Stent thrombosis with drug-eluting and bare-metal stents: evidence from a comprehensive network meta-analysis

doi:10.1016/S0140-6736(12)60324-9

The Lancet

Volume 379, Issue 9824, 14–20 April 2012, Pages 1393-1402

https://doi.org/10.1016/S0140-6736(12)60324-9 Get rights and content

Summary

Background

The relative safety of drug-eluting stents and bare-metal stents, especially with respect to stent thrombosis, continues to be debated. In view of the overall low frequency of stent thrombosis, large sample sizes are needed to accurately estimate treatment differences between stents. We compared the risk of thrombosis between bare-metal and drug-eluting stents.

Methods

For this network meta-analysis, randomised controlled trials comparing different drug-eluting stents or drug-eluting with bare-metal stents currently approved in the USA were identified through Medline, Embase, Cochrane databases, and proceedings of international meetings. Information about study design, inclusion and exclusion criteria, sample characteristics, and clinical outcomes was extracted.

Findings

49 trials including 50 844 patients randomly assigned to treatment groups were analysed. 1-year definite stent thrombosis was significantly lower with cobalt-chromium everolimus eluting stents (CoCr-EES) than with bare-metal stents (odds ratio [OR] 0·23, 95% CI 0·13–0·41). The significant difference in stent thrombosis between CoCr-EES and bare-metal stents was evident as early as 30 days (OR 0·21, 95% CI 0·11–0·42) and was also significant between 31 days and 1 year (OR 0·27, 95% CI 0·08–0·74). CoCr-EES were also associated with significantly lower rates of 1-year definite stent thrombosis compared with paclitaxel-eluting stents (OR 0·28, 95% CI 0·16–0·48), permanent polymer-based sirolimus-eluting stents (OR 0·41, 95% CI 0·24–0·70), phosphorylcholine-based zotarolimus-eluting stents (OR 0·21, 95% CI 0·10–0·44), and Resolute zotarolimus-eluting stents (OR 0·14, 95% CI 0·03–0·47). At 2-year follow-up, CoCr-EES were still associated with significantly lower rates of definite stent thrombosis than were bare-metal (OR 0·35, 95% CI 0·17–0·69) and paclitaxel-eluting stents (OR 0·34, 95% CI 0·19–0·62). No other drug-eluting stent had lower definite thrombosis rates compared with bare-metal stents at 2-year follow-up.

Interpretation

In randomised studies completed to date, CoCr-EES has the lowest rate of stent thrombosis within 2 years of implantation. The finding that CoCr-EES also reduced stent thrombosis compared with bare-metal stents, if confirmed in future randomised trials, represents a paradigm shift.

Funding

The Cardiovascular Research Foundation.

Introduction

Randomised controlled trials,1, 2 meta-analysis,³ and observational studies⁴ have consistently shown reduced rates of angiographic restenosis and ischaemia-driven target vessel revascularisation with drug-eluting stents compared with bare-metal stents. As a result, most percutaneous coronary interventions in Europe and the USA are done with drug-eluting rather than bare-metal stents. However, the high rates of early and late stent thrombosis after discontinuation of dual antiplatelet agents with drug-eluting stents, and the ongoing propensity for thrombosis after the first year with first-generation Cypher sirolimus-eluting stents (SES; Cordis Corp, Miami Lakes, FL, USA) and Taxus paclitaxel-eluting stents (PES; Boston Scientific, Natick, MA, USA), have raised safety concerns.5, 6 To address these issues, new drug-eluting stents have been developed with novel materials, designs, and delivery systems, with improved biocompatible polymers, and new antiproliferative agents compared with their predecessors. However, most of these second generation stents were approved in non-inferiority trials compared with first generation drug-eluting stents.7, 8, 9, 10 Therefore, few studies have directly compared second generation drug-eluting stents with each other¹¹ or with bare-metal stents. Recently, the EXAMINATION trial¹² comparing Xience V cobalt-chromium everolimus-eluting stents (CoCr-EES; Abbott Vascular, Santa Clara, CA, USA) with bare-metal stents in patients with ST-segment elevation myocardial infarction (STEMI) showed significantly reduced rates of stent thrombosis in patients treated with CoCr-EES. However, this trial was not powered to show differences in stent thrombosis and therefore whether those findings are real or attributable to chance remains unclear.

