European Heart Journal Advance Access originally published online on October 24, 2007
European Heart Journal 2007 28(22):2693-2694; doi:10.1093/eurheartj/ehm474
DES or BMS in acute myocardial infarction?
Department of Cardiology, University Medical Centre Groningen Thorax Centre, Groningen, The Netherlands
* Corresponding author. Tel: +31 50 3611413; fax: +31 50 3614391. E-mail address: p.j.j.vlaar{at}thorax.umcg.nl
This editorial refers to ‘Meta-analysis of randomized trials on drug-eluting stents vs. bare-metal stents in patients with acute myocardial infarction’ by A. Kastrati et al., on page 2706
Footnotes
The opinions expressed in this article are not necessarily those of the Editors of the European Heart Journal or of the European Society of Cardiology.
The prognosis of patients with acute myocardial infarction (AMI) has been considerably improved following the introduction of reperfusion therapies. The primary aim in the acute phase of an AMI is rapid and sustained restoration of blood flow through the infarct-related artery. When logistically feasible, primary percutaneous coronary intervention (PCI) has emerged as the preferred reperfusion modality. Compared with balloon angioplasty, implantation of a bare metal stent (BMS) results in a lower rate of reocclusion and restenosis. Nevertheless, rates of target vessel revascularization after BMS implantation in patients with AMI range from 7 to 15%.1,2
The clinical presentation of the restenotic process is most often recurrence of angina, and is usually not associated with death or myocardial infarction. BMS eliminate elastic recoil and negative remodelling. However, they may induce marked neointima proliferation, resulting in in-stent restenosis. In elective PCI, drug-eluting stents (DES) have been shown to reduce neointima proliferation and thereby the risk of in-stent restenosis. These initial positive outcomes have resulted in widespread use of DES in high-risk patients, such as patients with AMI.
Kastrati et al. have reported their findings on the use of DES for primary PCI.3 The authors have performed a careful meta-analysis of eight randomized controlled trials (RCTs), comparing DES with BMS in 2786 patients. Individual patient data were available from seven of the eight studies (2476 patients). Therefore, this meta-analysis offers important time to event data regarding revascularization and thrombotic complications. This is of particular importance as it has become clear that DES may be associated with late acute stent thrombosis, a rare event but with often catastrophic clinical consequences. The authors concluded that DES in patients with AMI are effective [hazard ratio (HR) 0.38 for the risk of reintervention, P < 0.001] and safe (HR 0.80 for the risk of angiographic stent thrombosis, P = 0.43). However, before we can advocate widespread use of DES in patients with AMI, the following issues should be clarified.
Is the external validity of DES vs. BMS trials in acute myocardial infarction compromised?
Do the patients included in the DES vs. BMS trials in AMI represent a general ‘all-comers’ infarct population? In this regard, there are important differences in trial designs, in particular between PASSION and TYPHOON,4,5 the two largest trials published to date, contributing together 50% of the patients included in the meta-analysis of Kastrati et al. The PASSION trial reported no exclusion criteria regarding lesion characteristics and investigated DES in a population resembling real-world practice. However, this trial failed to show an advantage in target lesion revascularizaion (TLR) for DES vs. BMS (6.2 vs. 7.4%, P = 0.23). In contrast, the TYPHOON trial had a long list of exclusion criteria (previous PCI in the infarct-related vessel, excessive tortuosity or calcification, ostial lesions, birfucation lesions, multiple lesions, massive thrombus in infarct-related vessel, etc.) and found lower rates of target vessel revascularization (TVR) for DES (5.6 vs. 13.4%, P < 0.001). These conflicting data strongly suggest that at the present time DES should not be recommended for use in all patients with AMI. As in elective patients, additional analysis and RCTs of specific patient groups are necessary to assess which patients with AMI benefit from DES implantation and which do not.
Late and very late stent thrombosis (>1 or >3 years after implantation)
The drug and polymer composition of DES causes endothelial dysfunction, delayed endothelial healing, enhanced agonist-induced platelet aggregation, and hypersensitivity reactions.6–8 Particularly in the context of AMI, these features have raised concerns with regard to the potential higher risk of thrombotic complications when DES are implanted in a prothrombotic environment. Furthermore, the extent of the toxic effect of DES on the healing myocardium in AMI patients is largely uninvestigated.6,8 Despite these concerns, it should be noted that none of the published RCTs reported an increased risk of angiographic documented or possible stent thrombosis associated with DES.
