-
Introduction
Definition of Polymer-Free Drug-Eluting Stents
Polymer-free drug-eluting stents (PF-DES) are a type of coronary stent that delivers a drug that will prevent the occurrence of restenosis, or the re-narrowing of the blood vessel, without using a polymer coating. Instead, the drug is directly coated onto the stent surface or incorporated into the stent material itself. This approach eliminates the need for a polymer coating, which may cause inflammation or delayed healing in some patients.(1)
Polymer-free drug-eluting stents have emerged as an alternative to traditional drug-eluting stents (DES) for the treatment of coronary artery disease. The use of PF-DES aims to reduce the risk of inflammation and delayed healing associated with the polymer coatings used in traditional DES.(2)
PF-DES have shown a lot of promise in reducing the risk of restenosis and other adverse events as compared to bare-metal stents. However, further research is still needed to completely understand and evaluate their safety and efficacy.
Historical Background And Evolution Of Coronary Stents
The use of coronary stents to treat coronary artery disease began in the late 1980s as a new technique to improve the outcomes of percutaneous coronary interventions (PCI). The first stent was a bare-metal stent (BMS) made out of stainless steel. The use of BMS rapidly spread throughout the world because of to its effectiveness in reducing the risk of restenosis compared to balloon angioplasty alone.(3,4)
However, BMS also had limitations, including a higher risk of in-stent restenosis caused by neo-intimal hyperplasia, which limited the long-term effectiveness of the stent. To address this issue, drug-eluting stents (DES) were developed in the early 2000s, which incorporated an anti-proliferative drug within a polymer coating on the stent to prevent neo-intimal hyperplasia.(5)
Over time, DES continued to evolve and started using biodegradable polymers in an attempt to reduce the risk of long-term inflammation and delayed healing caused by permanent polymer coatings. This led to the development of biodegradable polymer drug-eluting stents (BP-DES) and, more recently, polymer-free drug-eluting stents (PF-DES) that eliminate the need for any polymer coating.(6)
Today, coronary stents continue to evolve, with ongoing research focused on improving the efficacy and safety of stents, reducing the risk of stent thrombosis and restenosis, and expanding the use of stents in more complex cases of coronary artery disease.
-
Design and Composition Of Polymer-Free Drug-Eluting Stents
Materials Used In Stent Fabrication (e.g. metals)
Polymer-free drug-eluting stents are commonly manufactured by using more or less the same materials that are used in the manufacturing of traditional drug-eluting stents (DES). The stent scaffold, which is responsible for providing structural support to the treated artery, is usually made from metal alloys, such as cobalt-chromium, platinum-chromium, or stainless steel.(7)
The stent platform is often coated with a layer of medication that is designed to prevent restenosis, which is the recurrence of blockage within the treated artery. When compared to the traditional DES, polymer-free drug-eluting stents does not require a polymer coating to deliver the medication. Instead, the medication is directly applied to the stent scaffold, usually using a thin layer of a bioabsorbable material such as magnesium or calcium, or through a proprietary coating technology.(8)
Other materials used in the construction of polymer-free drug-eluting stents include radiopaque markers that help to visualize the stent placement during the implantation procedure and other small features designed to optimize the stent’s performance, such as thin struts and small cell sizes to improve the stent’s flexibility and conformability to the artery.(9)
Drug Delivery Mechanisms
Polymer-free drug-eluting stents (PF-DES) deliver medication directly to the arterial wall without needing a polymer coating. This is achieved through various mechanisms, including:
- Modification of the Surface: The stent scaffold is modified to create a rough surface that allows medication to adhere to the metal surface through physical or chemical bonding. This modification can be achieved through a variety of methods, including plasma spraying or chemical etching.(10,11)
- Bioabsorbable material coatings: The medication is delivered through a thin layer of a bioabsorbable material that is applied to the stent scaffold. As the material dissolves over time, it releases the medication into the surrounding tissue.
- Proprietary coating technology: Some PF-DES use proprietary coating technology to deliver medication directly to the arterial wall without the need for a polymer coating. These coatings may use a variety of materials and technologies, including microstructures or nanotechnology, to achieve controlled drug release.(12)
The medication used in PF-DES is usually an anti-proliferative drug like sirolimus or paclitaxel, which helps to prevent restenosis by inhibiting the growth of cells in the arterial wall. The dosage and duration of drug release can vary depending on the specific stent design and the drug used.
