Table of Contents  

Delle Karth: Interventional strategies for patients with coronary artery disease

Introduction

Although there has been a marked decrease over the decades in short- and long-term mortality among patients hospitalized for myocardial infarction (MI),1 coronary artery disease (CAD) is still the leading cause of death worldwide.2 The introduction of emergency percutaneous coronary intervention (PCI) has been an important step towards a better outcome after MI. However, although the benefit of PCI in patients with acute coronary syndrome (ACS) is clearly established, the role of PCI in stable CAD patients is still under debate.

Percutaneous coronary intervention for patients with acute coronary syndrome

The optimal reperfusion strategy for ST-elevation myocardial infarction (STEMI) is an emergency PCI.3 This achieves normal blood flow in the infarct-related artery in approximately 85–90% of cases,46 and is superior to systemic thrombolysis when it can performed within recommended time limits.7 The main focus for a successful emergency PCI programme is to reduce the total ischaemic time – that is, the time taken from vessel closure and onset of pain in conscious patients to the successful mechanical reopening. Whereas the time from onset of pain to first medical contact (FMC) is influenced by how quickly the patient reports his or her condition (patient delay), and is therefore difficult to improve, the time from FMC to mechanical reopening (system delay) is largely determined by organizational processes. Recent guidelines emphasize important aspects of successful STEMI networks to ensure optimal patient treatment. These include clearly defined geographical areas of responsibility, shared protocols, well-trained ambulance staff in appropriately equipped ambulances or helicopters, and direct transport to the catheterization laboratory, bypassing the emergency department. PCI centres must deliver a 24/7 service and be able to start an emergency PCI as soon as possible, i.e. within 60 minutes of the initial emergency telephone call. Although the optimal size of catchment areas is not clear, European STEMI networks currently cover between 300 000 and 1 million inhabitants each. Areas where an emergency PCI cannot be performed within the timeframes listed in Figure 1 should establish a system of rapid thrombolysis and immediate transfer of patients to a PCI-capable centre.

FIGURE 1

Pre-hospital and in-hospital management and reperfusion strategies within 24 hours of FMC. Reproduced with permission of Oxford University Press (UK) © European Society of Cardiology www.escardio.org/guidelines. Steg PG, James SK, Atar D, et al. ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: the Task Force on the management of ST-segment elevation acute myocardial infarction of the European Society of Cardiology (ESC). Eur Heart J 2012; 33:2569–619.7

6-1-13-fig1.jpg

With regard to STEMI, several specific issues should be considered in relation to PCI procedure.

  • It has been shown that the transradial approach reduces bleeding complications, which also translates into a survival benefit.8,9 However, one prerequisite for a successful transradial programme in STEMI patients is adequate experience with this route, and this may limit the applicability of these findings, especially in low-volume centres.

  • The first goal in emergency PCI is to restore adequate blood flow as soon as possible in the infarct-related artery. This includes quick passage of a wire through the site of the ruptured plaque, most often using a general workhorse guidewire (endpoint of the ‘door-to-balloon’ time), and a careful strategy to avoid thrombus dislodgement with distal embolization. Every mechanical manipulation at the site of the ruptured plaque must be carefully balanced against the risk of distal embolization.

  • Thrombus aspiration via a dedicated catheter regularly forms the first-line strategy in emergency PCI management. It has been shown in a single-centre study that routine thrombus aspiration results in better myocardial reperfusion indices and a reduction in 1-year mortality.4 However, in contrast to the proven effectiveness of intracoronary abciximab administered via a perfusion balloon, a recent multicentre trial could not affirm the usefulness of thrombus aspiration.5

  • In cases of acute MI, selecting the appropriate stent size is made difficult by persistent thrombi and/or distal coronary vasospasm. Ideally, vessel size should be assessed after the intracoronary administration of nitroglycerin and the restoration of adequate coronary blood flow.

  • Recent studies have confirmed that the use of newer generation drug-eluting stents (DESs) in STEMI patients is safe, and that these reduce the need for target lesion and vessel revascularization at follow-up.10,11 Interestingly, the rates of stent thrombosis were significantly reduced with the use of DESs compared with bare-metal stents (BMSs), which could be due to a higher biocompatibility of newer permanent or biodegradable polymers compared with metallic surfaces, especially in the early healing phase after stent implantation.

