Insights Into Instant Restenosis: A Review Discussing the Pros and Cons of The Drug-Eluting Stent and Balloon

Restenosis in stents and balloons has been an emerging problem in the world, as in patients with acute coronary syndrome who underwent cutaneous intervention. There has been a continuous debate on the benefits of stents and balloons in PCI. It is important to notice drug-releasing treatment modalities, as they have a huge impact on the outcome and also on the debate between stents and balloons. It is important to weigh every criterion to have the best treatment modality for the patient to provide the best possible care. The advantages and disadvantages of drug drug-eluting balloons are also as important to discuss, as balloons mechanically fall short against acute retractions.

Restenosis is defined as the reduction in lumen diameter after percutaneous coronary intervention (PCI), whether or not a stent is implanted. In the absence of a strategy, it usually includes vascular remodeling and elastic recoil (ER); otherwise, it is determined by excessive tissue proliferation in the lumen of the stent, which is called "neointimal proliferation" [1]. Although the risk of restenosis of the new generation of drug delivery stents (DES) has been significantly reduced, DES has obvious shortcomings, such as the need for prolonged dual antiplatelet therapy (DAPT), delayed endothelial healing, late and very late stents, dislocation, and thrombosis of the stent thrombosis and emerging atherosclerosis [2]. Therefore, DEB aims to avoid the insertion of permanent foreign bodies into blood vessels, thereby preventing potential problems caused by DES. DEB is coated with a fine mixture of high-dose pharmacologically active antiproliferative drugs on the common bottom of the balloon. Through a single balloon inflation, the drug is transferred to the new intimal layer of the blood vessel wall, and the coronary intervention usually takes between 30 and 60 seconds. To avoid elastic retraction after DEB expansion, a bare metal stent (BMS) was subsequently used [2].

ISR classification

• Type I: focal 10mm in length intrastent
• IA articulation or gap
• IB margin
• IC focal body
• ID multifocal
• Type 2: diffuse >10 mm intrastent.
• Type 3: proliferative 10 mm extending beyond the stent margins.
• Type 4: Total occlusion of restenotic lesions with TIMI flow grade 0.

Treatment

Various treatment strategies have been developed for patients. These include POBA, balloon cutting or scoring, rotational atherectomy, and intravascular brachytherapy. However, these technologies have been largely replaced by DES as a result of their profound inhibition of the formation of new intima. For this reason, DES has become the standard of care for ISR treatment in many parts of the world, especially the ISR in the previous DES.

 Therefore, in the treatment of ISR, DEB is increasingly being used as an alternative treatment strategy, especially for the first generation of DES. Paclitaxel-releasing balloon (PEB) is currently the most common DEB in clinical practice and relies on the lipophilicity of paclitaxel, which helps it to rapidly transfer from the balloon to the tissue and ensure continued antiproliferative effects. indicate that the paclitaxel-coated balloon can reduce the area of the neointima without affecting the formation of the neo-endothelial of the strut [3,4]. Additionally, DEB can be used in the subset of injuries where DES cannot be administered or DES malfunctions, such as twisted blood vessels, small blood vessels, or long-term diffuse calcified lesions, which can lead to fracture of the stent; or when the stent blocks large collateral or bifurcated lesions. Weather [3].

The main factor that affects the effectiveness of the paclitaxel-releasing balloon catheter (PEB) is the method by which the paclitaxel is attached to the surface of the balloon catheter. Paclitaxel can be applied freely directly to the rough surface of a balloon catheter (DIOR® 1st generation; Eurocor, Bonn, Germany) or attached to a carrier, affecting its solubility and ability to penetrate the vessel wall. The American Academy of Cardiology (ACC)/American Heart Association (AHA)/Cardiovascular Angiography and Intervention (SCAI) guidelines and European guidelines (European Society of Cardiology - ESC) currently recommend DES for treating RIS, regardless of whether the initial stent is bare metal or DES. However, the evidence for this recommendation is weak, especially concerning DES stent restenosis. Many operators tend to use different types of DES to treat drug-eluting stent restenosis. This common practice is not based on evidence, and the ISAR DESIRE 2 trial (coronary artery stenting and angiography results: drug-eluting stent for ISR) did not show that the carmustine stent ISR (SES) was compared with other SES. eluting the stent with paclitaxel [5,6].  DES is more effective in the treatment of new coronary artery disease, but in terms of reducing the clinical outcome of the risk of MACE, TLR, MI, and mortality, DES is as effective as DEB in the treatment of SSI [2,3].

Advantages of using DEB

1. Avoid permanent implant problems that can cause inflammation and tissue growth.
2. Provide antiproliferative medications when needed, for example, immediately after balloon angioplasty causes barotrauma.
3. Avoid multiple stents.
4. Avoid the potential risk of stent corrosion.
5. In theory, the overlap of stents of different alloys can cause galvanic corrosion. DEB can stop it. However, these problems are theoretical and there is no clinical evidence that there is a problem with the use of different types of overlapping stents.

Disadvantages of DEB

1. DEB and DES have no significant differences in the main clinical results. Like MACE, they cause both death, cardiovascular death, ST, and MI.
2. DEB may be related to an increased incidence of TLR. DEBs have shown an efficacy comparable to that of EES in long-term clinical outcomes.
3. Furthermore, in different types of ISR (BMSISR or DESISR), DEB shows similar efficacy to DES.
4. DEB has little effect on the neoendothelialization of endothelial progenitor cells and scaffolds.
5. DEB cannot overcome the mechanical limitations of acute retraction after balloon angioplasty. Furthermore, it is not clear whether DEB can eliminate the late negative remodeling seen with uncoated balloons. The effectiveness and safety parameters of the use of DEB as an adjunctive treatment for bare metal stents (BMS) must also be determined. Other potential limitations of DEB include the variability of pharmacokinetics and dose control.

Table 1: Drug Elimination or Delivery Balloon Systems.

It is important to compare DES and DEB properly in a randomized control trial and also to compare the different types of balloons and stents available to find the absolute best treatment modality and also to have data on which type of treatment would be better for a specific group of patients.

Competing Interests: The authors declare that they have no competing interests.

Funding: None of the authors have any funding to declare.

Ethics: Given the nature of the manuscript, an IRB ethical Approval is exempted.

Acknowledgment: None.

Conflict of interest: The authors declare that they have no conflict of interest.