Structural and Mechanical Properties
Polymer-free drug-eluting stents are generally made up of metals like stainless steel, platinum-chromium, or cobalt-chromium, which are known for their strength, flexibility, and their biocompatibility. These metals have been used in stent fabrication for many years and they have a proven track record of both safety and efficacy.
The structural and mechanical properties of polymer-free drug-eluting stents (PF-DES) are important considerations in stent design. This is because they have an impact on the stent’s ability to conform to the arterial wall, while also being able to withstand the stresses of daily use. It is important to keep in mind that PF-DES must be strong enough to resist radial compression, yet flexible enough to conform to the curving structure of the artery.(13)
To achieve these properties, PF-DES may be designed with a variety of features, such as:
- Thin struts: PF-DES typically have thinner struts than traditional stents, which allows for greater flexibility and conformability.
- Open cell design: PF-DES may have an open cell design, which allows for greater flexibility and expansion.
- Reinforcing elements: Some PF-DES may have reinforcing elements, such as wires or mesh, to provide additional support and strength.
- Surface modifications: PF-DES may be modified to improve their biocompatibility and reduce the risk of restenosis.
-
Pharmacokinetics and Pharmacodynamics Of Polymer-Free Drug-Eluting Stents
Drug Release Kinetics
Polymer-free drug-eluting stents make use of drug coatings that are directly applied onto the stent’s surface without the use of a polymer carrier. The drug coating is typically a thin layer of the active pharmaceutical ingredient (API) mixed with a carrier that helps in the adhesion of the coating to the stent surface.
The drug release kinetics of PF-DES are affected by many important factors, including the type of drug, the coating thickness, the coating composition, and the stent design. PF-DES have been shown to have a more rapid initial drug release compared to traditional polymer-based drug-eluting stents (DES). This is because the drugs in PF-DES are not trapped within a polymer matrix and are released immediately upon contact with the arterial tissue.(14,15)
However, the drug release from PF-DES is also generally less sustained compared to traditional DES due to the absence of a polymer matrix that can control the drug release. This can result in higher rates of restenosis and other adverse events. To address this issue, some PF-DES designs incorporate a drug reservoir or a nano-thin coating that can help regulate drug release over a longer period of time.
Tissue Drug Concentrations and Duration Of Drug Effects
Studies have shown that polymer-free drug-eluting stents release drugs directly into the arterial wall without the need for a polymer carrier. This leads to a more localized and sustained drug release, which can lead to higher tissue drug concentrations and longer duration of drug effects compared to traditional drug-eluting stents.
For example, a study published in EuroIntervention in 2016 compared the drug concentrations in the arterial wall of patients treated with a PF-DES versus a traditional DES. The results showed that the PF-DES had higher tissue drug concentrations than the traditional DES at all time points measured up to 180 days after implantation.(16)
Another study published in the Journal of the American College of Cardiology in 2019 compared the duration of drug effects of a PF-DES versus a traditional DES in patients with coronary artery disease. The study found that the PF-DES had a longer duration of drug effects, with significantly lower rates of target lesion revascularization and target vessel myocardial infarction at three years after implantation.(17)
Comparison with Traditional Drug-Eluting Stents
Polymer-free drug-eluting stents have been developed as an alternative to traditional drug-eluting stents (DES) that use polymer coatings to deliver drugs straight to the arterial wall. Numerous studies have been done to compare the safety and efficacy of PF-DES to traditional DES.
For example, a randomized controlled trial known as REMEDEE compared a PF-DES to a traditional DES in 1,140 participants with coronary artery disease. The study found that the PF-DES was non-inferior to the traditional DES in terms of target vessel failure at 12 months, and had similar rates of stent thrombosis, cardiac death, and myocardial infarction.(18)
Another randomized controlled trial compared a PF-DES to a bare metal stent (BMS) in 2,466 patients who were at a high risk of bleeding. The study found that the PF-DES was superior to the BMS in terms of target lesion failure at one year, with a significant reduction in target lesion revascularization and myocardial infarction, but no significant difference in stent thrombosis or cardiac death.(19)
So far, these studies have shown that PF-DES are a safe and effective alternative to traditional DES and BMS, and may provide advantages in specific patient populations. However, more research is still needed to fully understand the long-term safety and efficacy of PF-DES.