Noteworthy is that follow-up in most studies was limited to 1 year. A registry of 505 AMI patients from the Rotterdam group showed that the benefit of DES over BMS in terms of TVR was no longer apparent after 3 years follow-up.9 In this study, late stent thrombosis occurred in four patients (2.1.%) treated with DES in the third year of follow-up against none in the BMS group. This illustrates that, with regard to late stent thrombosis, large populations and long-term follow-up are needed to establish the true incidence of this serious complication.
The clinical outcome of DES after 3–5 years
With the exception of the PASSION trial, all RCTs found an early advantage of DES in AMI, in terms of less angiographic and clinical restenosis. As demonstrated in the previously mentioned Rotterdam registry, late thrombotic events can result in more TVR in DES patients, which can negate the benefit observed in the first years. Because of the suspected higher incidence of very late stent thrombosis associated with DES compared with BMS, there should be reservations regarding conclusions about the effect of DES on long-term clinical outcome, in particular when conclusions are based on trials with follow-up limited to 1 year.
Cost-ineffectiveness is a ‘complication’ of DES implantation which cannot be neglected. The initial costs of the procedure are clearly higher with the use of DES. However, because of the lower need for revascularization procedures, there may be cost savings over the entire course of patient care. Several studies have been published assessing the cost-effectiveness of DES compared with BMS in elective patients. DES were found not to be cost-effective compared with conventional BMS, with the exception of patients at the highest risk of developing restenosis. In addition, in several RCTs, older generation, thick-strut BMS were used as the comparison to evaluate DES in AMI. As demonstrated by Kastrati et al., when two stents with different designs are compared, the stent with the thinner struts is associated with less angiographic and clinical restenosis.10 The new generation of BMS may therefore be associated with lower restenosis rates, thereby further improving cost-effectiveness of BMS compared with DES in AMI.
Long-term follow-up, in terms of death/reinfarction, of the previously described trials together with several important RCTs which are underway, such as HORIZONS AMI [3400 AMI patients randomized to paclitaxel-emitting stents (PES) or BMS] and CEZAR [352 AMI patients randomized to PES or sirolimus-eluting stents (SES)], will be necessary to resolve these issues.
The meta-analysis of Kastrati et al.3 summarizes our current knowledge of RCTs in AMI. It can be concluded that prospective studies with long-term follow-up, RCTs, and large registries will be necessary before we can conclude whether or not DES are associated with improved long-term clinical outcome. Until that time, DES implantation on a routine basis in patients with AMI should not be recommended.
Conflict of interest: none declared.
Footnotes
The opinions expressed in this article are not necessarily those of the Editors of the European Heart Journal or of the European Society of Cardiology.
doi:10.1093/eurheartj/ehm402 
References
- Stone GW, Grines CL, Cox DA, Garcia E, Tcheng JE, Griffin JJ, Guagliumi G, Stuckey T, Turco M, Carroll JD, Rutherford BD, Lansky AJ. Comparison of angioplasty with stenting, with or without abciximab, in acute myocardial infarction. N Engl J Med (2002) 346:957–966.
[Abstract/Free Full Text] - Svilaas T, van de Horst I, Zijlstra F. A Quantitative estimate of bare-metal stenting compared with balloon angioplasty in patients with acute myocardial infarction: angiographic measures in relation to clinical outcome. Heart (2007) 93:792–800.
[Abstract/Free Full Text] - Kastrati A, Dibra A, Spaulding C, Laarman GJ, Menichelli M, Valgimigli M, Di Lorenzo E, Kaiser C, Tierala I, Mehilli J, Seyfarth M, Varenne O, Dirksen MT, Percoco G, Varricchio A, Pittl U, Syvänne M, Suttorp MJ, Violini R, Schömig A. Meta-analysis of randomized trials on drug-eluting stents vs. bare-metal stents in patients with acute myocardial infarction. Eur Heart J (2007) 28:2706–2713. doi:10.1093/eurheartj/ehm402.
