Background.
The advent of drug eluting stent (DES) was a milestone in the history of coronary interventions because it reduced in-stent restenosis, however, in the real world, where drug-coated stents are widely available (off lable use), their restenosis rate is not as optimistic as initially thought, and in the era of drug-coated stents, restenosis ( In the era of drug-coated stents, restenosis is still a challenging problem and, in recent years, it has been found that in-stent thrombosis, a fatal complication after drug stenting, has seriously plagued the practicing cardiovascular interventionalists. In this context, the drug coated balloon (DCB) is a new device that has emerged as a fascinating concept and is now an attractive research topic and a new hot topic in the field of coronary intervention.
DCB, a fascinating concept
The DCB, a catheter-based drug delivery device, was originally proposed by Harvey Wolinsky in 1991 to The initial animal and human studies found that the specific point of uptake of the drug by the arterial vessel wall was highly variable and that the balloon-carried drug was rapidly eluted, thus causing much clinical controversy. Until recent years, DCB became a hot research topic again in order to solve the restenosis problem. In 2004, Bruno Scheller from Germany published his animal study results on DCB to prevent restenosis after angioplasty in the journal Ciculation, and in 2006 he published his clinical study results in the New England Journal of Medicine, he was using paclitaxel-coated balloon catheter to treat 52 patients with in-stent restenosis, and the data showed that the point of vascular injury after DCB treatment may not require drug stent implantation to prevent restenosis with sustained drug release.
DCB Types
Two types of drug-coated balloons, sirolimus drug-coated balloons and paclitaxel drug-coated balloons, are available. sirolimus DCBs have a smooth surface, and the drug is applied directly to the balloon surface by a certain pressure (currently not available on the market; technicians make them on site, as shown in Figure 1, with a typical coating pressure of 2 atm, sirolimus concentration of 1%, and coating time of 5 min). 5 min). paclitaxel DCB has micro-pores on the surface where the drug is applied (as shown in Figures 2-3) and is currently available in Europe (under the trade name DIOR).
Principle of action of DCB
The mechanism of action of DCB for prevention and treatment of restenosis is similar to that of DES in that both reduce restenosis by inhibiting endothelial proliferation with the drug carried (Figure 4), both carry the drug in different ways and have different drug duration of action.
Restenosis is a chronic process, implying the need for repeated drug administration over time. Ensuring sustained drug release through local drug delivery is important for restenosis prevention. However, in the TAXUS II study, the slow release of paclitaxel-coated stents prevented endothelial hyperplasia to the same extent as moderate dose release.
The results of the current arterial study demonstrate that restenosis can be inhibited by brief exposure to drug treatment in arteries injured at the critical moment of PTCA in the identified animal model.
The DCB concept is based on Our non-stent-based, topical paclitaxel delivery inspired by the surprising observation that brief exposure of the vessel wall by contrast-carrying drugs and adequate uptake of the drug can inhibit restenosis. It was found that the addition of paclitaxel to iopromide contrast (Ultravist) for a brief holding period (3 min) almost completely inhibited vascular smooth muscle myocyte proliferation for up to 12 days. creel et al. reported that after 15 min exposure of paclitaxel plus iopromide contrast, the lipid-soluble paclitaxel entered the arterial wall dose was 20 times higher than that of heparin. As far as possible, 15 min is too long to apply to the PTCA process, but experiments have demonstrated that lipid-soluble drugs such as paclitaxel or sirolimus are rapidly taken up by the tissue. If it can indeed be demonstrated that continuous release of antiproliferative drugs is not necessary to inhibit the biological process of restenosis, then a new method of alternative drug supply during the intervention may be envisaged. The application of drugs on the catheter balloon surface is one possible option. The antiproliferative drug is retained on the balloon surface until the balloon dilates. During dilation, the drug is squeezed into the narrowed vessel wall and enough of it dissolves and penetrates the vessel wall. In the current study, treated coronary arteries were still able to measure paclitaxel concentrations in vascular tissue 40-60 min after dilation. Because the half-life of the drug is about 1 hour, the aggregation of sustained high drug concentrations is not possible.