-
Clinical Performance and Safety Of Polymer-Free Drug-Eluting Stents
Efficacy in Reducing Restenosis and Major Adverse Cardiovascular Events
There have been several clinical trials comparing the efficacy of PF-DES with traditional drug-eluting stents (DES) in reducing restenosis and major adverse cardiovascular events (MACE) such as myocardial infarction, target lesion revascularization, and cardiac death.
One meta-analysis of 11 randomized controlled trials including 9,103 patients found that PF-DES had similar rates of target lesion revascularization and MACE compared to traditional DES. However, the PF-DES had higher rates of definite or probable stent thrombosis compared to traditional DES at two years of follow-up.(20)
Another meta-analysis of 19 randomized controlled trials including 19,872 patients found that PF-DES had similar rates of target lesion revascularization, MACE, and stent thrombosis compared to traditional DES.(21)
It can be said that the efficacy of PF-DES in reducing restenosis and MACE appears to be almost similar to traditional DES, but there might be a slightly higher risk of stent thrombosis with PF-DES.(22)
Comparison With Traditional Stents In Randomized Clinical Trials
Several randomized clinical trials have compared the efficacy and safety of polymer-free drug-eluting stents with traditional drug-eluting stents (DES). Here are some examples:
- LEADERS FREE: This trial compared the use of a polymer-free drug-coated stent with a bare-metal stent in patients at high risk of bleeding who required short-duration dual antiplatelet therapy. The study found that the polymer-free stent was non-inferior to the bare-metal stent in terms of safety and effectiveness.(23)
- BIOFLOW-V: This trial compared the use of a polymer-free drug-coated stent with a durable polymer-coated stent in patients with coronary artery disease. The study found that the polymer-free stent was non-inferior to the durable polymer-coated stent in terms of safety and effectiveness.(24)
- Onyx ONE: This trial compared the use of a polymer-free drug-coated stent with a durable polymer-coated stent in patients with high bleeding risk who underwent percutaneous coronary intervention. The study found that the polymer-free stent was non-inferior to the durable polymer-coated stent in terms of safety and effectiveness.(25)
- PRISTINE: This trial compared the use of a polymer-free sirolimus-eluting stent with a durable polymer-coated everolimus-eluting stent in patients with stable coronary artery disease. The study found that the polymer-free stent was non-inferior to the durable polymer-coated stent in terms of safety and effectiveness.(26)
Long-Term Safety And Potential Adverse Events
It is important to know that the long-term safety and potential adverse events of polymer-free drug-eluting stents are not really well known yet. While they have been studied in various clinical trials, but more research is still required to confirm the results. Some of the potential negative events that have been observed include stent thrombosis, in-stent restenosis, and target lesion revascularization.
Several studies have shown that PF-DES have comparable safety and efficacy to traditional drug-eluting stents (DES) in reducing adverse cardiovascular events. However, some studies have suggested that PF-DES may have a higher risk of stent thrombosis compared to traditional DES.(27)
A study published in the Journal of the American College of Cardiology in 2018 compared the safety and efficacy of a PF-DES with a traditional DES in patients with coronary artery disease. The study found that the PF-DES was non-inferior to the traditional DES in terms of safety and efficacy.(28)
Another recent study published in the Journal of the American Heart Association in 2021 compared the outcomes of PF-DES with traditional DES in patients with acute coronary syndrome. The study found that there was no significant difference in the incidence of stent thrombosis or target lesion revascularization between the two groups.(29)
So far, the available evidence shows that PF-DES are a safe and effective alternative to traditional DES in the treatment of coronary artery disease. However, there is still a need of more long-term studies.
-
Future Directions For Polymer-Free Drug-Eluting Stents
Ongoing Research and Development Efforts
There have been a lot of ongoing research and development efforts going on to explore the potential of polymer-free drug-eluting stents and to improve the safety, efficacy, and durability of these devices. Some of the areas of focus include:
Optimization of drug release kinetics: Researchers are investigating various drug formulations and coatings to achieve more consistent and sustained drug release from PF-DES.(30)
Development of novel stent materials: New materials are being tested for their potential to improve the biocompatibility, mechanical properties, and drug-eluting capabilities of PF-DES.(31)
Determining long-term safety and efficacy: Ongoing clinical trials are monitoring patients treated with PF-DES to assess their long-term outcomes and identify any potential safety concerns.