[Abstract/Free Full Text] - Spaulding C, Henry P, Teiger E, Beatt K, Bramucci E, Carrie D, Slama MS, Merkely B, Erglis A, Margheri M, Varenne O, Cebrian A, Stoll HP, Snead DB, Bode C. Sirolimus-eluting versus uncoated stents in acute myocardial infarction. N Engl J Med (2006) 355:1093–1104.
[Abstract/Free Full Text] - Laarman GJ, Suttorp MJ, Dirksen MT, van HL, Kiemeneij F, Slagboom T, van der Wieken LR, Tijssen JG, Rensing BJ, Patterson M. Paclitaxel-eluting versus uncoated stents in primary percutaneous coronary intervention. N Engl J Med (2006) 355:1105–1113.
[Abstract/Free Full Text] - Meier P, Zbinden R, Togni M, Wenaweser P, Windecker S, Meier B, Seiler C. Coronary collateral function long after drug-eluting stent implantation. J Am Coll Cardiol (2007) 49:15–20.
[Abstract/Free Full Text] - Nebeker JR, Virmani R, Bennett CL, Hoffman JM, Samore MH, Alvarez J, Davidson CJ, McKoy JM, Raisch DW, Whisenant BK, Yarnold PR, Belknap SM, West DP, Gage JE, Morse RE, Gligoric G, Davidson L, Feldman MD. Hypersensitivity cases associated with drug-eluting coronary stents: a review of available cases from the Research on Adverse Drug Events and Reports (RADAR) project. J Am Coll Cardiol (2006) 47:175–181.
[Abstract/Free Full Text] - Togni M, Windecker S, Cocchia R, Wenaweser P, Cook S, Billinger M, Meier B, Hess OM. Sirolimus-eluting stents associated with paradoxic coronary vasoconstriction. J Am Coll Cardiol (2005) 46:231–236.
[Abstract/Free Full Text] - Daemen J, Tanimoto S, García-García HM, Kukreja N, van de Sande M, Sianos G, de Jaegere PP, van Domburg RT, Serruys PW. Comparison of three-year clinical outcome of sirolimus- and paclitaxel-eluting stents versus bare metal stents in patients with ST-segment elevation myocardial infarction (from the RESEARCH and T-SEARCH Registries). Am J Cardiol (2007) 99:1027–1032.[CrossRef][Web of Science][Medline]
- Pache J, Kastrati A, Mehilli J, Schühlen H, Dotzer F, Hausleiter J, Fleckenstein M, Neumann FJ, Sattelberger U, Schmitt C, Müller M, Dirschinger J, Schömig A. Intracoronary stenting and angiographic results: strut thickness effect on restenosis outcome (ISAR-STEREO-2) trial. J Am Coll Cardiol (2003) 41:1283–1288.
[Abstract/Free Full Text]
CiteULike 
Connotea 
Del.icio.us What's this?
Related articles in EHJ:
- Meta-analysis of randomized trials on drug-eluting stents vs. bare-metal stents in patients with acute myocardial infarction
- Adnan Kastrati, Alban Dibra, Christian Spaulding, Gerrit J. Laarman, Maurizio Menichelli, Marco Valgimigli, Emilio Di Lorenzo, Christoph Kaiser, Ilkka Tierala, Julinda Mehilli, Melchior Seyfarth, Olivier Varenne, Maurits T. Dirksen, Gianfranco Percoco, Attilio Varricchio, Undine Pittl, Mikko Syvänne, Maarten J. Suttorp, Roberto Violini, and Albert Schömig
EHJ 2007 28: 2706-2713.[Abstract] [FREE Full Text]
This article has been cited by other articles:
|
|
 |
|
  J. Carlsson, S. K. James, J. Lindback, F. Schersten, T. Nilsson, U. Stenestrand, B. Lagerqvist, and for the SCAAR (Swedish Coronary Angiography and An Outcome of Drug-Eluting Versus Bare-Metal Stenting Used According to On- and Off-Label Criteria J. Am. Coll. Cardiol., April 21, 2009; 53(16): 1389 - 1398. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||