  • The recommended duration of dual antiplatelet therapy (DAPT) after STEMI is 12 months; however, newer data suggest that a DAPT period of 6 months could be sufficient.12

In contrast to the management of STEMI patients, the benefit of PCI in non-ST-elevation myocardial infarction (NSTEMI) patients depends essentially on adequate patient selection.13 Generally, risk stratification relies on clinical parameters, electrocardiography and troponins (Figure 2). The higher a patient's ischaemic risk, the more he or she potentially benefits from an invasive approach. The web-based risk score calculator produced by GRACE (the Global Registry of Acute Coronary Events; available at www.outcomes-umassmed.org) facilitates clinical decision-making and interprofessional communication. On the other hand, the patient's ischaemic risk must be balanced against his or her bleeding risk. To this end, another web-based calculator, the CRUSADE Bleeding Score (www.crusadebleedingscore.org), helps to identify patients with a high bleeding risk. As the patients with a higher risk of bleeding complications tend to be those with a high risk of ischaemic events, appropriate measures to reduce the risk of bleeding have to be met in the NSTEMI setting. These include a transradial approach to PCI and cautious use of anticoagulants. Glycoprotein IIb/IIIa inhibitors should be reserved for emergency situations. As in the STEMI setting, it has been shown that the use of DESs can significantly reduce the need for target vessel and lesion revascularization compared with BMSs in patients who can tolerate DAPT for at least several months.

FIGURE 2

Decision-making algorithm in ACS. Reproduced with permission of Oxford University Press (UK) © European Society of Cardiology www.escardio.org/guidelines. Hamm CW, Bassand, JP, Agewall S, et al. ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: the Task Force for the management of acute coronary syndromes (ACS) in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J 2011; 32:2999–3054.13

6-1-13-fig2.jpg

Percutaneous coronary intervention strategies for stable patients with coronary artery disease

In contrast to the clear benefits of emergency PCI in ACS patients, the merits of PCI compared with optimal medical therapy in stable patients are less well established. Two landmark trials have failed to show a survival benefit for PCI-treated patients compared with those receiving optimal medical management.14,15 Although symptom reduction was better achieved in the PCI arms of these studies, this benefit did not last over a period of years. As neither trial reflects contemporary practice (e.g. DES use was negligible), the role of PCI in the setting of stable CAD is again being tested in the ongoing ISCHEMIA trial (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches; ClinicalTrials.gov identifier: NCT01471522).

Meanwhile, several important considerations must taken into account. The COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation; ClinicalTrials.gov identifier: NCT00007657) nuclear substudy16 has shown that the extent of myocardial ischaemia correlates with prognosis, and that PCI is performing better than optimal medical therapy in reducing the load of ischaemia. Therefore, the purpose of PCI is to reduce myocardial ischaemia and, in turn, the risk to the myocardium, as the severity of a coronary stenosis is one of the strong predictors of subsequent major adverse cardiac events arising from this site.17 This is also reflected by current guidelines (Table 1).18

TABLE 1

Indications for revascularization in stable angina or silent ischaemia. Adapted from Wijns W, Kohl P, Danchin N et al. Guidelines on myocardial revascularization. Eur Heart J 2010; 31:2501–55.18

Subset of CAD by anatomy Class Level
For prognosis
Left main > 50%a I A
Any proximal LAD > 50%a I A
2VD or 3VD with impaired LV functiona I B
Proven large area of ischaemia (> 10% LV) I B
Single remaining patent vessel > 50% stenosisa I C
1VD without proximal LAD and without > 10% ischaemia III A
For symptoms
Any stenosis > 50% with limiting angina or angina equivalent, unresponsive to OMT I A
Dyspnoea/CHF and > 10% LV ischaemia/viability supplied by > 50% stenotic artery IIa B
No limiting symptoms with OMT III C

a With documented ischaemia or FFR < 0.80 for angiographic diameter stenoses 50–90%. CAD = coronary artery disease; CHF = chronic heart failure; FFR = fractional flow reserve; LAD = left anterior descending; LV = left ventricle; OMT = optimal medical therapy; VD = vessel disease.

When dealing with patients with stable CAD, the treatment strategy must be based mainly on the severity of symptoms, extent of ischaemia, response to medical therapy and comorbidities. Where the results of non-invasive cardiac imaging are unclear, the determination of fractional flow reserve (FFR) has emerged as the gold standard19 for assessing the physiological significance of a stenosis in the catheterization laboratory (Figure 3). This combines the most relevant parameters modulating myocardial coronary blood flow in a fast and simple way, and guides PCI in a robust and reproducible manner.