Thus, short-term exposure to paclitaxel significantly blocks the early proliferation initiation factor, which plays a key role in subsequent endothelial formation. Importantly. Blocking this early endoplasia is sufficient to prevent restenosis from occurring.
This drug is given only during transient balloon dilatation and is rapidly lysed and disappears. Endothelial cells and their procursor cells (precursor cells) are able to migrate to the injured vessel so that vascular reendothelialization is not inhibited because these progenitor cells entering the lesion are from downstream of the lesion and have not been previously exposed to the drug distal to the lesion, thus these cells maintain normal division. To the best of our knowledge, DCB is currently the most advanced and likely alternative to stent-based local drug delivery.
Pclitaxel DCB loses only about 6% of the drug during coronary delivery, and about 80% of the drug is released during balloon dilation.
This new approach has several advantages: no need for radiation therapy, no polymer or other sustained release techniques. This technique allows drug delivery to all areas of the injured artery.
The potential clinical implications of this technique are: prevention of restenosis after angioplasty with or without stent implantation, and treatment of in-stent restenosis (as an alternative to endovascular radiation therapy or in-stent stenting).
According to current concepts and results of clinical trials, effective inhibition of restenosis requires the local administration of drugs via DES. However it is sometimes not always possible or desirable to implant a stent. Restenosis inhibition is needed in areas of vessels beyond stent coverage, between stents, in small twisted vessels and in stented restenotic vessels. Moreover, if drug supply is not consistently available from the vicinity of the original stent mesh, the stent mesh becomes more susceptible to antiproliferative drug-free vessel healing response and reendothelialization
Because of the preventive effect of DCB on restenosis, the New England Journal of Medicine published a study in 2006 on the Bruno Scheller study entitled “Treatment of In-Stent Restenosis C Back to the Future? Editional perspectives on potential treatments for restenosis demonstrate that some of the old ways of research may yield new approaches to the current persistent problem.
Indications for clinical use of DCB.
Currently DCB is mainly used in restenotic lesions, including post PTCA restenosis, post stenting restenosis, and its application in pharmacological post stenting restenosis, bifurcation lesions, and small vessel lesions is currently under investigation.
DCB application method and precautions
A DCB should not be used repeatedly in the same procedure, up to 2 times, because of drug loss. Intraoperative Rapamycin is usually applied at a low pressure of 6-8 atm, with a dilation time of 30sec-3min, to allow full release of the drug. Sometimes the dilation time can be shortened if the patient does not tolerate it. Paclitaxel DCB generally has a dilation time of not less than 1 min, with 35% of the drug released in 20 seconds for the first dilation and 35% of the drug released in 20 seconds for the second dilation. If necessary, stent implantation is required for post-dilatation entrapment.
Anti-platelet problems after DCB application
In the experience of Dr. Yu at the Bad Berka Heart Center in Germany, two antiplatelet therapy (aspirin plus clopidogrel) is usually given for 3 months after DCB (if no stent is used).
Current research topics and perspectives on DCB
Bruno Scheller, in his article “Prevention of restenosis: is angioplasty the answer?” published in Heart 2007, writes: In my personal opinion, “DCB has the potential to Improving DES has limited outcomes, for example, in patients with restenosis of coronary stents, bifurcation lesions, or other lesions where stent implantation is undesirable or impossible with DCB, which may eliminate the need for stenting. Yet drug-coated balloons (DCB) plus flexible, thin metal bare stents (BMS) are another promising new option. “Currently studies on DCB such as de novo lesions, DCB studies of bifurcation lesions, DCB studies of small vessel lesions, and DCB studies of re-DES restenosis lesions are in progress and we expect preliminary results next year, so let’s wait and see!