Landmark randomized controlled trials have consistently shown no difference in death or myocardial infarction between patients with stable ischemic heart disease (SIHD) who are treated with optimal medications alone compared to those treated with revascularization, with either coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) [1‐3]. Despite this, there is wide regional variation in the use of coronary revascularization, suggesting the possible misuse of these invasive therapies [4, 5].

The appropriate use criteria for coronary revascularization were designed to assist physicians balance the potential benefits of revascularization against its potential harms [6, 7]. Organized jointly by six international cardiovascular societies, an expert panel used a modified Delphi process to categorize clinical scenarios into appropriate, uncertain and inappropriate indications for coronary revascularization [6, 7]. The rationale for the appropriate use criteria in identifying candidates for revascularization will be strengthened if one demonstrates a strong relationship between improved outcomes and revascularization decisions based on the appropriateness score. Arguably, the most important indication for revascularization in SIHD is reducing symptomatic angina and improving quality of life, given the equivalence between optimal medical therapy and revascularization in reducing hard clinical outcomes. To the best of our knowledge, there are no data on the relationship between the appropriateness of revascularization and its impact on quality of life.

Accordingly, our objective in this prospective cohort study was to address this gap in knowledge by evaluating changes in generic and cardiac-specific quality of life over one year in patients with documented SIHD based on non-emergent coronary angiography, comparing patients with revascularization versus those with medical therapy, stratified by their appropriateness scores.

This study was approved by the Institutional Research Ethics Boards at Sunnybrook Health Sciences Center at the University of Toronto. All enrolled patients provided informed consent to participate in the study.

During the 1 year of patient accrual, 761 consecutive patients were enrolled. Of these, 282 patients had either mild coronary disease or normal coronaries arteries. A further 54 (7.1%) patients could not be assigned an appropriateness score because they had missing data on a previous stress testing. Our final cohort consisted of 425 patients, with 295 (69.4%) patients treated with revascularization within 90 days of their index angiogram. Of these, 78 (26.4%) patients underwent CABG, with a mean delay of 16.7 days (median 10, interquartile range 0–29 days), while 217 (73.6%) underwent PCI, at a mean delay of 2.5 days (median 0, interquartile range 0–0 days).

Within the final cohort, 272 (64.0%) had appropriate indications for revascularization, while 57 (13.4%) had inappropriate indications, and 96 (22.6%) had uncertain indications respectively. All of the 57 patients who had inappropriate indications had single or double vessel disease without involvement of the LAD and 40.4% were asymptomatic. The majority (51 patients/89.4%) were patients who were receiving minimal or no anti-anginal medications, with low-risk findings on non-invasive testing and were either asymptomatic (n = 17) or minimally symptomatic with CCS 1–2 (n = 34). The remaining 6 inappropriate patients were all asymptomatic, and had either low-risk non-invasive findings and were on maximal anti-anginal medical therapy (n = 4), or intermediate findings with minimal/no medications (n = 2). In the appropriate indication category, 75% of the patients underwent revascularization. In contrast, 53% of the patients with inappropriate indications underwent revascularization. Of the 96 patients with uncertain indications, 62% underwent revascularization.

The baseline characteristics for the cohort are shown on Table 1. Only 19.8% of patients were asymptomatic, with CCS 0 angina. Of the 425 patients in the cohort, 44.2% had single vessel disease, with 31.3% having double vessel disease and 24.6% having either triple vessel or left main artery disease. As expected, there were substantial differences between appropriateness categories in terms of the distribution of symptoms and anatomy, given that these are components of the appropriate use criteria. There were no statistically significant differences in the distribution of LV function. Only 26.1% of the overall cohort were on maximal anti-anginal therapy. The use of statin, β-blockers and ACE inhibitor/ARB medications were high among the cohort, with no differences between appropriateness groups (Table 1). Over a 1- year follow-up period mortality after the index angiogram was 2.6%; 9.9% of the cohort had a repeat MI within 1 year, while 10.4% underwent repeat PCI/CABG within 1 year. There were no differences among the three appropriateness categories in these outcomes; however, patients who were vascularized had a lower unadjusted mortality, but higher rates of both readmission for MI and repeat revascularization.

We found that the majority of patients with significant SIHD who underwent coronary angiography had appropriate indications for revascularization. Approximately three quarters of these patients underwent subsequent revascularization. Most patients had improvements in their self-reported quality of life in the first year after coronary angiography. Although patients with appropriate indications for revascularization derived greater improvements with revascularization compared to medical therapy, improvements were also seen for revascularized patients with uncertain and inappropriate indications, albeit in fewer quality of life sub-categories. However, these findings were not robust in sensitivity analyses that accounted for missing data with multiple imputations, and were most apparent in patients who underwent CABG, as opposed to those who were revascularized with PCI. Although appropriate use criteria appear to identify appropriate candidates for revascularization, our study raises doubts as to the utility of these criteria in excluding patients who are not candidates for revascularization.

