Year : 2021 | Volume
: 11 | Issue : 1 | Page : 1--4
The relevance of bare-metal stent in the therapy of coronary artery disease in 2020
Department of Cardiology, Vivekananda Institute of Medical Sciences, Kolkata, West Bengal, India
Dr. Saumitra Ray
99/5/C, Ballygunge Place, Kolkata - 700 019, West Bengal
First percutaneous transluminal coronary angioplasty (PTCA) using an expandable balloon was performed by Andreas Gruentzig in 1977. Since then, the process has seen exponential development. Stent deployment was the most important milestone in this journey. An original stent made of metals or metal alloys was called a bare-metal stent (BMS). They ruled the roost for more than a decade when stents coated with antiproliferative drug impregnated polymers, called drug-eluting stent came and became the tool of choice in almost all clinical scenarios of PTCA. However, still today, BMS has got a small but significant place in the cardiac catheter laboratory. The relevance of BMS in the therapy of coronary artery disease in today's world is reviewed in this article.
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Ray S. The relevance of bare-metal stent in the therapy of coronary artery disease in 2020.J Indian coll cardiol 2021;11:1-4
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Ray S. The relevance of bare-metal stent in the therapy of coronary artery disease in 2020. J Indian coll cardiol [serial online] 2021 [cited 2021 Apr 12 ];11:1-4
Available from: https://www.joicc.org/text.asp?2021/11/1/1/309620
When Andreas Gruentzig did the first percutaneous transluminal coronary angioplasty (PTCA) with a balloon in coronary artery on an awake patient on September 16, 1977, in Zurich, a new horizon of endovascular therapy opened up. Although this technique was hugely acclaimed on both sides of the Atlantic, its Achilles heel became apparent soon in the form of acute coronary dissection and coronary thrombosis, with bailout surgery being a common occurrence.
To circumvent these problems, three approaches were explored simultaneously, namely improvement of endovascular gadgets, improvement of the delivery technique, and development of pharmacotherapy.
To address the first issue, the concept of stent emerged. Endovascular stent was designed by Palmaz by making metal wire scaffolding around a pencil with soldering of the joints. Experimented successfully in peripheral arteries initially, they were deployed in the coronary arteries and saphenous venous grafts. With rapid technological advancement and successful application of bioengineering in this field, soon, the bare-metal stent (BMS) became a rage with the cardiologists. With the backup of highly successful clinical trials, BMS seemed to solve all the problems incurred by balloon PTCA.
However, soon enough, it became apparent that though BMS did take care of coronary dissection and acute vessel wall recoil during PTCA, there were still the problems of acute stent thrombosis (AST) and a new phenomenon of in-stent restenosis (ISR) due to overgrowth of intima–media cells in the treated coronary segment as a result of tissue injury and remodeling of the coronary arteries.
The AST issue was primarily taken up by the pharmacotherapists by developing and experimenting with newer antiplatelet and antithrombotic medications. The ISR part was the headache of the stent manufacturers. A novel concept emerged to counter the overgrowth of the endothelial and smooth muscle cells in the wall of the injured coronary artery by interfering with the cell growth cycle using anticancer drugs incorporated in the metal struts by coating them with beads of polymer impregnated with the drug.
Initial studies demonstrated thumping success with this drug-eluting stent (DES) and the problems of PTCA seemed to be permanently settled at last. However, as time passed, it started revealing that though the rate of AST remained the same as with BMS, late and very late stent thromboses were new phenomena associated with DES. The drug might have been working too strongly or too long to prevent the natural and optimal healing of the endocardium or there might be a reaction to the polymer material.
Hence, a new endeavor started to address these issues using newer and safer drugs and newer and short-lasting polymers, making stent struts as less injurious as possible and even developing bioresorbable vascular scaffold bioserorbable vascular scaffold (BVS) which vanishes from the system after a few weeks.
Thus, it becomes apparent that in the pursuit of an endovascular system that maintains efficacy, but without the complications, new stents will keep on emerging. In this ever-changing scenario, the position of the older members of the stent family, for example, BMS and first-generation DES, needs to be redefined. BMS is still relevant in a small but significant subset of patients. This review is to explore the status of BMS in the therapy of coronary artery disease (CAD) in the year 2020.