In view of the low frequency of stent thrombosis, very large sample sizes are needed to accurately estimate treatment differences between devices. Network meta-analysis and mixed treated comparisons are novel research methods capable of comparing different treatments using a common reference treatment, and their role in clinical research has been established.¹³ An earlier network meta-analysis in 2007 in which only bare-metal stents and first generation drug-eluting stents were compared strengthened concerns about late and very late stent thrombosis with PES.¹⁴ Since that publication, many additional randomised trials have been done with second generation as well as first generation drug-eluting stents. Accordingly, we undertook an updated contemporary, comprehensive network meta-analysis to investigate whether there are major differences in the risk of stent thrombosis between first and second generation drug-eluting stents, or between drug-eluting and bare-metal stents.

Section snippets

Study design

In this network meta-analysis, we compared the risk of definite and definite or probable stent thrombosis between drug-eluting stents currently approved by the US Food and Drug Administration (FDA) and between drug-eluting and bare-metal stents. We restricted our analyses to FDA-approved drug-eluting stents because these currently are the devices with the most robust demonstrations of safety and efficacy. Thus, the drug-eluting stents studied in the present report were SES, PES (both Express

Results

Figure 1 shows the flow diagram for the study analysis. Of 2602 potentially relevant articles initially screened, 49 trials met the inclusion criteria and were included in the final meta-analysis (appendix pp 1–5), with a total of 50 844 patients. Figure 2 shows the evidence network. Table 1 shows the major characteristics of the included trials. Six studies were done exclusively in patients with diabetes, 11 studies in patients with STEMI, one study in patients with saphenous vein grafts, one

Discussion

We report the largest and most comprehensive study to date comparing the rates of ARC definite and definite or probable stent thrombosis between different types of drug-eluting stent and between drug-eluting and bare-metal stents. There were three principal findings: (1) CoCr-EES were associated with significantly lower rates of 1-year and 2-year definite stent thrombosis than were bare-metal stents, a result not present with other drug-eluting stents; (2) the reduction in stent thrombosis with

References (31)

M Pfisterer et al.
Late clinical events after clopidogrel discontinuation may limit the benefit of drug-eluting stents: an observational study of drug-eluting versus bare-metal stents
J Am Coll Cardiol
(2006)
E Kedhi et al.
Second-generation everolimus-eluting and paclitaxel-eluting stents in real-life practice (COMPARE): a randomised trial
Lancet
(2010)
F Song et al.
Adjusted indirect comparison may be less biased than direct comparison for evaluating new pharmaceutical interventions
J Clin Epidemiol
(2008)
C Stettler et al.
Outcomes associated with drug-eluting and bare-metal stents: a collaborative network meta-analysis
Lancet
(2007)
E Schampaert et al.
The Canadian study of the sirolimus-eluting stent in the treatment of patients with long de novo lesions in small native coronary arteries (C-SIRIUS)
J Am Coll Cardiol
(2004)
M Joner et al.
Pathology of drug-eluting stents in humans: delayed healing and late thrombotic risk
J Am Coll Cardiol
(2006)
M Joner et al.
Endothelial cell recovery between comparator polymer-based drug-eluting stents
J Am Coll Cardiol
(2008)
G Nakazawa et al.
Pathological findings at bifurcation lesions: the impact of flow distribution on atherosclerosis and arterial healing after stent implantation
J Am Coll Cardiol
(2010)
RJ Krone et al.
Acceptance, panic, and partial recovery the pattern of usage of drug-eluting stents after introduction in the U.S. (a report from the American College of Cardiology/National Cardiovascular Data Registry)
JACC Cardiovasc Interv
(2010)
L Raber et al.
Long-term comparison of everolimus-eluting and sirolimus-eluting stents for coronary revascularization
J Am Coll Cardiol
(2011)

SL Chin-Quee et al.

Endothelial cell recovery, acute thrombogenicity, and monocyte adhesion and activation on fluorinated copolymer and phosphorylcholine polymer stent coatings

Biomaterials

(2010)

MC Morice et al.

A randomized comparison of a sirolimus-eluting stent with a standard stent for coronary revascularization

N Engl J Med

(2002)

GW Stone et al.

A polymer-based, paclitaxel-eluting stent in patients with coronary artery disease

N Engl J Med

(2004)

L Mauri et al.

Stent thrombosis in randomized clinical trials of drug-eluting stents

N Engl J Med

(2007)

JV Tu et al.

