The post-2003 era of drug-eluting stents (DES) has become a new milestone in coronary interventions, as its excellent clinical efficacy has brought great encouragement to clinicians and a boon to patients. The current development of DES is at an important turning point, where its efficacy is evaluated not only in inhibiting in-stent restenosis, but also in reducing adverse cardiovascular endpoints in patients. The real demand from clinicians for stents is for both immediate effectiveness and long-term safety. Immediate effectiveness includes smooth delivery of the stent to the lesion, dilatation of the lesion, effective inhibition of restenosis and reduction of complications. Long-term safety includes no clinical symptoms after the procedure, no long-term thrombosis, no chasing and reduced drug costs. With the continuous development of new technologies, various new drug stents that are safer, more effective and more desirable are emerging. The ideal coronary stent should have several features. First, the stent should serve as a mechanical platform to provide physical support to avoid acute retraction and to compress and close large intimal tears. Furthermore, the stent should be deliverable and visible. Second, the stent should allow for complete endothelialization to prevent in-stent thrombosis, while allowing for a reduced level of vascular healing response (leading to proliferation of new endothelium). The use of biocompatible and biodegradable polymer coatings in next-generation DES has become a consensus, and carrier-free drug stents are another promising approach. Research on completely degradable stents has made great progress and has been gradually tried in the clinic. I. Design and improvement of drug carriers In order to achieve controlled drug release, the first generation DES used non-degradable polymers – they existed long after drug release. The non-degradable polymers may have contributed to stent thrombosis. The new generation DES uses biodegradable polymer coatings, which means that as the drug is released from the DES after stent placement, the polymer is partially or completely broken down. the most commonly used degradable polymers are PLA and PLGA, both of which can be metabolized to water and carbon dioxide, leaving only a bare metal stent platform locally after complete drug release. Coated DES achieve the ability to control the release of the drug and ensure the effectiveness of DES. Studies have shown that the advantages of biodegradable polymers as drug-controlled release carriers are: good biocompatibility, especially hemocompatibility; temporary support for narrow lumen without long-term complications. However, clinical studies have found that the incidence of late thrombosis in DES is slightly higher than that in bare metal stents, and the residual Polymer after drug release is complete may be one of the main triggers for increased late thrombosis and its adverse tissue reactions. Carrier-free DES have been used in the clinic and have achieved good clinical results. In order to meet the clinical challenges posed by the first generation DES, the newly developed intravascular carrier-free drug-eluting stent from Beijing LOPE Medical Devices Co. This carrier-free drug stent avoids both permanent irritation of the vessel wall by non-degradable polymers, which affects endothelialization, and the adverse effects of degradable polymers prior to degradation and potential side effects during degradation. Multicenter clinical trials have confirmed the effectiveness of this stent in reducing late lumen loss. The results of our study showed that the incidence of MACE was relatively low in more than 250 cases of Nano stent application, after 2 years of observation. Further studies are needed for long-term effectiveness and safety. II. Improvement of the contained drugs Drugs are the core of drug stents. The first generation of drug stents mainly used anti-proliferative drugs, commonly rapamycin and paclitaxel and their derivatives, whose main function is to inhibit the growth of new endothelium in order to prevent restenosis, but it does not target the lesion itself, which is easy to form late thrombosis. Recently some novel drugs and drug combinations are being developed and tested. Tacrolimus: is another macrolide immunosuppressant approved for post-transplant anti-rejection use. Tacrolimus arrests cells in the G0 phase, so cells are unable to replicate and proliferate, but does not affect cell function. In addition, the effect of tacrolimus is cell-selective, apparently on SMCs but not on endothelial cells, and unlike mTOR inhibitors and paclitaxel, tacrolimus does not increase TF expression. preclinical studies by Grube et al. and Kollum et al. demonstrated that tacrolimus is safe as a drug coating for stents and significantly reduces restenosis. Currently, tacrolimus stents are used in clinical practice. Zotamox The chemical structure of zotamox contains a tetrazole ring, which makes the drug more lipophilic and less water-soluble. It is believed that zotamox can make the drug enter the tissue (vessel wall) more easily and reduce the amount entering the blood circulation, so that it can better inhibit the excessive proliferation of new endothelium and prevent restenosis in the stent. Everolimus belongs to a new class of immunosuppressants that can inhibit smooth muscle cell proliferation and prevent intimal thickening and atherosclerosis. When everolimus is used as a stent-coating drug, its entry into the vessel wall has a longer duration of inhibition of intimal hyperplasia. The prospect of the drug is that a new drug will be developed to inhibit neointimal hyperplasia and promote vascular endothelialization in an asymmetric dual drug-coated stent, i.e., an antiproliferative drug such as rapamycin can be coated on