direction is a disease-specific approach, or an approach using DESs as local drug-delivery devices. The identification of long-term safety issues with the first-generation DESs has reignited clinical interest in the development of stents that are more biologically based, including fully biodegradable stents and stents using biomimetic and biodegradable polymers. Important performance criteria for future DES agents include more cell-type specificity, broader safety margins, and greater facility at promoting endothelialization and healing.

Section snippets

Deliverability

Stent deliverability is one of the most under-recognized requirements for intracoronary stent technology4 and as such represents one of the key properties necessary for the ideal DES. Stents can perform their function only after deployment in target lesions. The first-generation DESs, with insufficient deliverability and lesion accessibility of their balloon-expandable delivery systems, may occasionally be limited in providing optimal clinical benefit. The serious procedural complications

Efficacy

The primary objective in the design of first-generation DESs was to decrease the neointimal formation seen with BMSs while maintaining an effective luminal dimension. Were it the case that stent dimensions remained static after deployment, the efficacy of the DES could be measured by the degree of inhibition of neointimal growth. The efficacy of the next-generation DES systems—biodegradable, for example, or based on platforms with thinner struts—may be influenced as well by the degree of

Safety

As clinical experience and longer term follow-up have accumulated, safety has emerged as an important issue with the DES. Several reports have emphasized the possible increase in the frequency of late stent thrombosis,1, 2, 3 occurring >1 year after stent implantation.

Addressed from the perspective of optimizing stent design, safety is a challenging issue. First, there are no established animal models that can reliably predict the safety profile of the DES in humans. Second, the recent

Conclusion

Current approaches to DES development were reviewed in this report. Although first-generation DESs placed great emphasis on efficacy, long-term safety issues have arisen, making the DES stand in an exquisite balance among the occasionally conflicting key properties of deliverability, efficacy, and safety. A careful reexamination of research findings, as well as a redefinition of safe and effective outcomes, will lead future stent technology in the optimal direction. There is no doubt that the

Author Disclosures

The authors who contributed to this article have disclosed the following industry relationships.

Junya Ako, MD, has no financial arrangement or affiliation with a corporate organization or a manufacturer of a product discussed in this supplement.

Heidi N. Bonneau, RN, MS, has received honoraria from Medtronic, Inc. and Boston Scientific.

Peter J. Fitzgerald, MD, PhD, has served as a consultant for Cordis Corporation, Boston Scientific, Abbott Vascular, Medtronic, Inc., CardioMind, Inc., REVA

References (52)

  • D.W. Park et al.

    Results and predictors of angiographic restenosis and long-term adverse cardiac events after drug-eluting stent implantation for aorto-ostial coronary artery disease

    Am J Cardiol

    (2007)
  • R.A. Costa et al.

    Bifurcation coronary lesions treated with the “crush” technique: an intravascular ultrasound analysis

    J Am Coll Cardiol

    (2005)
  • R. Koster et al.

    Nickel and molybdenum contact allergies in patients with coronary in-stent restenosis

    Lancet

    (2000)
  • J.C. Palmaz et al.

    Influence of stent design and material composition on procedure outcome

    J Vasc Surg

    (2002)
  • M.H. Sketch et al.

    Evaluation of the Medtronic (Driver) cobalt-chromium alloy coronary stent system

    Am J Cardiol

    (2005)
  • K.W. Lau et al.

    Clinical impact of stent construction and design in percutaneous coronary intervention

    Am Heart J

    (2004)
  • M. Joner et al.

    Pathology of drug-eluting stents in humans: delayed healing and late thrombotic risk

    J Am Coll Cardiol

    (2006)
  • P.W. Serruys et al.

    The effect of variable dose and release kinetics on neointimal hyperplasia using a novel paclitaxel-eluting stent platform: the Paclitaxel In-Stent Controlled Elution Study (PISCES)

    J Am Coll Cardiol

    (2005)
  • J. Aoki et al.

    Endothelial progenitor cell capture by stents coated with antibody against CD34: the HEALING-FIM (Healthy Endothelial Accelerated Lining Inhibits Neointimal Growth-First in Man) Registry

    J Am Coll Cardiol

    (2005)
  • A. Kastrati et al.

    Analysis of 14 trials comparing sirolimus-eluting stents with bare-metal stents

    N Engl J Med

    (2007)
  • B. Lagerqvist et al.

    Long-term outcomes with drug-eluting stents versus bare-metal stents in Sweden

    N Engl J Med

    (2007)
  • W.H. Maisel

    Unanswered questions—drug-eluting stents and the risk of late thrombosis

    N Engl J Med

    (2007)
  • W. Schmidt et al.

    Trackability, crossability, and pushability of coronary stent systems—an experimental approach

    Biomed Tech (Berl)

    (2002)
  • P. Urban et al.

    Safety of coronary sirolimus-eluting stents in daily clinical practice: one-year follow-up of the e-Cypher registry

    Circulation

    (2006)
  • M. Yamasaki et al.

    Safety and feasibility of novel guidewire-based self-expanding stent delivery system

    Am J Cardiol

    (2005)
  • A. Abizaid et al.

    The CardioMind coronary stent delivery system: stent delivery on a .014” guidewire platform

    EuroIntervention

    (2007)
  • Cited by (76)

    • Medical Device Technologies: A Systems Based Overview Using Engineering Standards

      2020, Medical Device Technologies: A Systems Based Overview Using Engineering Standards
    View all citing articles on Scopus

    Statement of author disclosure: Please see the Author Disclosures section at the end of this article.

    View full text