This editorial refers to ‘The incidence and relevance of site-reported vs. patient-reported angina: insights from the ABSORB II randomized trial comparing Absorb everolimus-eluting bioresorbable scaffold with XIENCE everolimus-eluting metallic stent’, by M.J. Grundeken et al., on page 108.

Percutaneous coronary intervention (PCI) is an important form of revascularization therapy that has potential benefits but also significant risks. In patients with an acute coronary syndrome presentation, the risks of a major adverse cardiac event (MACE—i.e. death and myocardial infarction) are substantial and improved with early intervention, so that the benefits outweigh the risks.1,2 Accordingly, the use of PCI in acute coronary syndrome is readily justified and is reflected in appropriateness use criteria.3

In contrast, patients with stable coronary artery disease (CAD) have a low risk of MACE and several studies have confirmed that PCI does not reduce the risk of MACE in these patients.4,5 Whether the selection of a high-risk stable CAD cohort (i.e. those with significant CAD and a documented moderate zone of ischaemia) for PCI will result in an improvement in MACE is the focus of the ongoing ISCHEMIA trial.6 In the interim, the benefits of PCI in patients with stable CAD need to focus on symptomatic improvement rather than a reduction in cardiac events.

Benefits of percutaneous coronary intervention in stable coronary artery disease

Clinical efficacy studies of PCI in patients with stable CAD have demonstrated an incremental benefit of alleviating angina symptoms over medical therapy. The most influential and contemporary of these randomized controlled trials is a sub-study of the COURAGE trial. In this investigation, Weintraub et al.7 demonstrated a small incremental benefit of PCI over optimal medical therapy alone in alleviating angina, although this treatment difference was lost over the next 36 months. Importantly, these findings are translatable to a ‘real-world’ scenario, as evident by clinical registry data,8 thereby also confirming the clinical effectiveness of PCI in reducing angina frequency (Figure 1). Accordingly, PCI for stable CAD should be considered in patients who are not satisfactorily controlled with optimal medical therapy, as reflected in current guidelines9 and appropriateness use criteria.3

Figure 1

Post-percutaneous coronary intervention angina as assessed by the Seattle Angina Questionnaire for patients in the COURAGE Trial compared with a Hospital Registry. Angina frequency assessed by the Seattle Angina Questionnaire in the COURAGE trial (red lines) for percutaneous coronary intervention + optimal medical therapy (solid red line) and optimal medical therapy alone (dashed red line) when compared with the ‘real-world experience’ from an Australian hospital (The Queen Elizabeth Hospital—TQEH, in green) for percutaneous coronary intervention (solid green line) and medical therapy (dashed green line). Adapted from Beltrame et al.8

Figure 1

Post-percutaneous coronary intervention angina as assessed by the Seattle Angina Questionnaire for patients in the COURAGE Trial compared with a Hospital Registry. Angina frequency assessed by the Seattle Angina Questionnaire in the COURAGE trial (red lines) for percutaneous coronary intervention + optimal medical therapy (solid red line) and optimal medical therapy alone (dashed red line) when compared with the ‘real-world experience’ from an Australian hospital (The Queen Elizabeth Hospital—TQEH, in green) for percutaneous coronary intervention (solid green line) and medical therapy (dashed green line). Adapted from Beltrame et al.8

Establishing post-percutaneous coronary intervention angina in stable coronary artery disease as a performance measure

Since the major benefit of PCI in stable CAD is to alleviate angina symptoms, it is paramount to monitor this endpoint both in relation to optimizing quality healthcare and value, as well as providing a benchmark for new innovations in PCI; consequently, ‘post-PCI angina’ has been proposed as a new performance measure.10

The frequency of 12-month post-PCI angina for stable CAD has been variably reported as ∼20–40% in randomized controlled trials, but may be higher in real-world clinical practice. The mechanisms responsible for the ongoing angina may include suboptimal stenting, in-stent restenosis, residual CAD not amenable to revascularization, vasospastic angina, coronary microvascular dysfunction, or non-coronary causes of the chest pain. Routine monitoring of post-PCI angina will provide the foundation for an improved understanding of this clinically relevant endpoint, as well as fostering the evolution of novel approaches to improve this symptom and therefore the outcomes of elective PCI.

To develop post-PCI angina as a performance marker, it is important to standardize its measurement since this may contribute to the apparent variability between studies. This is highlighted by the study from Grundeken et al.11 in this issue of the Journal, where different approaches in angina assessment resulted in different findings. In this investigation, the authors evaluate ‘site-reported angina’ as a measure of post-PCI angina in the ABSORB-II trial. This approach is dependent on adverse event reporting from the participating clinical trial sites and utilizes a cumulative angina analysis approach, where one or more episodes of angina following PCI categorizes the patient as post-PCI angina-positive. Using this ‘site-reported angina’ methodology to dichotomize patients, the authors demonstrate that those with post-PCI angina at 12 months have more cardiac events, positive stress tests, and cardiovascular resource utilization than those without symptoms. Moreover, utilizing this methodology in this post hoc subanalysis demonstrated less post-PCI angina in patients randomized to the Absorb BVS stent deployment when compared with those who had the XIENCE EES drug-eluting stent. This finding contrasts to the published result in the main ABSORB-II trial study12 where no difference in post-PCI angina was observed between stents when the endpoint was assessed by the well-established and validated Seattle Angina Questionnaire. The authors conclude that cumulative analysis of site-reported post-PCI angina via adverse event reporting is clinically relevant and speculate that there are problems with the traditional approach of cross-sectional analysis at specific time points since angina episodes may be missed if outside the 4-week sampling period with the latter approach. These two approaches will be further assessed in the current ABSORB-III and IV trials.

Interpreting the findings of Grundeken et al.'s study is difficult considering its significant limitation including post hoc analysis of a single-blind study, ad hoc adverse event reporting with the potential for variability between sites, no rigorous criteria for post-PCI angina, and dependence on clinician- rather patient-reported angina. Moreover, the associations used to validate the site-reported angina may be interdependent with the measured endpoints of cardiac events, stress testing, and resource utilization. Irrespective of these limitations, the study serves to incite discussion regarding the optimal criteria for post-PCI angina.

Table 1 summarizes the issues that need to be considered in establishing post-PCI angina as a performance measure. The first issue relates to the data source, which preferably should be directly obtained from the patient, as they are the only person who experiences the symptoms. Thus, many studies utilize patient-reported outcome measures, whereas others utilize clinician questioning of patients. Comparisons of these approaches demonstrate that clinician reporting of angina underestimates patient-reported angina.13

Table 1

Considerations in establishing post-PCI angina criteria

Post-PCI angina criteria Potential approaches 
Data source • Patient-reported angina: direct patient questioning (gold standard).• Clinician-reported angina: dependent on clinician interpretation of symptoms. 
Data collection methods • Continuous angina monitoring: via angina diaries, smart phone apps, and adverse event reporting.• Discrete time point monitoring: typically recorded at 1, 6, and 12 months following PCI, with reporting of status over the preceding 4 weeks. 
Data analysis • Cumulative angina analysis: post-PCI angina analysis on the basis of one or more episodes during the entire reporting time interval.• Cross-sectional angina analysis: post-PCI angina analysis on the basis of one or more episodes during the discrete time point sample period (i.e. 4-week period). 
Reporting time frame • 12-month post-PCI angina: conventional time period assessed.• 6-month post-PCI angina: greatest improvement in angina, especially in the first 30 days (Figure 1). Also, a key time interval for in-stent restenosis. 
Health impact • Canadian Cardiovascular Society Classification: clinician-reported, semi-quantitative classification (Class I–IV angina) reflecting impact on physical functioning.• Quality of life questionnaires (e.g. Short Form-36): validated, generic quality-of-life instruments enabling comparisons with other medical conditions.• Health status questionnaires (e.g. Seattle Angina Questionnaire): validated, disease-specific instruments assessing angina frequency, disease-related physical limitations, and disease-related quality of life. 
Post-PCI angina criteria Potential approaches 
Data source • Patient-reported angina: direct patient questioning (gold standard).• Clinician-reported angina: dependent on clinician interpretation of symptoms. 
Data collection methods • Continuous angina monitoring: via angina diaries, smart phone apps, and adverse event reporting.• Discrete time point monitoring: typically recorded at 1, 6, and 12 months following PCI, with reporting of status over the preceding 4 weeks. 
Data analysis • Cumulative angina analysis: post-PCI angina analysis on the basis of one or more episodes during the entire reporting time interval.• Cross-sectional angina analysis: post-PCI angina analysis on the basis of one or more episodes during the discrete time point sample period (i.e. 4-week period). 
Reporting time frame • 12-month post-PCI angina: conventional time period assessed.• 6-month post-PCI angina: greatest improvement in angina, especially in the first 30 days (Figure 1). Also, a key time interval for in-stent restenosis. 
Health impact • Canadian Cardiovascular Society Classification: clinician-reported, semi-quantitative classification (Class I–IV angina) reflecting impact on physical functioning.• Quality of life questionnaires (e.g. Short Form-36): validated, generic quality-of-life instruments enabling comparisons with other medical conditions.• Health status questionnaires (e.g. Seattle Angina Questionnaire): validated, disease-specific instruments assessing angina frequency, disease-related physical limitations, and disease-related quality of life. 

PCI: percutaneous coronary intervention; CAD: coronary artery disease.

Although some stable CAD studies utilize only a single approach for angina monitoring, many adopt both continuous and discrete time point angina monitoring data collection methods (e.g. ABSORB-II). This enables data analysis (Table 1) to be undertaken either by cumulative or by cross-sectional angina analysis. Each of these approaches have their merits and limitations, with data collection burden being a significant problem for continuous monitoring and the risk of missing important angina episodes for the discrete time monitoring. Further research is required to explore the optimal approach in undertaking monitoring/analysis (whether one or both approaches) and interpreting the findings should the analyses be in conflict.

Most stable CAD studies use a reporting time frame (Table 1) of 12-month post-PCI angina, which places significant burden on data capture, especially if continuous angina monitoring is desired. Whether 6-month post-PCI angina provides sufficient data as a performance measure requires further evaluation. Certainly, this time frame captures most of the improvement observed following PCI (as shown in Figure 1) and would reduce the data capture burden.

The health impact (Table 1) of stable CAD is also important to assess since some patients may experience frequent episodes of angina that has only minimal impact on their lifestyle, whereas others may be severely disabled by fewer episodes. The health impact is typically assessed at discrete time intervals and may employ simple clinical measures (e.g. Canadian Cardiovascular Society Classification), generic health instruments (e.g. Short Form-36), or a comprehensive disease-specific health status instrument (e.g. Seattle Angina Questionnaire). In some studies, all three approaches may be adopted, but this needs to be tempered with the data collection burden.

In summary, post-PCI angina is an important performance measure that needs to be established to ensure quality care and provide insights into the appropriateness of PCI in patients with stable CAD. Furthermore, this should be a measure of the clinical efficacy and effectiveness for new PCI innovations, thereby optimizing value healthcare. The optimal criteria for post-PCI angina require further evaluation and establishment by professional societies.

Conflict of interest: Dr Beltrame reports grants from AstraZeneca, outside the submitted work.

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Author notes

The opinions expressed in this article are not necessarily those of the Editors of the European Heart Journal – Quality of Care and Clinical Outcomes or of the European Society of Cardiology.