Currently, the optimal treatment of acute myocardial infarction (AMI) in patients presenting with ST-segment-elevation MI (STEMI) is to perform a primary percutaneous coronary intervention (PCI) as quickly as possible after onset of symptoms.1,2 While this has become the standard of care for treating AMI, several factors, including limited availability of catheterisation laboratories in a specific region, may result in thrombolytic therapy being administered in place of PCI. Similarly, if the time to reach a medical centre with PCI capability is greater than 45 minutes, PCI is unlikely to be the first-line therapy. Performing thromboaspiration in the affected area to remove the clot prior to the implantation of a stent during PCI should be included as a crucial step and has shown additional benefits in patient outcomes.3 The typical PCI routine should therefore be thromboaspiration followed by stent implantation.
Substantial advances have been seen in medical technology in recent years, resulting in fewer complications associated with PCI procedures. A recent prospective study of data abstracted from PCI report forms in New York State4 showed a relatively low reported rate of 3.36% for any complications one month post-implantation over the eight years examined (1999–2006). In addition, when comparing rates between early (1999–2002) and recent (2003–2006) periods, a decline in complications was observed. A significant difference was seen, whereby all complications were reduced from 4% in the early period to 2.7% in the recent period (p<0.001). Although not statistically significant, there was also a slight decline in death over the years.4 However, despite these improvements, complications still occur during and after PCI procedures.
Two major unresolved issues in the treatment of AMI include the inability to restore blood flow to the heart during primary PCI and the risk of stent thrombosis. The inability to restore blood flow to the heart is a serious problem that is both potentially fatal and highly unpredictable. After a PCI, the risk of occurrence of stent thrombosis is greatest one to two weeks after the procedure. Stent thrombosis is associated with severe medical problems in the patient. Although the rate of presumed stent thrombosis remains low, with no significant change since 1999,4 it remains a serious cause for concern among physicians and patients alike.
Stent Thrombosis and Stent Malapposition
Stent thrombosis can occur shortly after a PCI has been performed. The degree of stent thrombosis has been categorised as being acute (0–24 hours), subacute (one to 30 days) or late (one to 12 months) depending on how soon it occurs after the procedure.5 In extremely rare cases, stent thrombosis can also occur over one year or even 10 years after implantation.6 The rate of stent thrombosis occurring within one month of a PCI has been estimated to be 0.53%, with the rate of presumed stent thrombosis cases being 0.82%.4 Other estimates have placed the total incidence of stent thrombosis at 1–4%, occurring more frequently in patients with STEMI.5
A recent study attempted to determine predictors of stent thrombosis.5 Evaluating only cases of STEMI, the study showed that 3.3% of the 3,203 eligible participants experienced stent thrombosis within one year of implantation. Different factors were associated with the different categories of stent thrombosis within the study. However, the type of stent selected (drug-eluting versus bare-metal) had no impact on the incidence of stent thrombosis during the first year. Furthermore, the rate of stent thrombosis appeared to be higher in patients receiving a primary PCI for AMI in an emergency situation relative to those undergoing previously planned procedures.
A major cause of stent thrombosis is malapposition of the stent leading to thrombus formation.7 Due to the large thrombus load and vasoconstriction of the artery at the time of the PCI procedure, the vessel seen on screen can appear smaller than it actually is. As a result, interventional cardiologists may underestimate the size of the artery and consequently use an undersized stent. In this situation, over the hours and days following the PCI, and after clot resolution and vasodilation, the stent diameter will be smaller than the artery diameter. This causes malapposition, with the stent no longer making optimal contact with the vessel wall. This probably increases the risk of thrombus formation beginning between the stent and the tissue. Thrombus formation can eventually lead to stent thrombosis.
Stent malapposition can also occur much later after implantation. Estimates have placed the overall incidence of late stent malapposition at 4–5%.8 This phenomenon has been studied with both bare-metal and drug-eluting stents.9–11 Hong et al.9 examined 881 patients with bare-metal stent implantation and concluded that late stent malapposition occurs in approximately 5% of patients after implantation. One of the major predictors of late stent malapposition occurrence was primary stenting in AMI. This highlights the increased risk of adverse events in patients undergoing PCI for AMI.
Antiplatelet drugs have been used to reduce the rate of stent thrombosis. Prasugrel has been shown to be effective in preventing thrombotic complications, including stent thrombosis, after primary PCI resulting from acute coronary syndromes.12,13 Another option is the use of self-expanding stents, which form a novel class of devices that could potentially reduce the risk of stent thrombosis.
Developments in Stenting – A Novel Self-expanding Stent
Considering the potentially fatal consequences of stent malapposition and thrombosis, proper stent selection becomes critical when performing a PCI to treat AMI patients. Problems can arise when the chosen stent is ultimately too large or too small for the artery in question. If the stent proves to be too large, the artery may rupture. However, if the selected stent is too small, there is an increased risk of restenosis. Recently, a novel self-expanding stent was developed by Stentys™ that has the potential to minimise this problem. The self-expanding technology is proposed to improve apposition, reducing the risk of subsequent thrombosis. The self-expanding properties of the stent allow the device to adjust its size according to changes exerted by the artery after a PCI (see Figure 1). In addition, in the presence of a significant side branch, the stent has unique disconnecting features allowing uncompromised opening of the side-branch opening. This new design may therefore become an important addition to the range of devices available to physicians.
An early case study and the first reported use of this self-expanding stent in humans showed encouraging results in STEMI.14 A 69-year-old woman presented with an occluded proximal left anterior descending artery. She underwent primary PCI in which the vessel was successfully treated with thrombosuction of the clot and subsequently fitted with a Stentys self-expandable stent. Intravascular ultrasound examination (IVUS) after the procedure and during a five-day follow-up showed that although the vessel diameter had increased, there was good apposition of the stent. The patient was eventually released with no serious adverse events. The positive findings in this case warrant clinical trials to substantiate the safety and tolerability of this novel device.14
The APPOSITION I Study
Based on preliminary observations, the APPOSITION I study was conducted to examine the use of the novel self-expanding stent in AMI.15 This prospective, non-randomised, single-arm, multicentre study was designed to address several key questions. The first main goal was to determine the technical feasibility of implanting self-expanding stents in patients for the treatment of AMI.
The investigators were also interested in determining the amount of change, in terms of size, an artery undergoes by comparing the vessel during and after stent implantation, and whether the self-expandable stent would be able to follow any potential growth three days and six months after implantation.
A total of 25 patients were enrolled in this study between March 2009 and October 2009 at five European clinical sites. Patients were eligible for enrolment if they presented with an AMI that was to be treated by primary PCI and had an occlusion of a coronary artery that was suitable for implantation of a self-expanding stent. Subjects underwent a PCI in which the thrombus was removed and a self-expanding stent implanted. An IVUS was performed immediately following the procedure and patients were to return to the laboratory for follow-up three days and six months afterwards for reassessment of artery and stent sizes. Study end-points included stent apposition at three days and the incidence of any major adverse cardiac events (MACE) at discharge and during follow-up.
Preliminary results from 20 of the patients were recently presented at the Transcatheter Cardiovascular Therapeutics Conference in San Francisco. Data collected using IVUS (n=12) three days after stent implantation showed a 20% increase in the minimum lumen area compared with baseline (p=0.002). This confirms the experiences of clinicians, who often notice an enlargement in artery diameter several days after a PCI procedure. Furthermore, the self-expanding stent was able to follow this artery enlargement with excellent apposition. There was a trend towards an improvement in apposition over the three-day period (paired n=3) as determined by optical coherence tomography (OCT). No MACE was reported for the first 20 patients at 30-day follow-up. These early findings are encouraging and suggest that this new self-expanding stent is suitable for the treatment of AMI.
Clinical Implications and Future Developments
Based on these early results, it appears that in the AMI setting, patients can be treated effectively and safely by PCI with a self-expanding stent. As longer-term follow-up data become available, the potential of the self-expanding properties of the novel device in terms of minimising malapposition and reducing the risk of stent thrombosis will become clearer, especially in the setting of treatment of acute coronary syndromes.
Currently, the APPOSITION II study is in progress. This study will compare the self-expanding stent with a balloon-expanding stent in the AMI setting. A total of 80 STEMI patients across 10 European sites will be randomised to receive either a Stentys stent or a balloon-expanding stent after a PCI. OCT will be performed immediately after implantation and after three days to visualise the stent. The primary end-point is the percentage of struts not apposed to the vessel wall in each group. If this and future studies continue to demonstrate promising results for a self-expanding stent over balloon-expanding models, it may prompt the development of a drug-eluting, self-expanding stent.
Summary and Conclusion
The prevalence of AMI is likely to rise in the coming years with the overall population getting older and co-morbidities such as obesity becoming more common. Primary PCI is the current standard of care for the majority of STEMI patients. Several forms of stent are currently available. However, malapposition can increase the risk of stent thrombosis and remains a major unresolved issue. The introduction of a novel self-expandable stent has provided an extra option. Early clinical trials with this novel self-expanding stent have produced promising data in the AMI setting, and further studies will determine the potential of this novel stent in reducing the risk of stent thrombosis.