There has been substantial interest in the development for appropriate use criteria for diagnostic tests and therapies, particularly in cardiovascular disease [11‐13]. These appropriate use criteria are developed through the expert consensus, and as such it is important to evaluate if the criteria translate into improved outcomes. Previous work from our group has validated the appropriateness criteria for revascularization by demonstrating that in SIHD patients who have appropriate indications, medical therapy was associated with worse outcomes when compared to revascularization, with a 39% increased hazard of death or repeat myocardial infarction over 3 years of follow-up [14]. Moreover, we found that revascularization was underutilized, with about 30% of patients with appropriate indications not receiving revascularization [14]. However, we did not find worse outcomes in revascularized patients who had uncertain or inappropriate indications, a finding consistent with other studies [14, 15]. We extend this previous work in the current study by evaluating the impact of under and overutilization of coronary revascularization on quality of life.

Quality of life is increasingly used as a patient-centered endpoint in cardiovascular disease studies, especially in SIHD, where invasive therapy is indicated for the relief of symptoms [16, 17]. In the landmark Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial, both patients treated with optimal medical therapy and those revascularized with PCI, had marked improvements in their quality of life as measured on the SAQ [18]. Patients who were treated with PCI had small incremental benefits over medical therapy, which was most prominent in the patient subgroup with more severe angina symptoms at baseline [18]. This is consistent with other evidence that has shown that the most important predictor of quality of life improvements post PCI is the severity of baseline angina [19]. Our study adds to these previous findings. Similar to the COURAGE trial, we found that the majority of patients tended to have improvements in quality of life. The greater benefit associated with revascularization compared to medical therapy seen in our study, in contrast to the COURAGE trial, maybe related to the relatively low proportion of patients in our cohort who on maximum anti-anginal therapy.

In patients with appropriate indications, we have reinforced the validation of the appropriate category, given the improved quality of life we observed for patients treated with revascularization who had appropriate indications. In combination with our previous work showing improved clinical outcomes for these patients with revascularization, this supports the use of the appropriate use criteria in identifying suitable candidates for revascularization.

The interpretation of the quality of life changes in the uncertain and inappropriate categories is complex. The rationale underlying the inappropriate indication category is that revascularization in these patients should not be of any benefit at all, and potentially harmful because these patients have minimal chest pain and good baseline function. However, despite the relatively small number of patients in these categories, we found that revascularization in patients with both uncertain and inappropriate criteria appeared to have greater improvements in quality of life in some of the SAQ sub-categories when compared to medical therapy. This suggests the appropriate use criteria may need greater refinement in order to better exclude patients who are indeed poor candidates for revascularization. The lack of discrimination for the appropriateness guidelines for clinical benefit may relate to the inclusion of symptomatic patients in the inappropriate category. Indeed, of the 57 patients with inappropriate indications, 60% had symptoms. Potential refinements may be the inclusion of quality of life as measured on instruments such as the SAQ, as opposed to CCS class, in order to better identify patients with minimal symptoms who would not benefit from revascularization.

Our study must be interpreted in the context of several limitations that merit discussion. First, despite our best efforts, a considerable portion of enrolled patients did not complete all the quality of life surveys. We evaluated the impact of missing data in the sensitivity analyses through multiple imputations. Although it is reassuring that the qualitative direction of our results were maintained, the comparisons between treatment strategies within appropriateness categories were not longer statistically significant. Second, our analysis was restricted to patients who survived at least a year after their index coronary angiogram. This limitation is mitigated by the fact that we were evaluating a SIHD population and therefore, we would not expect a high mortality rate. In addition, it is notable that only approximately a quarter of our patients were on optimal medical therapy, reflecting the inadequacy of routine medical care in real world practice. Our cohort consisted of patients recruited at a single, large tertiary academic hospital in Ontario, Canada. Indeed, previous work from our group suggests that there maybe a higher threshold for invasive testing in Canada, and as such our results may not be generalizable to other jurisdictions or patient populations [4]. We were limited in the anatomical data available to the location of the lesions. Although this was sufficient to assign patients to appropriateness categories, we were not able to account for the complexity of anatomy, such as the presence of calcification or bifurcation status which may have impacted the decision to revascularize. Finally, this is an observational study designed to evaluate associations between treatment strategy, appropriate use criteria and outcomes. We cannot establish causality, and so our work should be considered hypothesis generating and not conclusive. We believe that our results reinforce the need for an adequately powered randomized trial to evaluate the benefit of determining treatment strategy based on appropriate use criteria.

In conclusion, we found that coronary revascularization is associated with greater improvements in quality of life compared to medical therapy, in particular in patients with appropriate indications. However, refinements are needed in the appropriate use criteria to better exclude patients who would not derive benefit from revascularization.

The specific contributions of the authors are outlined below: HCW: 1) conception, design, analysis and interpretation of data; 2) drafting of the manuscript; and 3) final approval of the manuscript submitted. FQ: 1) analysis and interpretation of data; 2) revising the manuscript critically for important intellectual content; and 3) final approval of the manuscript submitted. PF: 1) conception and design; 2) revising the manuscript critically for important intellectual content; and 3) final approval of the manuscript submitted. MCB: 1) analysis and interpretation of data; 2) revising the manuscript critically for important intellectual content; and 3) final approval of the manuscript submitted. PCA: 1) analysis and interpretation of data; 2) revising the manuscript critically for important intellectual content; and 3) final approval of the manuscript submitted. DTK: 1) conception, design, analysis and interpretation of data; 2) revising the manuscript critically for important intellectual content; and 3) final approval of the manuscript submitted.