the outer surface of the stent in contact with the vessel wall, while a drug that can antithrombotic and promote endothelialization can be sprayed on the luminal surface of the stent in contact with the blood. In this way, the drug stent can effectively reduce the occurrence of late thrombosis while reducing restenosis. Improvement of stent platform The stent platform determines the support, compliance and permeability of the stent, which directly affects the restenosis, thrombosis rate and the smoothness of surgical operation in the stent. As a carrier stent, conventional coronary stents have the inevitable disadvantages of “permanent foreign body implantation” and limitations in vascular diastolicity. The optimal design concept for the new generation of stents is that they mechanically support the vessel for a period of time after the intervention and prevent restenosis with the help of eluting drugs. After that, the stent is slowly degraded and completely absorbed by the tissues, and the vascular structure as well as the diastolic function is completely restored to its natural state. Therefore, the occurrence of late/very late stent thrombosis should be reduced, so that long-term antiplatelet drug therapy is not necessary. In addition, because the stent can be absorbed, local vascular diastolic motion is restored without increasing the difficulty of re-PCI or surgical revascularization. This is what has been called the fourth revolution in coronary intervention – the fully biodegradable stent. Currently, several companies are developing fully biodegradable stents, such as Abbott (BVS), Igaki Medical (Igaki-Tamai), Biotronik (AMS), REVA Medical (REVA), Johnson & Johnson, Orbus Neich, ART, etc. Abbott BVS (Bioresorbable Vessel Scaffold) has started clinical studies and achieved promising results. This fully degradable stent, which completely degrades into water and carbon dioxide within two years, has become a new and interesting development in the fourth revolution of coronary intervention. 1.Polymer type biodegradable stent The representative stent is biodegradable everolimus drug-eluting polylactic acid stent (bioabsorbable everolimus-eluting stent (BVS)), poly lactide acid (Poly Lactide Acid) as bioabsorbable stent material, everolimus (Zotarolimus) has anti-proliferative effect. Poly Lactide Acid is a polymer with good biocompatibility and degradability, high strength and easy processing and molding.BVS stents are designed to restore blood flow and can gradually degrade to water and carbon dioxide during 2 years of implantation.ABSORB study aims to verify the effectiveness and safety of BVS. The current study showed only 1 MACE (major adverse cardiovascular event) at 3 years of follow-up with the BVS stent and no stent thrombotic events, and the BVS continues to have good efficacy. late lumen loss at 6 months was similar to that of metallic drug stents; the 1-year follow-up showed an ischemia-driven MACE rate of 6.9%. This biodegradable stent technology will provide unique physiologic benefits to patients by allowing for restoration of vessel integrity and function to its natural state. Despite acute stent retraction of up to 22% with PLLA degradable stents, the clinical trial results were encouraging, with a 6-month target lesion revascularization rate of only 10.5%. A PLLA drug-eluting stent carrying everolimus has recently completed clinical evaluation with promising results. This stent showed good mechanical performance: acute stent retraction was similar to that of the cobalt-chromium alloy everolimus-eluting stent (6.9% vs. 4.9%). This stent does not have X-ray visualization, but a platinum metal marker at each end of the stent ensures its identifiability during CAG or noninvasive coronary imaging. 2.Biodegradable iron stent Iron is an important element in human body and has various physiological functions. The reliability and safety of biodegradable iron stent (containing >99.8% iron) was tested for the first time by Peuster et al. The stent was implanted in the descending aorta of 16 New Zealand white rabbits and showed good mechanical performance, no thromboembolic events, and no MACE during the 6-18 month follow-up period. histopathology demonstrated no significant inflammatory response or hyperplasia of new tissue and no toxic side effects. For the evaluation of biodegradable iron stent is still to be supported by more trial data. Action 3, biodegradable magnesium-alloy stent (biodegradable magnesium-alloy stent) magnesium alloy has ideal mechanical support, good biocompatibility, and easy to degrade, degradation products involved in metabolism. The application of magnesium alloys to make biodegradable stents has become a recent research hotspot. A large number of animal experiments showed complete and rapid endothelialization, a small amount of endothelial hyperplasia and low inflammatory response after implantation of biodegradable magnesium stents.Raimund, Erbel et al. reported the world’s first prospective, non-randomized multicenter clinical trial on biodegradable magnesium alloy stents, PROGRESS-AMS, in 63 patients with primary single-branch lesions, lesion length 10-15 mm in length and 3.0-3.5 mm in diameter, were successfully implanted with biodegradable magnesium stents. The results showed good mechanical support of the biodegradable magnesium stent with no infarction, subacute or late thrombosis, or cardiac death during the follow-up period. Increasing clinical trials have shown that the complete biodegradability, good biocompatibility, and effective support of biodegradable coronary stents have heralded the future direction of stent development. In conclusion, the era of innovation in stents that minimize complications is approaching and will bring tremendous benefits to patients with coronary heart disease.