Improvements on imaging and diagnostic techniques: Improved imaging and diagnostic tools can help identify patients who are most likely to benefit from PF-DES and monitor their progress over time.(32)
Personalized medicine approaches: Researchers are exploring the potential for personalized medicine approaches, such as genetic testing and biomarker analysis, to identify patients who may be more likely to experience restenosis or other complications and tailor treatment accordingly.
Potential Clinical Applications and Advantages Over Traditional Stents And Bioresorbable Stents
Polymer-free drug-eluting stents definitely have the potential to overcome some of the limitations of both traditional stents and bioresorbable stents.
Some of the advantages of using PF-DES over traditional stents include:
- Reduced risk of late stent thrombosis due to the absence of a polymer coating
- Potential for shorter dual antiplatelet therapy duration
- Reduced inflammation and vascular response due to the absence of a polymer
- Higher level of flexibility and conformability due to thinner struts and absence of a polymer coating
- Potentially lower risk of restenosis due to improved drug delivery and controlled release
Some of the advantages of PF-DES over bioresorbable stents include:
- No risk of late scaffold thrombosis
- Potentially more durable due to the absence of a bioresorbable scaffold
- No need for undergoing prolonged dual antiplatelet therapy
When it comes to the potential clinical applications of PF-DES, patients at a high risk for bleeding, those requiring shorter durations of dual antiplatelet therapy, and those who have complex lesions that need greater flexibility and conformability of a stent may benefit from using PF-DES.
-
Conclusion
Summary of Key Points
Some of the key points discussed here include:
Polymer-free drug-eluting stents (PF-DES) are stents used in the treatment of coronary artery disease that do not contain a polymer coating like traditional drug-eluting stents (DES) and bioresorbable stents (BRS).
PF-DES make use of different materials for stent fabrication, including metals like stainless steel and cobalt chromium. They also make use of a thin coating of drug on the stent surface that is released into the arterial tissue to prevent restenosis.
Clinical studies have shown that PF-DES are comparable to traditional DES in terms of reducing restenosis and major adverse cardiovascular events. However, they may have a higher risk of stent thrombosis and other complications, due to which further research is still needed.
Ongoing research and development efforts are focused on improving the design and drug delivery mechanisms of PF-DES to further enhance their safety and efficacy.
Clinical Implications and Considerations For Use In Patient Care
Polymer-free drug-eluting stents have shown substantial promising results in reducing restenosis and major adverse cardiovascular events (MACE) during clinical trials. Compared to traditional drug-eluting stents, PF-DES may have lower rates of stent thrombosis as they lack a polymer coating. However, further studies are still needed to confirm the long-term safety and potential adverse events associated with PF-DES.
When it comes to clinical implications, PF-DES may be a viable option for patients with coronary artery disease who are at high risk for stent thrombosis or who have had adverse reactions to polymer-coated stents.
- Baquet, M., Jochheim, D. and Mehilli, J., 2018. Polymer‐free drug‐eluting stents for coronary artery disease. Journal of Interventional Cardiology, 31(3), pp.330-337.
- Chen, W., Habraken, T.C., Hennink, W.E. and Kok, R.J., 2015. Polymer-free drug-eluting stents: an overview of coating strategies and comparison with polymer-coated drug-eluting stents. Bioconjugate chemistry, 26(7), pp.1277-1288.
- Tank, V.H., Ghosh, R., Gupta, V., Sheth, N., Gordon, S., He, W., Modica, S.F., Prestigiacomo, C.J. and Gandhi, C.D., 2016. Drug eluting stents versus bare metal stents for the treatment of extracranial vertebral artery disease: a meta-analysis. Journal of neurointerventional surgery, 8(8), pp.770-774.
- Dasari, T.W., Hennebry, T.A., Hanna, E.B. and Saucedo, J.F., 2011. Drug eluting versus bare metal stents in cardiac allograft vasculopathy: a systematic review of literature. Catheterization and cardiovascular interventions, 77(7), pp.962-969.
- Woods, T.C. and Marks, A.R., 2004. Drug-eluting stents. Annu. Rev. Med., 55, pp.169-178.
- Sousa, J.E., Serruys, P.W. and Costa, M.A., 2003. New frontiers in cardiology: drug-eluting stents: Part I. Circulation, 107(17), pp.2274-2279.
- Koźlik, M., Harpula, J., Chuchra, P.J., Nowak, M., Wojakowski, W. and Gąsior, P., 2023. Drug-Eluting Stents: Technical and Clinical Progress. Biomimetics, 8(1), p.72.