Effectiveness and safety of drug-eluting stents in Ontario

N Engl J Med

(2007)

Cited by (839)

Aneurysm Treatment With the Pipeline Vantage Embolization Device in Retrospective Evaluation: Periprocedural Results from the Pipe-VADER Study
2024, World Neurosurgery
The Pipeline Vantage Embolization Device is a fourth-generation flow diverter with an antithrombotic coating and a reduced profile compared to previous Pipeline versions. The objective of this study was to evaluate the procedural feasibility, safety, and efficacy of this device.
The Pipe-VADER study was designed as a retrospective, observational study of consecutive patients treated with the Vantage at 3 neurovascular centers. Patient and aneurysm characteristics, procedural parameters, early complications, and extent of postinterventional contrast retention were analyzed on an intention-to-treat basis.
Twenty-eight patients with 31 aneurysms (median size: 5.0 mm, posterior circulation: 4 [12.9%], ruptured: 5 [16.1%]) were included. The technical success rate was 100%, with multiple stents used in 4/30 (13.3%) procedures. Of the 30 procedures, adjunctive coiling was performed in 3 (10.0%) and balloon angioplasty in 2 (6.7%). Median procedure time was 62 minutes. Procedural ischemic stroke occured in 4 (13.3%) cases, whereof 2 were major strokes (6.6%). There were no hemorrhagic complications. Initial contrast retention was observed in 29/31 (93.5%) aneurysms. All 27 overstented side vessels were patent at the end of the procedure. Short-term follow-up (median: 5 months) showed complete and favorable occlusion rates of 70% (14/20) and 80% (16/20), respectively.
The new Pipeline Vantage appears to be safe and feasible for the treatment of intracranial aneurysms and warrants further evaluation.
The utility and effectiveness of the newer generation high-resolution coronary computed tomography angiography in the evaluation of coronary in-stent restenosis
2024, Current Problems in Cardiology
The importance of coronary computerized tomography angiography (CCTA) in detecting native coronary artery stenosis has been established. However, very few studies investigated the efficacy of CCTA in the assessment of in-stent restenosis (ISR) in symptomatic patients after percutaneous coronary intervention (PCI).
To evaluate the value of CCTA in diagnosing ISR.
We included 102 symptomatic patients with stable angina, presented one to five years after PCI. All patients were subjected to CCTA, and the patients with significant coronary artery disease were directed for invasive coronary angiography (ICA). CCTA results were compared to ICA as the gold standard tool for detecting ISR.
In 88 (86.3 %) patients, CCTA could successfully exclude ISR together with the ICA (true negative), but in two cases, ICA detected an ISR which was not detected by CCTA (false negative). In eight patients, CCTA detected ISR. These were confirmed by ICA (true positive) and revascularized. In four patients (3.9 %), ISR was suspected by CCTA but excluded by ICA (false positive). In our study, according to the agreement of CCTA in detection or exclusion of ISR, sensitivity, specificity, PPV, NPV and accuracy were 80.0 %, 96.65 %, 66.67 %, 97.78 %, 94.12 %, respectively. These results were statistically significant (P < 0.001).
In up to 86 % of symptomatic patients with previous PCI, ISR was accurately excluded by CCTA. CCTA was demonstrated by this study as a high yielding tool for ruling out ISR, abolishing the need for more invasive and expensive diagnostic procedures.
Prognostic Impact of Drug-Coated Balloons in Patients With Diabetes Mellitus: A Propensity-Matched Study
2023, American Journal of Cardiology
Patients with diabetes mellitus (DM) are at higher risk of restenosis and stent thrombosis after percutaneous coronary intervention (PCI) and drug-eluting stent (DES) positioning. Whether drug-coated balloons (DCB) can offer any benefit in this subset of patients has been seldom cleared out and was the aim of the present propensity-matched cohort study, that compared the prognostic impact of DCB versus DES in patients with DM who underwent PCI. Patients with DM enrolled in the NOvara-BIella-TREnto (NOBITRE) Registry were identified and matched according to propensity score, to a control population of patients with DM treated with DES. The primary study end point was the occurrence of major adverse cardiovascular events (MACEs). A total of 150 patients were identified in the DCB group and matched with 150 DES-treated patients. Patients treated with DCB displayed more often a previous cardiovascular history and received a more complete pharmacological therapy. Target vessel diameter and the percentage of stenosis were lower in patients with DCB, whereas binary in-stent restenosis was more common (p <0.001, p = 0.003, and p <0.001, respectively). Paclitaxel-eluting balloon represented the most common strategy in the DCB group, whereas Zotarolimus-eluting stents were used in half of the DES population. At a median follow-up of 545.5 days, MACE occurred in 54 (19.4%) of patients, with no difference according to the PCI strategy (21.6% vs 17.3%, adjusted hazard ratio [95% confidence interval] 1.51 [0.46 to 4.93], p = 0.50). Major ischemic end points were slightly increased in patients treated with DCB, whereas overall death was significantly reduced (3.6% vs 10.9%; adjusted hazard ratio [95% confidence interval] 0.27 [0.08 to 0.91], p = 0.03).