Resume of Development of Coronary Stents
Dotter and Judkins did the first successful peripheral angioplasty using a catheter in 1964. Andreas Gruentzig from Germany learned the technique from Charles Dotter in the US. On return to Germany, he wanted to expand the procedure but faced bureaucratic resistance from the German authority, so he migrated to Switzerland, and it took more than a decade to replicate the procedure in the coronary artery when Gruentzig performed the first PTCA in 1977 on an awake patient. There was an instant acceptance of the technique in Europe, the USA, and Australia. Gruentzig used to conduct a large number of workshops to train doctors on the technique.
The basic mechanism was to compress the lipid plaque with balloon inflation and sometimes to rupture the plaque to gain vessel diameter. However, acute elastic recoil and dissection of the vessel wall were not infrequent, necessitating emergency surgery. Furthermore, as the endothelium was denuded and highly thrombogenic subendocardial milieu was exposed to blood, AST was not uncommon. Moreover, in about 30'–40' cases, there was restenosis due to neointimal hyperplasia and chronic negative remodeling of the vessel wall within 6–9 months.
The concept of coronary stent came to circumvent the problems of restenosis and late recoil associated with PTCA. In the same year of 1986, both Puel and Sigwart developed self-expanding coronary stent, the Wallstent, in Switzerland. The first balloon-expandable stent was designed in the USA in 1988 by Palmaz and Schatz. These BMS were made of stainless steel with the attendant problems of excessive thickness and less flexibility. In 1993, two major trials, namely Benestent and stress, were published showing a great benefit of these stents over balloon PTCA in terms of abrupt vessel closure and late restenosis.
The associated problems of BMS emerged in the form of AST and still unacceptable rates of late ISR. The former was addressed using antiplatelets and anticoagulants but at the cost of increasing bleeding complications. Furthermore, using intravascular ultrasound, it was found that under deployment of the stent was a major cause of AST. Using higher pressure during stent deployment and using dual antiplatelet therapy (DAPT, aspirin with ticlopidine, and later on, clopidogrel) partly reduced the incidence of AST. At the same time, stainless steel was replaced by alloys like cobalt–chromium and platinum–chromium to give the BMS thinner struts with increased flexibility, increased radial strength, and good visibility. With all these strategies, still, the ISR rate was 15'–30' in the long-term follow-up.
As neointimal hyperplasia and smooth muscle cell proliferation were identified as the most important causes of ISR, the idea came to block this cell growth by delivering antiproliferative drugs locally using the same stent scaffold as the drug delivery tool as well. Souse in Brazil implanted the first DES in 1999. The two initial DESs were CYPHER using sirolimus and TAXUS using paclitaxel. Both were developed in the USA. Both these stents were stainless steel in nature and had a strut thickness of more than 130μ. Many trials confirmed a significant reduction of rates of ISR and target vessel revascularization (TVR)/target lesion revascularization (TLR) compared to BMS.
However, the early enthusiasm was dampened a bit when in 2006 two studies revealed that DES was associated with more late and very late stent thrombosis.,
The possible explanations forwarded were delayed endothelialization due to antiproliferative drugs and allergic reaction to the polymers. Hence, the second-generation DES was designed using alloy metals to give thinner struts with more flexibility, using less allergen polymers and developing newer drugs and drug delivery mechanisms. These second-generation DES became the stent of choice. The incidence of late and very late ST came down to below 1' in 5 years but still necessitated at least 1 year of DAPT. Further research was focused on developing biodegradable polymers (stents behaving as DES in the early phase and then becomes essentially a BMS) and polymer-free stents, even using nanoparticles to deliver the drug.
A potentially fourth-generation stent is a bioresorbable vascular system (BVS). They are made of magnesium or iron alloy. They give initial mechanical support to the vessel wall to prevent acute closure by immediate restenosis or vascular recoil and deliver the drug. However, after 1 year, the whole stent system gets absorbed in the body, thus removing any potential nidus for the complication, allowing normal physiological vasomotion, and permitting graft insertion, if needed. However, they need further studies.
Data on Comparison of Bare-Metal Stent and Drug-Eluting Stent
Most of the advantages of DES over BMS depend on the continuation of DAPT for a longer time. The exact duration of DAPT (or, sometimes, antiplatelet with anticoagulant) is subject to intense research and is ever changing over the last one decade. Hence, the question remains if BMS has still placed in the cardiac catheter laboratory (CCL). The fundamental advantage of BMS over DES is the need for less intense and less prolonged antithrombotic use, and the fundamental disadvantage is more chance of ISR.
Studies have been done to compare BMS and DES in different clinical setups.
In large diameter arteries, it is intuitive that ISR will be less relevant. A study was published in 2007 comparing BMS with DES in coronary arteries with a diameter 3.5 mm or more in 320 patients. At 1 year, the rates of death, Q-wave myocardial infarct (MI), TLR, and major adverse cardiovascular event were the same in both arms with numerically more death and MI in the DES arm. There was no late thrombosis in either arm.
In 2013, a meta-analysis was published comparing the outcome of BMS with the first-generation DES in diabetic subjects undergoing primary percutaneous coronary intervention (PPCI). At 6-year follow-up, no difference was observed between the two arms in terms of mortality, re-infarction, or stent thrombosis. However, TVR was significantly in favor of DES.
In the NORSTENT clinical trial published from Norway in 2016, 9013 patients of wide clinical scenarios were equally divided to receive BMS and DES. Approximately 26' of the patients in each group had ST-segment elevation myocardial infarction (STEMI), 31' had non-STEMI, 12' had unstable angina, and 29' had stable angina. All the percentages were almost equal in the two groups. Multivessel disease was present in 40' of the patients in each group. Throughout the study period of 7 years, there was absolutely no difference between the two groups in terms of the composite primary outcome of death from any cause and nonfatal MI and also separately for all-cause mortality. Definite stent thrombosis rates were also almost the same (P = 0.05). However, repeat revascularization rate (both percutaneous coronary intervention [PCI] and coronary artery bypass grafting [CABG]) was much higher with BMS, and the difference was obvious from year 1. In terms of physical limitations, angina stability, angina frequency, treatment satisfaction, and quality of life, both the arms were exactly the same throughout the study duration.
In a systematic review in 2017, comparing BMS with second-generation DES, it was again clearly revealed that there was no mortality advantage even with second-generation DES, but TVR was the only parameter which was significantly less with DES. Up to 1 year and also beyond that, DES, especially cobalt–chromium everolimus stent, had some benefits for MI. The higher cost of DES was compensated by the lower rate of TVR, especially in patients with a high risk of ISR. The high-risk factors included were vessel diameter <3 mm, lesion length 20 mm or more, diabetic patients, and a history of PCI or CABG.
In an interesting analysis by Schmidt et al. in 2018, BMS and DES made of the same platforms were compared. Many manufacturers who had made BMS kept the basic metal scaffolding the same while developing DES. Examples include Pro-Kinetic Energy and Orsiro; MULTI-LINK and XIENCE Xpedition; REBEL Monorail and Promus PREMIER; Integrity and Resolute Integrity; and Kaname and Ultimaster. Of the five pairs of stents, two had lower crimped stent profile with the BMS variety compared to their corresponding DES. Distal force and crossability were higher with DES varieties but again not for all the pairs. Bending stiffness also showed variable results. Side branch accessibility was better with DES but in two pairs only. This study revealed that some differences between BMS and DES exist in terms of mechanical properties, but those differences are product dependent and in general, not group specific. In some difficult cases, mechanical properties of stent become crucial though in the majority of cases that is irrelevant. Overall, BMS came out as slightly better compared to DES with respect to profile, crossability, and bending stiffness of the crimped stent on its delivery system.
Position of Bare-Metal Stent in Present Era
Thus, it is apparent that BMS (as compared to DES) has the following advantages:
Less late and very late STNeed a lesser duration of DAPTLess costly (in India, the average cost is INR 8000, as compared to INR 32,000 for DES).
The major disadvantages are:
More ISR, necessitating more TLR/TVRNot designed for bifurcation lesions, chronic total occlusion, or complicated lesionsNot suitable for small arteries (especially below 3.0 mm diameter), left main disease, or saphenous venous graft lesion.
