Results

Patients in the ACRE cohort had a median (range) age of 61 (21–89) years and 29% were women (table 1). Twenty four per cent had previously undergone coronary angiography.

Table 2 shows the clinical presentation for which patients underwent coronary angiography. Clinical presentation was defined as chronic stable angina (n = 1431, 39% of the cohort), unstable angina (n = 568, 16%), acute myocardial infarction (n = 216, 6%), postmyocardial infarction (n = 167, 5%), post-revascularisation (n = 529, 15%), asymptomatic (n = 154, 4%), atypical chest pain (n = 175, 5%) near sudden death or ventricular arrhythmia (n = 70, 2%), and miscellaneous (n = 321, 9%). Exercise ECG was performed in 47% overall (table 1), although this varied by clinical presentation: chronic stable angina class I/II (70%), chronic stable angina class III/IV (60%), unstable angina (30%), acute myocardial infarction (14%), post-myocardial infarction (39%), postrevascularisation (44%), asymptomatic (84%), atypical chest pain (75%), near sudden death (32%), ventricular arrhythmia (54%), and miscellaneous (4%).

Figure 1 shows that of the 2178 indications that were rated by the expert panel, only 241 (11.1%) were actually represented by the patients; a subset of 43 indications described 75% of the patient sample.

Overall, 166 (5%) of coronary angiograms were performed for indications rated inappropriate, 1212 (33%) uncertain, and 2253 (62%) appropriate. The panellists rated 436 indications as inappropriate; but only 166 patients (5%, represented by 39 indications) actually underwent angiography for inappropriate indications. Two clinical presentations—asymptomatic and atypical chest pain—comprised 73% of these inappropriate angiograms. The two most common uncertain clinical indications for coronary angiography (comprising 47% of the uncertain group) were patients with mild angina and no exercise ECG or patients with unstable angina controlled by inpatient management.

Table 3 shows the graded association between appropriateness categories and the number of diseased vessels at angiography. Patients who had had a previous revascularisation, and therefore were known to have CAD, were excluded from this analysis. The proportion of angiograms showing three vessel or left main stem disease was highest in the appropriate group (n = 458, 25%), intermediate in the uncertain category (n = 187, 18%), and lowest in the inappropriate category (n = 16, 11%) (p value for heterogeneity < 0.001).

The ability of appropriateness categories to predict the presence or absence of CAD was compared with the Duke score and result of the exercise ECG among 1317 patients with complete covariates for each of the three measures. The sensitivities were 779 of 967 (81%) for appropriate compared with not appropriate (uncertain and inappropriate), 831 of 967 (86%) for a Duke score in the top four quintiles, and 755 of 967 (78%) for a positive exercise ECG. The corresponding specificities were 119 of 350 (34%), 149 of 350 (43%), and 145 of 350 (41%), respectively.

The rate of all cause mortality was strongly related to the appropriateness of the angiogram (fig 2). Mortality was highest among patients undergoing angiography for appropriate indications, intermediate in the uncertain group, and lowest in the inappropriate group (logrank p = 0.018). The proportions of patients who died were 151 of 2253 (6.7%), 67 of 1211 (5.5%), and 8 of 166 (4.8%), respectively. In patients undergoing angiography for appropriate compared with those undergoing angiography for inappropriate indications, the hazard ratio for mortality was 1.75 (95% CI 0.9 to 3.6). These findings were consistent for coronary mortality (1.53, 95% CI 0.6 to 3.8; logrank p = 0.025), and cardiovascular mortality (2.08, 95% CI 0.8 to 5.1; logrank p = 0.0128).

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Figure 2

All cause mortality after angiography, by appropriateness category.

The rate of revascularisation among those with CAD was also strongly related to the appropriateness of the angiogram. The revascularisation rate was highest among patients undergoing angiography for appropriate indications, intermediate in the uncertain group, and lowest in the inappropriate group (logrank p < 0.0001). The proportions of patients undergoing revascularisation were 1035 of 1676 (62%), 451 of 822 (54%), and 39 of 95 (41%), respectively. In patients undergoing angiography for appropriate compared with those undergoing angiography for inappropriate indications, the hazard ratio for revascularisation was 1.76 (95% CI 1.3 to 2.5). Figures 3 (PTCA) and 4 (CABG) show that the association of appropriateness category with subsequent revascularisation was confined to CABG. The hazard ratio for CABG in appropriate compared with inappropriate indications was 2.21 (95% CI 1.4 to 3.4), logrank p < 0.0001.

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Figure 3

Percutaneous transluminal coronary angioplasty (PTCA) after angiography, by appropriateness category.

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Figure 4

Coronary artery bypass grafting (CABG) after angiography, by appropriateness category.

Discussion

In a cohort without exclusion criteria of over 3000 patients undergoing coronary angiography followed up for 2.5 years, the ACRE ratings of appropriateness predicted the number of diseased vessels, survival, and subsequent revascularisation. Rates were highest in patients undergoing angiography for appropriate indications, intermediate in those with an uncertain indication, and lowest in the inappropriate group. Although many previous expert panels have rated angiography appropriateness, none has prospectively shown such clinical validity. The applicability of this method in routine practice is further enhanced as the ACRE appropriateness ratings were tested in a cohort of angiography patients without exclusion criteria. For specific subsets of clinical indications, evidence, technology, and practice evolve rapidly and in these areas the ratings require refinement. However, expert panels provide the only validated method of systematically defining criteria for patients undergoing angiography, in which potential benefits are quantified.