In conclusion, the present propensity-matched study shows that, in patients with DM who underwent PCI for in-stent restenosis or de novo lesions, the use of DCB is associated with a similar rate of MACE and a modest increase in target lesion failure, but a significantly improved survival as compared with DES.
Structural and temporal dynamics analysis on drug-eluting stents: History, research hotspots and emerging trends
2023, Bioactive Materials
This review aims to explore the history, research hotspots, and emerging trends of drug-eluting stents(DES)in the last two decades from the perspective of structural and temporal dynamics.
Publications on DES were retrieved from WoSCC. The bibliometric tools including CiteSpace and HistCite were used to identify the historical features, the evolution of active topics, and emerging trends on the DES field.
In the last 20 years, the field of DES is still in the hot phase and there is a wide range of extensive scientific collaborations. In addition, active topics emerge in different periods, as evidenced by a total of 41 disciplines, 511 keywords, and 1377 papers with citation bursts. Keyword clustering anchored five emerging research subfields, namely #0 dual antiplatelet therapy, #3 drug-coated balloon, #4 bifurcation, 5# rotational atherectomy, and 6# quantitative flow ratio. The keyword alluvial map shows that the most persistent research concepts in this field are thrombosis, restenosis, etc., and the emerging keywords are paclitaxel eluting balloon, coated balloon, drug-eluting balloon, etc. There are 7 recent research subfields anchored by reference clustering, namely #2 dual antiplatelet therapy, #4 drug-coated balloon, #5 peripheral artery disease, #8 fractional flow reserve, #10 bioresorbable vascular scaffold, # 13 intravascular ultrasound, #14 biodegradable polymer.
The findings based on the bibliometric studies provide the current status and trends in DES research and may help researchers to identify hot topics and explore new research directions in this field.
Ten-year patterns of stent thrombosis after percutaneous coronary intervention with new- versus early-generation drug-eluting stents: insights from the DECADE cooperation
2022, Revista Espanola de Cardiologia
El metanálisis DECADE es un análisis de datos de pacientes individuales de ensayos de stents liberadores de fármacos (SLF) con un seguimiento de 10 años. El objetivo del estudio es analizar el riesgo de trombosis definitiva del stent (TS) hasta 10 años después de la intervención coronaria percutánea (ICP) en pacientes tratados con DES de primera y de nueva generación.
Se agruparon los datos de pacientes individuales de cinco ensayos de SLF con un seguimiento de 10 años. El objetivo primario fue la TS hasta 10 años después de la ICP. Los pacientes se dividieron en 2 grupos según la generación de stent implantada (primera y nueva). El análisis de los datos de los participantes individuales se realizó mediante el enfoque de una etapa.
Se incluyeron 9.700 pacientes, 6.866 en el grupo de SLF nuevos y 2.834 en el grupo de SLF de primera generación. A los 10 años, la TS se produjo en 69 de los 6.866 pacientes tratados con SLF de nueva generación y en 91 de los 2.834 pacientes tratados con la SLF de primera generación (1,0% frente a 3,5%, razón de tasas 0,32; IC95%, 0,23-0,45). La tasa de TS fue menor en el grupo de SLF de nueva generación en comparación con el grupo de SLF de primera, de 1-5 años (razón de tasas 0,14; IC95%, 0,08-0,26) y de 5-10 años (razón de tasas 0,23; IC95%, 0,08-0,61) después de la ICP.
La incidencia de TS hasta 10 años después de la ICP con los SLF de nueva generación es del 1%. Los SLF de nueva generación se asocian a una menor incidencia de TS a 10 años comparados con los SLF de primera generación, especialmente después de 1 año de la ICP.
The DECADE cooperation is a pooled analysis of individual patient data from drug-eluting stent (DES) trials with a 10-year follow-up. This analysis reports the risk of definite stent thrombosis (ST) through to 10 years after percutaneous coronary intervention (PCI) in patients treated with early- and new-generation DES.
Individual patient data from 5 DES trials with a 10-year follow-up were pooled. The primary endpoint was definite ST up to 10 years after PCI. Patients were divided into 2 groups as per the generation of DES implanted (early and new DES). Individual participant data were analyzed using a 1-stage approach.