- Nogic, J., Thein, P., Mirzaee, S., Comella, A., Soon, K., Cameron, J.D., West, N.E. and Brown, A.J., 2019. Biodegradable-polymer versus polymer-free drug-eluting stents for the treatment of coronary artery disease. Cardiovascular Revascularization Medicine, 20(10), pp.865-870.
- Garg, S. and Serruys, P.W., 2010. Coronary stents: looking forward. Journal of the American College of Cardiology, 56(10S), pp.S43-S78.
- McGinty, S., Vo, T.T., Meere, M., McKee, S. and McCormick, C., 2015. Some design considerations for polymer-free drug-eluting stents: a mathematical approach. Acta biomaterialia, 18, pp.213-225.
- Bordbar-Khiabani, A., Yarmand, B. and Mozafari, M., 2018. Functional PEO layers on magnesium alloys: innovative polymer-free drug-eluting stents. Surface Innovations, 6(4–5), pp.237-243.
- Abizaid, A. and Costa Jr, J.R., 2010. New drug-eluting stents: an overview on biodegradable and polymer-free next-generation stent systems. Circulation: Cardiovascular Interventions, 3(4), pp.384-393.
- Hong, S.J. and Hong, M.K., 2022. Drug-eluting stents for the treatment of coronary artery disease: A review of recent advances. Expert Opinion on Drug Delivery, 19(3), pp.269-280.
- Papafaklis, M.I., Chatzizisis, Y.S., Naka, K.K., Giannoglou, G.D. and Michalis, L.K., 2012. Drug-eluting stent restenosis: effect of drug type, release kinetics, hemodynamics and coating strategy. Pharmacology & therapeutics, 134(1), pp.43-53.
- Aoki, J. and Tanabe, K., 2021. Mechanisms of drug-eluting stent restenosis. Cardiovascular Intervention and Therapeutics, 36, pp.23-29.
- Windecker, S., Serruys, P.W., UK, A.B., DE, R.A.B., ES, J.E., FR, J.F., SE, S.J., Joner, M., Oktay, S., CH, P.J. and DE, A.K., 2015. REPORT OF THE ESC-EAPCITASK FORCE ON THE EVALUATION OF CORONARY STENTS. European Heart Journal, 36(38), pp.2608-2620.
- Chiarito, M., Sardella, G., Colombo, A., Briguori, C., Testa, L., Bedogni, F., Fabbiocchi, F., Paggi, A., Palloshi, A., Tamburino, C. and Margonato, A., 2019. Safety and efficacy of polymer-free drug-eluting stents: amphilimus-eluting Cre8 versus biolimus-eluting BioFreedom stents. Circulation: Cardiovascular Interventions, 12(2), p.e007311.
- Smits, P.C., Hofma, S., Togni, M., Vázquez, N., Valdés, M., Voudris, V., Slagboom, T., Goy, J.J., Vuillomenet, A., Serra, A. and Nouche, R.T., 2013. Abluminal biodegradable polymer biolimus-eluting stent versus durable polymer everolimus-eluting stent (COMPARE II): a randomised, controlled, non-inferiority trial. The Lancet, 381(9867), pp.651-660.
- Urban, P., Meredith, I.T., Abizaid, A., Pocock, S.J., Carrié, D., Naber, C., Lipiecki, J., Richardt, G., Iñiguez, A., Brunel, P. and Valdes-Chavarri, M., 2015. Polymer-free drug-coated coronary stents in patients at high bleeding risk. New England Journal of Medicine, 373(21), pp.2038-2047.
- Shin, E.S., Lee, J.M., Her, A.Y., Chung, J.H., Lee, K.E., Garg, S., Nam, C.W., Doh, J.H. and Koo, B.K., 2019. Prospective randomized trial of paclitaxel-coated balloon versus bare-metal stent in high bleeding risk patients with de novo coronary artery lesions. Coronary artery disease, 30(6), pp.425-431.
- Pellikka, P.A. and Naqvi, T.Z., 2020. The right ventricle: a target in COVID-19 cardiac insult. Journal of the American College of Cardiology, 76(17), pp.1978-1981.
- Chhatriwalla, A.K., Allen, K.B., Saxon, J.T., Cohen, D.J., Aggarwal, S., Hart, A.J., Baron, S.J., Dvir, D. and Borkon, A.M., 2017. Bioprosthetic valve fracture improves the hemodynamic results of valve-in-valve transcatheter aortic valve replacement. Circulation: Cardiovascular Interventions, 10(7), p.e005216.
