Risk prediction of in-stent restenosis among patients with coronary drug-eluting stents: current clinical approaches and challenges

ABSTRACT

Introduction: In-stent restenosis (ISR) has been one of the biggest limitations to the success of percutaneous coronary intervention for the treatment of coronary artery disease (CAD). The introduction of drug-eluting stent (DES) was a revolution in the treatment of CAD because these devices drastically reduced ISR to very low levels (<5%). Subsequently, newer generation DES treatments have overcome the drawbacks of first-generation DES, i.e. delayed endothelialization, and late stent thrombosis. However, the issue of late ISR, including neoatherosclerosis after DES implantation especially in high-risk patients and complex lesions, still exists as a challenge to be overcome.

Areas covered: We discuss the mechanisms of ISR development including neoatherosclerosis, past and current clinical status of ISR, and methods to predict and overcome this issue from pathological and clinical points of view.

Expert opinion: The initial drawbacks of first-generation DES, such as delayed endothelial healing and subsequent risk of late stent thrombosis, have been improved upon by the current generation DES. To achieve better long-term clinical outcomes, further titration of drug-release and polymer degradation profile, strut thickness as well as material innovation are needed.

KEYWORDS:

• Drug-eluting stent
• percutaneous coronary intervention
• coronary artery disease
• in-stent restenosis

Article highlights

• In-stent restenosis (ISR) has been one of the biggest limitations to the success of percutaneous coronary intervention. The introduction of drug-eluting stent (DES) reduced ISR incidence dramatically and subsequent newer generation DES have overcome the drawback of first-generation DES. However, ISR still has not been eliminated. A deeper understanding of ISR, in terms of the mechanisms, past and current clinical status, and risk factors is necessary to improve clinical outcomes.

• Vessel wall injury and foreign body-related inflammation are initiating factors in the restenotic process. The histopathologic character of DES-ISR is different from that of BMS-ISR and affects the accelerated development of neoatherosclerosis and late stent failure. Although both stents show neoatherosclerotic change, overall incidence of neoatherosclerosis is significantly greater and observed earlier in DES as compared to BMS. It might be related to the presence of anti-proliferative agents, which can cause endothelial cell dysfunction.

• Predictors of ISR can be classified into three categories: patient-related, lesion-related, and procedure/device-related factors. Two important patient-related factors are diabetes mellitus and chronic kidney disease. In terms of lesion-related factors, lesion calcification leads to poor clinical outcomes even in the newer generation DES era.

• There are two effective treatment strategies for ISR lesion: repeat DES stenting and angioplasty with DCB. Some trials have shown that repeat stenting with DES was more effective than angioplasty with DCB at reducing the need for TLR, whereas the rate of all-cause death, myocardial infarction were similar between the two strategies. Overall, DES-ISR is associated with higher rates of treatment failure as compared to BMS-ISR, regardless of the types of treatment.

Declaration of interest

CVPath Institute has received institutional research support from R01 HL141425 Leducq Foundation Grant; 480 Biomedical; 4C Medical; 4Tech; Abbott; Accumedical; Amgen; Biosensors; Boston Scientific; Canon USA; Cardiac Implants; Celonova; Claret Medical; Concept Medical; Cook; CSI; DuNing, Inc; Edwards LifeSciences; Emboline; Endotronix; Envision Scientific; Lutonix/Bard; Gateway; Lifetech; Limflo; MedAlliance; Medtronic; Mercator; Merill; Microport Medical; Microvention; Mitraalign; Mitra assist; NAMSA; Nanova; Neovasc; NIPRO; Novogate; Occulotech; OrbusNeich Medical; Phenox; Profusa; Protembis; Qool; ReCor Medical; Senseonics; Shockwave; Sinomed; Spectranetics; Surmodics; Symic; Vesper; W.L. Gore; Xeltis. A.V.F. has received honoraria from Abbott Vascular; Biosensors; Boston Scientific; Celonova; Cook Medical; CSI; Lutonix Bard; Sinomed; Terumo Corporation; and is a consultant to Amgen; Abbott Vascular; Boston Scientific; Celonova; Cook Medical; Lutonix Bard; Sinomed. Anne Cornelissen receives research grants from University Hospital RWTH Aachen. R.V. has received honoraria from Abbott Vascular; Biosensors; Boston Scientific; Celonova; Cook Medical; Cordis; CSI; Lutonix Bard; Medtronic; OrbusNeich Medical; CeloNova; SINO Medical Technology; ReCore; Terumo Corporation; W. L. Gore; Spectranetics; and is a consultant Abbott Vascular; Boston Scientific; Celonova; Cook Medical; Cordis; CSI; Edwards Lifescience; Lutonix Bard; Medtronic; OrbusNeich Medical; ReCor Medical; Sinomededical Technology; Spectranetics; Surmodics; Terumo Corporation; W. L. Gore; Xeltis. The other authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.