FIGURE 3

Schematic principles of FFR and the influence of myocardial mass before and after myocardial infarction.19 FFR = Pd/Pa (≤ 0.80 = physiologically significant stenosis under maximal hyperaemia).19 FFR = Pd/Pa (≤ 0.80 = physiologically significant stenosis under maximal hyperaemia). Reprinted from J Am Coll Cardiol, vol. 59, Pijls NH, Sels JW, Functional measurement of coronary stenosis, pp. 1045–57, 2012, with permission from Elsevier.19

6-1-13-fig3.jpg

For instance, severe coronary triple-vessel disease assessed visually, or by other solely quantitative methods based on coronary angiography or intravascular imaging, can often be redefined as single- or two-vessel disease.20 The generally accepted cut-off value for the physiological significance of a coronary stenosis (FFR ≤ 0.80) has been shown to be robust in numerous studies not only when deferring PCI but also in forecasting future coronary events.21,22 The recently published FAME II trial (Fractional Flow Reserve-Guided Percutaneous Coronary Intervention Plus Optimal Medical Treatment Versus Optimal Medical Treatment Alone in Patients with Stable Coronary Artery Disease; ClinicalTrials.gov identifier: NCT01132495), carried out in patients with significant coronary stenoses as determined by FFR, reported that the risk of requiring unplanned urgent revascularization because of unstable angina or ACS was more than 10-fold higher among those who were randomized to optimal medical management, than among those who were treated using PCI. Further, one has to acknowledge that in patients with stable CAD, the use of FFR not only reduces unnecessary interventions but also helps to identify stenoses that, though appearing moderate, are haemodynamically significant. In particular, the severity of long coronary lesions is regularly underestimated by visual examination alone.

Although intravascular imaging techniques play a minor role in determining the significance of coronary stenoses in most catheterization laboratories, they play an important role in guiding complex PCI. Intravascular ultrasound (IVUS) guidance for PCI has proved superior to angiographic guidance alone in most studies;23 however, in the absence of a large randomised controlled trial, the level of recommendation for IVUS for left main interventions is only moderate in recent guidelines.18 The lack of large data sets may be partly explained by the difficulties inherent in deducing standardized PCI strategies based on potential IVUS findings. Although the associations between stent thrombosis and edge dissections, stent underexpansion/malapposition and residual-edge stenosis or atherosclerotic burden have been shown in older series,24 the detection of these is sometimes hampered by the relatively low resolution of images generated by IVUS. The introduction in clinical practice of Fourier-domain optical coherence tomography (FD-OCT), with an image resolution 10-fold higher than that of IVUS, has made it easier to assess these findings after coronary stenting. In the recent multicentre, non-randomized CLI-OPCI (Centro per la Lotta contro l'Infarto-Optimisation of Percutaneous Coronary Intervention) study,25 OCT guidance with clearly defined suboptimal PCI results after stenting improved survival and reduced non-fatal myocardial infarction rates. The ILUMIEN I trial (Observational Study of Optical Coherence Tomography in Patients Undergoing Fractional Flow Reserve and Percutaneous Coronary Intervention Stage I; ClinicalTrials.gov identifier: NCT01663896), currently under way, will further elucidate the potential benefits of FD-OCT in PCI guidance. In addition, FD-OCT is a valuable tool in identifying the reasons for late stent thrombosis (Figure 4) and in characterizing plaque morphology.

FIGURE 4

Examples of FD-OCT in patients with very late stent thrombosis. (A) Malapposed stent struts with adherent thrombi (arrow). (B) In-stent neoatherosclerosis (arrows: a = small thrombi; b =  necrotic core; and, c = stent struts).

6-1-13-fig4.jpg

Although the safety of newer DESs has been markedly improved,26 late stent failure due to restenosis or stent thrombosis, especially in patients with diabetes, remains a serious concern. The recently published FREEDOM study27 (Future Revascularization Evaluation in Patients with Diabetes Mellitus: Optimal Management of Multivessel Disease, ClinicalTrials. gov identifier: NCT00086450) has emphasized the superiority of coronary artery bypass grafting (CABG) over PCI in diabetic patients with multivessel disease. As in the landmark SYNTAX trial (SYNergy Between PCI with TAXUS and Cardiac Surgery; ClinicalTrials.gov identifier: NCT00114972),28 the superiority of CABG was associated with the extent and severity of CAD and was not seen in patients with a SYNTAX score < 22. Several technologies now exist which attempt to overcome the problem of late stent failure. For example, the introduction of biodegradable vascular scaffolds (BVSs) for clinical use offers numerous potential advantages over DESs, particularly in the long term, as degradation of the scaffold eliminates some of the possible causes for late stent failure. In addition, BVSs potentially preserve normal vasomotion and do not impede positive remodelling processes. Future trials will examine the role of BVSs in clinical practice.

Conclusion

Percutaneous coronary intervention plays a major role in the modern management of patients with CAD. Although the benefits of PCI in the ACS setting are clearly established, its use in patients with stable CAD must be tailored to each individual's circumstances. Newer technologies are attempting to further improve the long-term safety and efficacy of PCI. However, the limitations of current PCI techniques, especially in diabetic patients with multivessel disease, must be taken into consideration when deciding the best treatment strategy for each patient.

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