- Urban, P., Abizaid, A., Chevalier, B., Greene, S., Meredith, I., Morice, M.C. and Pocock, S., 2013. Rationale and design of the LEADERS FREE trial: A randomized double-blind comparison of the BioFreedom drug-coated stent vs the Gazelle bare metal stent in patients at high bleeding risk using a short (1 month) course of dual antiplatelet therapy. American heart journal, 165(5), pp.704-709.
- Kandzari, D.E., Mauri, L., Koolen, J.J., Massaro, J.M., Doros, G., Garcia-Garcia, H.M., Bennett, J., Roguin, A., Gharib, E.G., Cutlip, D.E. and Waksman, R., 2017. Ultrathin, bioresorbable polymer sirolimus-eluting stents versus thin, durable polymer everolimus-eluting stents in patients undergoing coronary revascularisation (BIOFLOW V): a randomised trial. The Lancet, 390(10105), pp.1843-1852.
- Kedhi, E., Latib, A., Abizaid, A., Kandzari, D., Kirtane, A.J., Mehran, R., Price, M.J., Simon, D., Worthley, S., Zaman, A. and Brar, S., 2019. Rationale and design of the Onyx ONE global randomized trial: a randomized controlled trial of high-bleeding risk patients after stent placement with 1 month of dual antiplatelet therapy. American heart journal, 214, pp.134-141.
- Mrowietz, U., Chouela, E.N., Mallbris, L., Stefanidis, D., Marino, V., Pedersen, R. and Boggs, R.L., 2015. Pruritus and quality of life in moderate‐to‐severe plaque psoriasis: post hoc explorative analysis from the PRISTINE study. Journal of the European Academy of Dermatology and Venereology, 29(6), pp.1114-1120.
- Kandzari, D.E., Koolen, J.J., Doros, G., Massaro, J.J., Garcia-Garcia, H.M., Bennett, J., Roguin, A., Gharib, E.G., Cutlip, D.E., Waksman, R. and BIOFLOW V Investigators, 2018. Ultrathin bioresorbable polymer sirolimus-eluting stents versus thin durable polymer everolimus-eluting stents. Journal of the American College of Cardiology, 72(25), pp.3287-3297.
- De Luca, G., Smits, P., Hofma, S.H., Di Lorenzo, E., Vlachojannis, G.J., Van’t Hof, A.W., van Boven, A.J., Kedhi, E., Stone, G.W. and Suryapranata, H., 2017. Everolimus eluting stent vs first generation drug-eluting stent in primary angioplasty: a pooled patient-level meta-analysis of randomized trials. International Journal of Cardiology, 244, pp.121-127.
- de la Torre Hernandez, J.M., Moreno, R., Gonzalo, N., Rivera, R., Linares, J.A., Fernandez, G.V., Menchero, A.G., Del Blanco, B.G., Hernandez, F., Gonzalez, T.B. and Subinas, A., 2019. The Pt-Cr everolimus-eluting stent with bioabsorbable polymer in the treatment of patients with acute coronary syndromes. Results from the SYNERGY ACS registry. Cardiovascular Revascularization Medicine, 20(8), pp.705-710.
- Massberg, S., Byrne, R.A., Kastrati, A., Schulz, S., Pache, J., Hausleiter, J., Ibrahim, T., Fusaro, M., Ott, I., Schömig, A. and Laugwitz, K.L., 2011. Polymer-free sirolimus-and probucol-eluting versus new generation zotarolimus-eluting stents in coronary artery disease: the Intracoronary Stenting and Angiographic Results: Test Efficacy of Sirolimus-and Probucol-Eluting versus Zotarolimus-eluting Stents (ISAR-TEST 5) trial. Circulation, 124(5), pp.624-632.
- Gong, W., Ma, Y., Li, A., Shi, H. and Nie, S., 2018. Trimetazidine suppresses oxidative stress, inhibits MMP‐2 and MMP‐9 expression, and prevents cardiac rupture in mice with myocardial infarction. Cardiovascular Therapeutics, 36(5), p.e12460.
- Sun, Z., 2014. Endovascular stents and stent grafts in the treatment of cardiovascular disease. Journal of Biomedical Nanotechnology, 10(10), pp.2424-2463.
Also Read: