Acute Myocardial Infarction - The Role of Drug-eluting Stents in Treatment Strategies

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Although primary percutaneous coronary intervention (PCI) has become the cornerstone in the treatment of ST-segment elevation acute myocardial infarction (AMI), systemic fribrinolysis may still be considered for patients in areas where PCI is not accessible. The downside of initial plain balloon angioplasty, mainly coronary artery dissection and vessel re-occlusion, was effectively solved by the application of coronary stents. The incidence of target vessel failure, witnessed after bare metal stent (BMS) implantation, was dramatically reduced by the introduction of drug-eluting stents (DES), which significantly and effectively alleviate restenosis in the overall population. A minute incidence of late and very late DES thrombosis led to some safety concerns, which were soon rebutted, particularly by the development of newer generation DES. DES have consequently outplayed BMS among almost all anatomical and clinical subgroups of coronary artery disease patients. However, AMI remains one of the last contested territories. Today there is a growing body of evidence to support the use of DES as a safe and effective treatment of AMI.

Disclosure:The authors have no conflicts of interest to declare.



Correspondence Details:Ahmed A Khattab, University Hospital Bern, 3010 Bern, Switzerland. E:

Copyright Statement:

The copyright in this work belongs to Radcliffe Medical Media. Only articles clearly marked with the CC BY-NC logo are published with the Creative Commons by Attribution Licence. The CC BY-NC option was not available for Radcliffe journals before 1 January 2019. Articles marked ‘Open Access’ but not marked ‘CC BY-NC’ are made freely accessible at the time of publication but are subject to standard copyright law regarding reproduction and distribution. Permission is required for reuse of this content.

The treatment of acute myocardial infarction (AMI) has substantially improved in recent decades. Thrombolysis, the former first-line therapy, which is inexpensive and may be administered without noteworthy delay in primary care or pre-hospital settings, has been replaced by primary percutaneous coronary intervention (PCI) despite the inherent delay of transfering patients to a cardiac catheterisation laboratory. Initial wariness about stent implantation in the thrombogenic milieu of AMI has rapidly faded away and stent-based primary PCI has been shown to be the superior method of reperfusion compared with thrombolytic therapy in terms of reducing death, re-infarction and stroke.1 Restenosis can be substantially reduced by drug-eluting stents (DES), which may further improve long-term outcomes. Owing to their ability to significantly reduce the need for repeat revascularisation procedures, DES have been shown to be a more effective treatment compared with bare metal stents (BMS) despite being more expensive per se and the minimally increased risk of late and very late stent thrombosis that was observed with first generation DES, particularly when used for so-called ‘off-label’ indications. Off-label use of DES constitutes almost two-thirds of all indications in the real world. AMI remains one of these last contested territories: randomised clinical trials (RCTs) are still being conducted to prove the safety and efficacy of DES compared with BMS in this high-risk clinical setting. In this article, we shed light on the evidence and role of DES in the treatment of ST-segment elevation AMI.

Acute Myocardial Infarction – A High-risk Population

Although AMI has not been identified as a direct predictor for restenosis after BMS placement,2 patients presenting with AMI may bear lesion-related or clinical risk factors of restenosis, such as long lesions, small vessels or diabetes mellitus. Compared with BMS, the use of DES has resulted in significant reductions in angiographic in-stent late luminal loss, in-stent restenosis and repeat revascularisations among people with such lesions. At long-term follow-up, the rates of death and myocardial infarction were similar between BMS and DES in RCTs.3 Furthermore, due to the high thrombus burden and the frequently encountered coronary spasm associated with AMI, a tendency towards stent undersizing with subsequent malapposition has been reported among these patients, which again may relate to stent thrombosis4,5 and/or restenosis.6 Stent thrombosis is associated with a high incidence of myocardial infarction (50–70%) and mortality (20–40%).7,8

An apparent increase in late and very late stent thrombosis muted the initial enthusiasm about reduced target vessel revascularisation (TVR) after DES implantation. In the meantime, large RCTs have shown that the slightly higher incidence of late stent thrombosis after DES implantations compared with BMS does not translate into a higher mortality.8 Furthermore, observational studies suggest a reduction in mortality and myocardial infarction after DES compared with BMS implantation.8 The risk of DES thrombosis is increased when they are implanted in AMI rather than stable angina patients.4,9 However, this increased risk is probably outweighed by the morbidity associated with target vessel failure after BMS implantation.


The primary clinical and economic benefit of a DES is the reduction in TVR and its associated costs,10 which are estimated to be between US$1,650 and 4,678 per repeat revascularisation event avoided.11,12 However, DES require prolonged dual antiplatelet therapy (DAT), which is estimated to cost roughly US$2,500 over two years.13 Using DES not only makes the index procedure more costly but also prolonged DAT and the economic impact of late stent thrombosis have to outweigh the costs associated with repeat revascularisations. Taking these factors into account, DES may prove cost-effective in patients who are at increased risk of restenosis.11 However, in unselected coronary artery disease patients, DES have so far not been shown to be cost-effective compared with BMS. This has been shown in a four-year follow-up study comparing zotarolimus-eluting stents (Endeavor®) with BMS (Driver®)14 and in a one-year follow-up study comparing paclitaxeleluting stents (TAXUS™) with BMS (Express®).12 Given that AMI patients subjected to primary PCI may have both simple and complex lesion morphologies, and hence have a different prognosis in terms of restenosis, an individual assessment may be appropriate to make a decision about the most cost-effective treatment.

Head-to-head Comparisons of Drug-eluting Stents versus Bare Metal Stents in Acute Myocardial Infarction Patients

DES and BMS in AMI have been compared in numerous RCTs (see Table 1) and in several clinical registries. The largest RCT, which evaluated the role of DES in AMI, was the Harmonizing outcomes with revascularization and stents in acute mycocardial infarction (HORIZONS-AMI) trial, 15 which compared paclitaxel-eluting stents with BMS in 3,006 AMI patients with a 12-month follow-up. The study showed significantly reduced angiographic evidence of restenosis and TVR (5.8 versus 8.7%, hazard ratio 0.65, 95% confidence interval [CI] 0.48–0.89; p=0.006) after DES implantation. However, there were no differences in stent thrombosis and similar 12-month rates of death in both groups. At one year there were no safety concerns for DES implanted in patients with AMI. The absolute difference (95% CI) in target lesion revascularisation (TLR) favouring paclitaxel-eluting stents compared with BMS rose from 2.9% (0.8–5.0%) at 12 months to 6.0% (3.1–8.8%) at 24 months. 16 However, the performance of a routine angiographic follow-up at 13 months in this trial triggered a sharp incremental increase in the number of TLR procedures compared with the background event rate that was occurring before angiography.

The Trial to assess the use of the Cypher® stent in acute myocardial infarction treated with balloon angioplasty (TYPHOON) study17 evaluated the safety and efficacy of sirolimus-eluting stents (SES) versus BMS in 712 patients with ST-segment elevation AMI with a follow-up of one year. The primary end-point – target-vessel failure (TVF) one year after the procedure – defined as target-vessel-related death, recurrent myocardial infarction or TVR, was significantly lower in the SES group than in the BMS group (7.3 versus 14.3%, p=0.004). However, this reduction was mainly driven by a decrease in the rate of TVR (5.6 and 13.4%; p<0.001) and there was no significant difference between the two groups in the rate of death, reinfarction or stent thrombosis at one year. After a follow-up of four years18 in 501 patients in the TYPHOON study, SES demonstrated sustained efficacy to reduce TLR with no difference in death, repeat myocardial infarction or stent thrombosis between SES and BMS.

In the Paclitaxel-eluting stent versus conventional stent in myocardial infarction with ST-segment elevation (PASSION) trial,19 619 patients with AMI were randomly assigned to a paclitaxel-eluting stent or a BMS. After one year there was no significant difference between the two groups in terms of the rate of death from cardiac causes, the rate of AMI, the rate of TVR and the incidence of stent thrombosis.

After two years20 there was still no significant difference in clinical outcome and only a trend towards a lower rate of TLR in DES. At five years21 the results did not change, showing no difference in the composite end-point of cardiac death, recurrent myocardial infarction or TLR between patients treated with a DES or BMS.

In the Paclitaxel or sirolimus-eluting stent versus bare metal stent in primary angioplasty (PASEO) trial,22 270 patients with AMI were randomly assigned to a paclitaxel-eluting stent, SES or BMS. At the two-year follow-up no difference was observed in terms of death, reinfarction and combined death and/or reinfarction.

The Drug elution and distal protection in acute myocardial infarction (DEDICATION) trial23 randomised 626 patients with ST-segment elevation AMI to receive a DES or BMS. At three years, TLR was 6.1% in the DES group compared with 16.3% in the BMS group (p<0.001), and the rate of major adverse cardiac events was 11.5 versus 18.2%, respectively (p=0.02). However, all-cause mortality did not differ significantly and the occurrence of reinfarction, stroke and stent thrombosis was similar.

Another long-term follow-up trial was the MISSION! study (a prospective RCT to evaluate the efficacy of DES versus BMS for the treatment of AMI),24 which compared SES with BMS in 310 patients with ST-segment elevation AMI. After the first year of follow-up, a significant difference between SES and BMS patients for all revascularisation end-points was found. However, at the three-year follow-up, although there was still a trend towards better clinical outcomes in SES-treated patients, there were no significant differences for death, target vessel-related MI, TVR, TLR, target vessel failure (TVF) and stent thrombosis.

There is a relatively high consistency in the data obtained from RCTs comparing DES with BMS in patients with AMI showing that DES reduce revascularisation end-points; none of these trials showed a benefit of DES in reducing death, MI or stroke. The cumulative risk of stent thrombosis is also similar between DES and BMS: stent thrombosis occurs earlier in patients treated with BMS, whereas in patients treated with DES it occurs later during the follow-up.

Data from large-scale clinical registries support these findings. In a large registry from Massachusetts published in 2008,25 repeat revascularisation rates were significantly reduced with the use of DES compared with BMS in 7,217 patients with AMI during a two-year follow-up. Furthermore, two-year risk-adjusted mortality rates were lower for DES than for BMS (10.7 versus 12.8%; p=0.02).

By contrast, an analysis of the Global Registry of Acute Coronary Events (GRACE)26 suggested that among patients surviving an ST-segment elevation AMI, the mortality rate at two years in patients treated with a DES was more than double that of those treated with a BMS. However, when data from the GRACE registry for all acute coronary syndrome patients at two years were analysed together, there was no significant difference in mortality between BMS and DES (4.6 versus 2.8%).

Ongoing Studies

Two large European RCTs are directly addressing the role of DES in AMI: they have completed recruitment and are now in the follow-up phase. One of them is the Comfortable AMI (NCT00962416) trial, which is a multicentre study conducted at 12 European sites and in Israel with the aim of comparing the biolimus-eluting (Biomatrix™) with the otherwise identical bare-metal stent (Gazelle™) in unselected patients suffering from ST-segment elevation AMI. The composite end-point encompasses cardiac death, target vessel myocardial infarction (MI) and TLR at one year. The recruitment of 1,150 patients was accomplished in January 2011 and the results of the primary outcome are expected in the summer of 2012. In addition, 100 patients were included in an imaging sub-study with the aim of assessing the stent vessel wall interactions (coverage, apposition, plaque behind the strut) using multimodal imaging at baseline and at 13 months follow-up.

The EXAMINATION study (NCT00828087: a clinical evaluation of everolimus-eluting coronary stents in the treatment of patients with ST-segment elevation myocardial infarction) is a multicentre European trial that has also finished its recruitment phase. Patients presenting with ST-elevation AMI were randomised to receive either an everolimus-eluting stent or a cobalt chromium stent (non-drug-eluting stent arm). The primary outcome is a composite end-point of all-cause death, any myocardial infarction and any revascularisation at one year.

Secondary end-points will be all cause and cardiac mortality, recurrent MI, TLR, TVR, stent thrombosis, clinical device success, clinical procedure success and major and minor bleeding.

Future Perspectives

A further treatment concept was investigated in the APPOSITION clinical trial programme, which is designed to show if the STENTYS self-expanding stent (BMS and DES) can improve the treatment of acute myocardial infarction. APPOSITION II (NCT01008085) is a prospective, randomised, multicentre, international clinical trial comparing STENTYS technology with existing balloon-expandable stents in AMI patients. The APPOSITION II study27 showed that 0.51% of struts were malapposed in the STENTYS group versus 5.33% in the balloon-expandable group at three days, assessed using optical coherence tomography, representing a 10-fold reduction. The clinical impact of reducing stent malapposition among these patients will be further investigated.


Owing to the heterogeneity of anatomic and clinical subsets encountered among AMI patients presenting for primary PCI, the decision whether to use a BMS or DES in AMI may be individualised to each patient. Assessment of the risk of restenosis, stent thrombosis and bleeding are paramount. For patients with an increased risk of restenosis, DES are the preference. DES are safe and effective even long term in the treatment of AMI and are associated with a decreased need for TVR.

Future treatment concepts, such as self-expanding stents, are under investigation and may lead to a further improvement in treating AMI patients.


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