There Are No Current Indications to Use a Bare-Metal Stent: PRO

There remains considerable discussion as to the appropriate roles of bare-metal stents (BMS) and drug-eluting stents (DES) in optimal percutaneous revascularization. Competing themes include the lower restenosis rates particularly in later-generation DES with less concern for stent thrombosis and potentially shorter use of DAPT in patients at higher risk for bleeding. But, in contrast, BMS have also continued to improve with thinner struts and potential advantages for very short duration DAPT in special-risk patients, such as those on antithrombin therapy with atrial fibrillation. Last month in this collection's poll, the respondents reflected this diversity of opinion, as did the results of the NORSTENT trial that randomized over 9,000 patients to "modern" DES and BMS that was presented at the 2016 ESC Congress in Rome. After 5-year follow-up, there was no difference in the risk of death combined with non-fatal, spontaneous myocardial infarction, although there was a lower rate of recurrent revascularization in the DES group (see Bønaa KH, Mannsverk J, Wiseth R, et al. Drug-eluting or bare-metal stents for coronary artery disease. N Engl J Med 2016;375:1242-52).

To better understand the issues and opinions involved in the continued discussion of the relative benefits of each stent class, we invited Dr. Michael P. Thomas and Dr. Antonio Colombo to create a set of "Pro-Con" articles representing the extreme positions. Their opinions offer an excellent opportunity to provide science for the passion.

George W. Vetrovec, MD, MACC
Editorial Lead of the Invasive CV Angiography and Interventions Clinical Topic Collection


Note: This is the Pro article of a two-part "Pro-Con" set. Go to the Con article.

The development of bare-metal stents (BMS) was the second revolution in the percutaneous coronary interventional cardiology field. Stents addressed acute vessel closure and lowered the risk of target lesion revascularization (TLR). However, BMS were particularly prone to in-stent restenosis, predominantly due to neointimal hyperplasia. Following the failure of a number of treatment options to lower restenosis,1,2 drug-eluting stents (DES) provided the answer. The first-generation DES dramatically reduced TLR rates, but they were associated with the increased risk of late and very late stent thrombosis.3,4 Second-generation stents have safely overcome the limitations of BMS and first-generation DES with extremely low rates of target lesion failure and a reduction in stent thrombosis rates seen with first generation DES. These goals are now achieved without the need to prolong dual antiplatelet therapy (DAPT) when dealing with a stable patient. Therefore, current-generation DES should be the gold standard for percutaneous coronary intervention (PCI) and BMS removed from clinical practice.

Superiority of Current-Generation DES

The superiority of current-generation DES was shown in a patient-level meta-analysis of 5 randomized controlled trials involving 4,896 patients reporting that the cobalt-chromium everolimus-eluting stent (CoCr-EES; Abbott Vascular, Santa Clara, CA) was associated with a significant reduction in cardiac death (2.7 vs. 4.1%; p = 0.02), myocardial infarction (MI) (4.0 vs. 5.6%; p = 0.01), definite or probable stent thrombosis (1.3 vs. 2.6%; p = 0.001), and target vessel revascularization (TVR) (4.3 vs. 10.2%; p < 0.001) at a median follow-up of 720 days compared with BMS. Of note, approximately half (43.5%; n = 2,129) of patients underwent PCI in the setting of ST-segment elevation MI, and 2,150 (43.9%) patients underwent PCI in the setting of non-ST-segment elevation MI.5

Furthermore, a recently published network meta-analysis confirmed the long-term safety (median follow-up of 3.8 years) of current generation DES by comparing 51 trials involving DES and BMS (n = 52,158). In this study, the risk of TVR was significantly lower for all second-generation DES analyzed, and the risk of definite or probable stent thrombosis was also lower with two second-generation DES (biolimus-eluting stent [BioMatrix, Biosensors International, Singapore; Nobori, Terumo Clinical Supply, Kakamigahara, Japan] and CoCr-EES). In addition, rates of cardiac death and MI were significant reduced with CoCr-EES and phosphorylcholine-based zotarolimus-eluting stents (Medtronic, Santa Rosa, CA).6

However, although second-generation DES are superior to BMS in patients with a variety of clinical presentations including ST-segment elevation MI, they have not yet fully replaced BMS.7 Important factors that may favor BMS include 1) shorted duration of DAPT, 2) applicability to patients with high bleeding risk, 3) need for major planned noncardiac surgery, and 4) increased device cost.8

DAPT Duration

Data regarding the need for 1-month DAPT following BMS implantation in stable patients are definite, but we are still debating DAPT duration following DES. Indeed, patient characteristics, not stent design, dictate the optimal duration of DAPT. At least 6 months of DAPT is recommended post DES implant, with 1 year recommended for patients with acute coronary syndromes (ACS) independent of revascularization strategy.9,10 There are now randomized data regarding zotarolimus-eluting stents indicating that 3 months of DAPT is non-inferior to 12 months of DAPT predominantly in patients with stable coronary disease (stable angina/silent ischemia) or low-risk ACS patients (unstable angina/recent MI).11,12 Patients at high bleeding risk may require less than 3 months, but new generation DES have been proven to be superior than BMS in this setting.

High Bleeding Risk

Recently, the LEADERS FREE (Prospective Randomized Comparison of the BioFreedom Biolimus A9 Drug-Coated Stent Versus the Gazelle Bare-Metal Stent in Patients at High Bleeding Risk) trial confirmed that the use of the polymer-free BioFreedom stent (Biosensors International, Singapore) was superior to the use of BMS in patients at high bleeding risk (for example, advanced age, chronic kidney disease, concomitant anticoagulant therapy, recent history of serious bleeding, anemia, or malignancy). A total of 2,466 patients were randomized, and all patients were administered DAPT for only 1 month. The primary safety endpoint of a composite of cardiac death, MI, and stent thrombosis occurred significantly less in the drug-coated stent arm after 12-month follow-up (9.4 vs. 12.9%; p < 0.001 for non-inferiority, p = 0.005 for superiority). In addition, the primary efficacy endpoint of clinically driven TLR occurred less frequently in the DES arm (5.1 vs. 9.8%; p < 0.001).13 A sub-study of the same trial involving 659 patients presenting with ACS14 also reported that the polymer-free DES was both safer in terms of cardiac mortality (3.4 vs. 6.9%; p = 0.0490) and MI (6.9 vs. 13.8%; p = 0.005) and more efficacious than BMS in terms of clinically driven TLR (3.9 vs 9.0%; p = 0.009).

Similarly, in the ZEUS (Zotarolimus-Eluting Endeavor Sprint Stent in Uncertain DES Candidates) trial,15 1,606 patients with stable or unstable symptoms at high bleeding risk, high thrombosis risk (for example, cancer or allergy to aspirin or P2Y12 inhibitors), or low restenosis risk (for example, no planned stent <3.0mm) were randomly assigned to a zotarolimus-eluting stent (Endeavor Drug-Eluting Stent System, Medtronic Vascular, Minneapolis, MN) or BMS. The primary endpoint composed major adverse cardiac events (MACE) defined as all-cause death, MI, or TVR. The median DAPT duration was 32 days for all groups. The zotarolimus-eluting stents were superior to BMS at 12-month follow-up for primary endpoint (17.5 vs. 22.1%; p = 0.011) and definite/probable stent thrombosis (2.0 vs. 4.1%; p = 0.019). A prespecified analysis from the ZEUS trial involving 828 patients at high bleeding risk (including advanced age, oral anticoagulant therapy, prior bleeding history, and anemia)16 reported that the MACE rate was lower in the DES arm than the BMS arm (22.6 vs. 29%; p = 0.033), predominantly driven by MI (3.5 vs 10.4%; p < 0.001) and TVR (5.9 vs. 11.4%; p = 0.005). In addition, combined definite/probable stent thrombosis rates were significantly lower (2.6 vs. 6.2%; p = 0.016).

Major Planned Noncardiac Surgery

There are certain situations in which patients undergo revascularization prior to major noncardiac surgery that is planned to occur within the recommended DAPT regime time frame; therefore, some clinicians have favored BMS in this setting. Interestingly, data from a large American cohort indicated that higher MACE rates were observed with BMS if patients underwent noncardiac surgery in a time period that was generally thought to be relatively safe with BMS (45-180 days).17 In addition, observational data have suggested that there is no major difference between BMS and DES in the occurrence of MACE following DAPT cessation.18 Therefore, with the absence of high-quality data to indicate that BMS are better than newer generation DES for patients who require noncardiac surgery between 6 weeks and 6 months of PCI and randomized data showing that second-generation DES are better than BMS with short courses of DAPT, newer generation DES should be the default option in patients undergoing noncardiac surgery.

Cost

It must be stated that, initially, DES cost more than BMS to implant, but the inferior results provided by BMS lead to more revascularizations and, therefore, a greater resource burden for healthcare systems.19 Therefore, in the modern era, cost is a neutral factor in the decision algorithm for implanting either a DES or BMS.

In summary, BMS should be phased out and replaced with the superior newer-generation DES, including no-polymer DES, because there is no justification in the modern era to use a device that provides inferior results in terms of hard endpoints and is associated with a greater resource burden to healthcare systems without a demonstrated lower risk profile.

References

  1. Waksman R, White RL, Chan RC, et al. Intracoronary gamma-radiation therapy after angioplasty inhibits recurrence in patients with in-stent restenosis. Circulation 2000;101:2165-71.
  2. Holmes DR Jr, Savage M, LaBlanche JM, et al. Results of Prevention of REStenosis with Tranilast and its Outcomes (PRESTO) trial. Circulation 2002;106:1243-50.
  3. Camenzind E, Steg PG, Wijns W. Stent thrombosis late after implantation of first-generation drug-eluting stents: a cause for concern. Circulation 2007;115:1440-55.
  4. Tada T, Byrne RA, Simunovic I, et al. Risk of stent thrombosis among bare-metal stents, first-generation drug-eluting stents, and second-generation drug-eluting stents: results from a registry of 18,334 patients. JACC Cardiovasc Interv 2013;6:1267-74.
  5. Valgimigli M, Sabaté M, Kaiser C, et al. Effects of cobalt-chromium everolimus eluting stents or bare metal stent on fatal and non-fatal cardiovascular events: patient level meta-analysis. BMJ 2014;349:g6427.
  6. Palmerini T, Benedetto U, Biondi-Zoccai G, et al. Long-Term Safety of Drug-Eluting and Bare-Metal Stents: Evidence From a Comprehensive Network Meta-Analysis. J Am Coll Cardiol 2015;65:2496-507.
  7. Morice MC, Urban P, Greene S, Schuler G, Chevalier B. Why are we still using coronary bare-metal stents? J Am Coll Cardiol 2013;61:1122-3.
  8. Kassimis G, Banning AP. Is it time to take bare metal stents off the catheter laboratory shelf? Eur Heart J 2016 Jun 9 [Epub ahead of print].
  9. Kolh P, Windecker S. ESC/EACTS myocardial revascularization guidelines 2014. Eur Heart J 2014;35:3235-6.
  10. Levine GN, Bates ER, Bittl JA, et al. 2016 ACC/AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapy in Patients With Coronary Artery Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines: An Update of the 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention, 2011 ACCF/AHA Guideline for Coronary Artery Bypass Graft Surgery, 2012 ACC/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease, 2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction, 2014 AHA/ACC Guideline for the Management of Patients With Non-ST-Elevation Acute Coronary Syndromes, and 2014 ACC/AHA Guideline on Perioperative Cardiovascular Evaluation and Management of Patients Undergoing Noncardiac Surgery. Circulation 2016;134:e123-55.
  11. Feres F, Costa RA, Abizaid A, et al. Three vs twelve months of dual antiplatelet therapy after zotarolimus-eluting stents: the OPTIMIZE randomized trial. JAMA 2013;310:2510-22.
  12. Kim BK, Hong MK, Shin DH, et al. A new strategy for discontinuation of dual antiplatelet therapy: the RESET Trial (REal Safety and Efficacy of 3-month dual antiplatelet Therapy following Endeavor zotarolimus-eluting stent implantation). J Am Coll Cardiol 2012;60:1340-8.
  13. Urban P, Meredith IT, Abizaid A, et al. Polymer-free Drug-Coated Coronary Stents in Patients at High Bleeding Risk. N Engl J Med 2015;373:2038-47.
  14. Naber CK, Urban P, Ong PJ, et al. Biolimus-A9 polymer-free coated stent in high bleeding risk patients with acute coronary syndrome: a Leaders Free ACS sub-study. Eur Heart J 2016 May 17 [Epub ahead of print].
  15. Valgimigli M, Patialiakas A, Thury A, et al. Zotarolimus-eluting versus bare-metal stents in uncertain drug-eluting stent candidates. J Am Coll Cardiol 2015;65:805-15.
  16. Ariotti S, Adamo M, Costa F, et al. Is Bare-Metal Stent Implantation Still Justifiable in High Bleeding Risk Patients Undergoing Percutaneous Coronary Intervention?: A Pre-Specified Analysis From the ZEUS Trial. JACC Cardiovasc Interv 2016;9:426-36.
  17. Hawn MT, Graham LA, Richman JS, Itani KM, Henderson WG, Maddox TM. Risk of major adverse cardiac events following noncardiac surgery in patients with coronary stents. JAMA 2013;310:1462-72.
  18. Mehran R, Baber U, Steg PG, et al. Cessation of dual antiplatelet treatment and cardiac events after percutaneous coronary intervention (PARIS): 2 year results from a prospective observational study. Lancet 2013;382:1714-22.
  19. Schafer PE, Sacrinty MT, Cohen DJ, et al. Cost-effectiveness of drug-eluting stents versus bare metal stents in clinical practice. Circ Cardiovasc Qual Outcomes 2011;4:408-15.

Clinical Topics: Acute Coronary Syndromes, Anticoagulation Management, Arrhythmias and Clinical EP, Invasive Cardiovascular Angiography and Intervention, Stable Ischemic Heart Disease, Anticoagulation Management and ACS, Anticoagulation Management and Atrial Fibrillation, Atrial Fibrillation/Supraventricular Arrhythmias, Interventions and ACS, Interventions and Imaging, Interventions and Vascular Medicine, Angiography, Nuclear Imaging, Chronic Angina

Keywords: Acute Coronary Syndrome, Anemia, Angina, Stable, Angiography, Angioplasty, Balloon, Coronary, Anticoagulants, Atrial Fibrillation, Diabetes Mellitus, Drug-Eluting Stents, Myocardial Infarction, Neoplasms, Percutaneous Coronary Intervention, Pulmonary Embolism, Risk Factors, Stroke, Thrombosis, Ticlopidine, Warfarin, Hyperplasia, Hypersensitivity


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