Real-world data from 31 countries of Europe and Asia were published by Morice et al. in 2013 looking into the contemporary use of BMS. In 744 consecutive patients who received BMS, it was found that in 32.4' cases, the indication was large-vessel diameter. Other causes included STEMI (17.7'), advanced age (12.4'), need of oral anticoagulation therapy (11.3'), increased bleeding risk, cancer or anemia (9.5'), financial (9.4'), planned noncardiac surgery within a year (5.5'), and anticipated poor DAPT compliance (1.7'). This essentially captured all the major reasons for choosing a BMS in the era of DES.
However, over the next 7 years after the publication of these data, many aspects have changed. With aggressive antithrombotic therapy, acute ST is less of a problem even with DES in the STEMI setup. Rather, DES is now the default stent for PPCI. This is also to be understood that acute ST is not dependent on the type of stent as the endothelium remains denuded after injury by stent irrespective of whether the drug is eluting or not. It is after 4–6 weeks, it matters when BMS allows complete healing of the endocardium, but DES does not.
Furthermore, with improved design of stents as discussed earlier, the need for prolonged DAPT has decreased considerably with some newer studies recommending even only 1 month of DAPT after DES use.
However, patients who are already bleeding from some sources during the PTCA or who need an urgent major surgery in the near future, BMS are still relevant, especially for arteries larger than 3.5 mm in diameter. Furthermore, DES is not available in more than 5 mm in diameter. So for exceptionally large artery or ectatic artery, BMS is still needed. In case of per procedure coronary rupture, the lifesaving device is again a covered stent, which are made of BMS covered with fabric or graft material.
For many years, left main coronary artery (LMCA) lesion was preferentially treated with BMS, as the danger of ST here was much higher than ISR. However, with extensive safety data with newer generation DES, BMS is no longer the preferred stent for LMCA lesion.
Saphenous venous graft lesions still are tackled with BMS by many cardiologists as in venous structure, ISR is uncommon.
Another very special indication of BMS is ST after DES implantation. However, most interventionists nowadays have shifted to DES even in this situation.
National Intervention Council (NIC) of the Cardiological Society of India collects data throughout the year from CCL all across India and presents them at the mid-term NIC conference on the following year. As per the database, in 2013, 21.3' of total stents used in India were BMS. This value came down drastically to 4.2' in 2015 (18,300 of 433,650), 5.1' in 2016 (24,611 of 478,770), and 3.25' in 2017 (16,620 of 511,389) and the latest report of 2018 which was presented in 2019 showed the number of BMS used was 10,869 of a total of 578,164 stents deployed (1.87').
As per the 2017 database, 39.39' of Indians met the cost of angioplasty of their own, whereas 43.68' got reimbursed from government and 16.93' of patients had private insurance. Thus, as in India, still, a large section of people pay out of their pockets, BMS is still useful and lifesaving for many patients.
PTCA revolutionized the treatment of obstructive CAD, and advent of stents, in turn, revolutionized the process of PTCA. Like any other stream of biotechnology, the innovations and improvements are ongoing. BMS dominated the CCL for more than 15 years. Then, three generations of DES, and finally BVS, have been introduced one after the other. The fundamental drawback of the stent remains to be the lack of optimal balance between ISR and late stent thrombosis. Whereas BMS is better for the latter, DES is far superior for the former complication. With equally fast development of the other intravascular procedures including rotational atherectomy and even laser atherectomy and a parallel explosion in pharmacotherapy, the relevance of the relative advantages and disadvantages of different types of stents is also fast changing. At present, second- and third-generation DES is the default choice in almost all scenarios across the world. However, BMS remains relevant in certain situations suh as very high chance of bleeding, inability to continue DAPT for whatever reason, very large diameter arteries, and coronary rupture. Furthermore, BMS being cheaper than DES (in India BMS costs 25' of DES), it may be the only affordable stent by many. Furthermore, as the main problem of BMS is ISR, in patients with limited life span for various reasons, and thus, ISR is relatively less relevant, BMS may still be preferred, as in all studies, rates of acute MI and all-cause mortality were not different from BMS to DES. It is reasonable to keep BMS available in the CCL for this important minority group of patients.
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Conflicts of interest
There are no conflicts of interest.
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