Towards Evidence-Based Percutaneous Coronary Intervention
Why should patients with stable coronary artery disease fail to accrue prognostic benefit from PCI? This may, at least in part, be related to the fact that the highest risk patients (who arguably stand to benefit the most from revascularization) are often excluded from these trials. Patients with 'a markedly positive stress test' were excluded from the COURAGE trial, whereas patients with left main stem lesions were excluded from the BARI-2D study. Yet, patients from both of these trials were not at particularly low risk, so selection of low risk patients cannot account for the failure of routine PCI in these trials to improve outcomes. 'Significant' coronary artery stenosis, as defined by coronary angiography, was a major inclusion criterion of all of these trials. Coronary angiography is a poor assessor of the extent and severity of actual coronary artery disease when compared with autopsy or intravascular ultrasound. In addition, there is only a weak correlation between angiographically determined coronary stenosis severity and functional significance. We also know that the majority of coronary plaques responsible for acute MI are non-flow limiting with 132 out of 194 culprit plaques having a stenosis less than 50% in one series. However, a natural history study of plaque progression suggested that a minimal luminal area less than 4 mm was one of three factors independently associated with future adverse events. Nonetheless, PCI in stable angina patients may not confer prognostic benefit because we may not be stenting the right lesions. It would appear more logical and potentially beneficial to focus on lesions that are either responsible for large areas of ischaemia or are likely to result in MI. The former can be assessed by either non-invasive imaging or measurement of fractional flow reserve (FFR) (because FFR is related both to the degree of stenosis as well as to the size of myocardium at risk). However, identifying which plaques are likely to result in MI is more challenging. Natural history studies using virtual histology intravascular ultrasound (VH-IVUS) to identify thin-capped fibroatheroma (TCFA) suggest that they are associated with increased MACE rates compared with other plaques (HR = 3.35, P < 0.001) and (HR = 7.53, P = 0.036). However, the limited axial resolution of VH-IVUS of 150 μm is insufficient to identify the 65 μm limit of the histology-identified TCFA that is responsible for 70% of thrombotic vessel occlusion in sudden cardiac death. Thus, VH-IVUS overestimates the number of TCFA and hence it is unlikely that prophylactically stenting these lesions will reduce MACE. Although optical coherence tomography does have sufficient resolution (15 μm), no natural history studies are, as yet, forthcoming. Therefore, PCI is an effective (and relatively safe) treatment for potentially dangerous coronary artery plaques but we do not yet know how to reliably identify these.
Failure of Percutaneous Coronary Intervention to Improve Clinical Outcomes in Patients With Stable Coronary Artery Disease: A Matter of the Wrong Target?
Why should patients with stable coronary artery disease fail to accrue prognostic benefit from PCI? This may, at least in part, be related to the fact that the highest risk patients (who arguably stand to benefit the most from revascularization) are often excluded from these trials. Patients with 'a markedly positive stress test' were excluded from the COURAGE trial, whereas patients with left main stem lesions were excluded from the BARI-2D study. Yet, patients from both of these trials were not at particularly low risk, so selection of low risk patients cannot account for the failure of routine PCI in these trials to improve outcomes. 'Significant' coronary artery stenosis, as defined by coronary angiography, was a major inclusion criterion of all of these trials. Coronary angiography is a poor assessor of the extent and severity of actual coronary artery disease when compared with autopsy or intravascular ultrasound. In addition, there is only a weak correlation between angiographically determined coronary stenosis severity and functional significance. We also know that the majority of coronary plaques responsible for acute MI are non-flow limiting with 132 out of 194 culprit plaques having a stenosis less than 50% in one series. However, a natural history study of plaque progression suggested that a minimal luminal area less than 4 mm was one of three factors independently associated with future adverse events. Nonetheless, PCI in stable angina patients may not confer prognostic benefit because we may not be stenting the right lesions. It would appear more logical and potentially beneficial to focus on lesions that are either responsible for large areas of ischaemia or are likely to result in MI. The former can be assessed by either non-invasive imaging or measurement of fractional flow reserve (FFR) (because FFR is related both to the degree of stenosis as well as to the size of myocardium at risk). However, identifying which plaques are likely to result in MI is more challenging. Natural history studies using virtual histology intravascular ultrasound (VH-IVUS) to identify thin-capped fibroatheroma (TCFA) suggest that they are associated with increased MACE rates compared with other plaques (HR = 3.35, P < 0.001) and (HR = 7.53, P = 0.036). However, the limited axial resolution of VH-IVUS of 150 μm is insufficient to identify the 65 μm limit of the histology-identified TCFA that is responsible for 70% of thrombotic vessel occlusion in sudden cardiac death. Thus, VH-IVUS overestimates the number of TCFA and hence it is unlikely that prophylactically stenting these lesions will reduce MACE. Although optical coherence tomography does have sufficient resolution (15 μm), no natural history studies are, as yet, forthcoming. Therefore, PCI is an effective (and relatively safe) treatment for potentially dangerous coronary artery plaques but we do not yet know how to reliably identify these.
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