We included 9700 patients, 6866 in the new DES group and 2834 in the early DES group. Through to 10 years, definite ST occurred in 69 of 6866 patients treated with new DES and in 91 of 2834 patients treated with early DES (1.0% vs 3.5%, adjusted hazard ratio, 0.32; 95%CI, 0.23-0.45). The rate of definite ST was lower in the new DES group than in the early DES group from 1 to 5 years (rate ratio, 0.14; 95%CI, 0.08-0.26) and from 5 to 10 years (rate ratio, 0.23; 95%CI, 0.08-0.61) after PCI.
The incidence of definite ST through to 10 years after PCI with new-generation DES was 1%. New-generation DES are associated with a lower 10-year incidence of definite ST than early-generation DES, particularly beyond 1 year after PCI.
The Ongoing Saga of the Evolution of Percutaneous Coronary Intervention: From Balloon Angioplasty to Recent Innovations to Future Prospects
2022, Canadian Journal of Cardiology
The advances in percutaneous coronary intervention (PCI) have been, above all, dependent on the work of pioneers in surgery, radiology, and interventional cardiology. From Grüntzig’s first balloon angioplasty, PCI has expanded through technology development, improved protocols, and dissemination of best-practice techniques. We can nowadays treat more complex lesions in higher-risk patients with favourable results. Guide wires, balloon types and profiles, debulking techniques such as atherectomy or lithotripsy, stents, and scaffolds all represent evolutions that have allowed us to tackle complex lesions such as an unprotected left main coronary artery, complex bifurcations, or chronic total occlusions. Best-practice PCI, including physiology assessment, imaging, and optimal lesion preparation are now the gold standard when performing PCI for sound indications, and new technologies such as intravascular lithotripsy for lesion preparation, or artificial intelligence, are innovations in the steps of 4 decades of pioneers to improve patient care in interventional cardiology. In the present review, major innovations in PCI since the first balloon angioplasty and also uncertainties and obstacles inherent to such medical advances are described.
Les avancées dans le domaine de l’intervention coronarienne percutanée (ICP) sont le résultat du travail de pionniers en chirurgie, en radiologie et en cardiologie interventionnelle. Depuis la première angioplastie par ballonnet du D^r Grüntzig, l’ICP a progressé grâce à la mise au point de nouvelles technologies et de protocoles améliorés, et par la diffusion des bonnes pratiques de ces différentes techniques. Il est désormais possible de traiter des lésions plus complexes chez des patients présentant des risques plus élevés et d’obtenir des résultats favorables. L’avènement des fils-guides, des nouveaux types et profils de ballonnets, des techniques de réduction du volume de plaque, comme l’athérectomie et la lithotripsie et des endoprothèses nous permet maintenant de nous attaquer à des lésions complexes, telles que la sténose du tronc commun gauche non protégé, les bifurcations complexes et les occlusions totales chroniques. L’ICP faisant appel aux meilleures pratiques, notamment l’évaluation physiologique, les examens d’imagerie et la préparation optimale des lésions, est maintenant l’approche de référence lorsqu’une ICP est indiquée, et de nouvelles technologies, comme la lithotripsie intravasculaire pour préparer les lésions ou le recours à l’intelligence artificielle, s’inscrivent dans la continuité de quatre décennies de travaux pionniers dans la recherche de meilleurs soins en cardiologie interventionnelle. Notre article de synthèse présente les innovations principales dans le domaine de l’ICP depuis la première angioplastie par ballonnet, ainsi que les incertitudes et les obstacles propres à de telles avancées médicales.

View all citing articles on Scopus

View full text

ArticlesStent thrombosis with drug-eluting and bare-metal stents: evidence from a comprehensive network meta-analysis

Summary

Background

Methods

Findings

Interpretation

Funding

Introduction

Section snippets

Study design

Results

Discussion

J Am Coll Cardiol

Lancet

J Clin Epidemiol

Lancet

J Am Coll Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

JACC Cardiovasc Interv

J Am Coll Cardiol

Biomaterials

A randomized comparison of a sirolimus-eluting stent with a standard stent for coronary revascularization

N Engl J Med

A polymer-based, paclitaxel-eluting stent in patients with coronary artery disease

N Engl J Med

Stent thrombosis in randomized clinical trials of drug-eluting stents

N Engl J Med

Effectiveness and safety of drug-eluting stents in Ontario

N Engl J Med

Articles
Stent thrombosis with drug-eluting and bare-metal stents: evidence from a comprehensive network meta-analysis