Coronary angiography is performed to diagnose the presence and severity of CAD, to identify high risk patients, and thereby to determine the need for subsequent revascularisation. To determine the clinical relevance and validity of the appropriateness ratings, we therefore tested each of these three outcomes. Firstly, appropriateness ratings, if valid, should predict the number of diseased vessels. The hypothesis was confirmed: the three appropriateness categories showed a graded relation with the number of diseased vessels. Furthermore, the sensitivity and specificity of the appropriateness category in predicting CAD were as good as the exercise ECG or a multivariate score (from Duke) of other non-invasive predictors of CAD. Such relations have not previously been shown, although a small study showed that the presence of CAD was more likely in appropriate patients.13

Secondly, an angiogram performed for an appropriate indication should identify patients with high risk of mortality. This was confirmed. Since CABG may offer prognostic benefit in specific patient subgroups we censored the mortality follow up before revascularisation. We have previously reported how the expert panel ratings of coronary revascularisation appropriateness identified substantial underuse of these procedures; such underuse was associated with adverse clinical outcomes.16

The third test of clinical relevance was that appropriateness ratings should be associated with subsequent revascularisation rate, independent of any associations with the presence of CAD. As hypothesised, a graded association among the three appropriateness categories and revascularisation rate was seen among patients with CAD, with the lowest rate among those with inappropriate indications. This effect was striking for CABG, reflecting the association between the appropriateness of angiography and triple vessel and left main stem disease. These results are also consistent with the importance of anginal severity on maximal medication in determining the ACRE panel's ratings of appropriateness for angiography17 and in turn the importance of symptom severity in judging the need for revascularisation.

However, if the expert panel method defines indications for angiography in three clinically meaningful groups, the ratings require ongoing refinement to keep abreast of changes in evidence, technology, clinical practice, and patient expectation. Although results are based on small numbers, 11% of the inappropriate group did have triple vessel or left main stem disease and 22% of all patients undergoing angiography for inappropriate indications who had CAD were subsequently revascularised. These findings emphasise the importance of improving the rating process. It is an inherent feature of a prospective study with up to three years' follow up that some ratings do not remain current. The approach used in the ACRE study is well suited to making such refinements since it is able to quantify the frequency of specific clinical indications. For example, the trial evidence for primary angioplasty published after the expert panel met is likely to lead to more appropriate ratings for angiography in acute myocardial infarction. However, among all patients undergoing angiography this remains a much less common indication for angiography than chronic stable angina, where the evidence has changed less dramatically.

One third of the ACRE patients underwent angiography for indications rated as uncertain—that is, benefits and harms of angiography were balanced or there was insufficient evidence for the panel to judge either way. This uncertain group has been criticised by others, partly because clinical decision making is binary—a procedure is either done or not done. However, our data suggest that the judgement of “uncertain” does contribute predictive information: angiographic findings, mortality, and revascularisation rates were all intermediate between patients undergoing angiography for inappropriate and appropriate indications. The uncertain category may provide a systematic identification of areas for future research.

Appropriateness ratings may be used to determine overuse and underuse.16 Coronary angiography performed for indications rated as inappropriate may represent overuse and was found in 5% of patients. Coronary angiography carries a small but finite risk of major complication24 and is a costly procedure. Asymptomatic or atypical chest pain presentations accounted for over 70% of the inappropriate angiograms. Within these presentations, the specific indications that were rated as inappropriate showed close agreement with the latest recommendations in the American Heart Association/American College of Cardiology angiography guidelines.3 Three questions arise. Firstly, does the indication itself adequately define the patient or do new indications need to be formulated? For example, angiography may be indicated to reveal normal coronary arteries in patients frequently attending with atypical chest pain and a low pretest probability of CAD,25 ,26 yet the existing indication lists do not stipulate such indications. Secondly, does the rating of appropriateness reflect current evidence? Thirdly, if the indication adequately defines the patient and the rating remains evidence based, what changes in practice are required to prevent such inappropriate use in the future? It should not, however, be assumed that eradicating inappropriate use is desirable because it may be achieved at the cost of unacceptably high thresholds for investigation.

The ACRE findings do not suggest that there is significant overuse of angiography. However, a further test of their clinical validity is warranted in which the ratings are used to investigate underuse. US studies show higher proportions of underuse than of overuse.27 Future studies should use angiography appropriateness ratings in patients recruited at the time of first presentation and test the extent to which angiography was performed in patients with appropriate indications. The ACRE findings in relation to revascularisation strongly support assessing underuse with appropriateness ratings.16

There are no European guidelines on coronary angiography. The UK'sNational service framework for coronary heart disease 28 has set a standard that “people with symptoms of angina should receive appropriate investigation”. The ACRE cohort, recruited during the stenting era, is likely to be reasonably representative of UK practice because of its large geographically defined sample selected without exclusion criteria. Furthermore, expert panels show good agreement with practising physicians.29 Thus the ACRE ratings of appropriateness form a basis for articulating such government policy in order that primary and secondary care doctors, as well as cardiologists, meet the new national standards.

The unacceptably long waiting times for coronary angiography raise the question of the clinical ordering of the angiography queue in the NHS. However, simple relations between appropriateness and urgency should not be assumed.30 Appropriateness categories were related to waiting time but it was patients undergoing angiography for appropriate indications who had the longest wait (median time to angiography 91 days), compared with 58 days for inappropriate and 50 days for uncertain indications (logrank p = 0.02). Furthermore, the relation between waiting times was much stronger with a priori urgency scores than with appropriateness categories in the ACRE cohort.31

Potential limitations of the ACRE study should be considered. Firstly, like other studies of appropriateness, the ACRE study relied on clinical record data to infer why coronary angiography was performed. However, it has been shown that the written clinical records show excellent agreement with the performing physician when interviewed.32 Secondly, since the panel members rating appropriateness were recruited from the same institution as the cohort of patients, the study itself may have influenced practice. However, such a Hawthorne effect33 is unlikely because there was no relation between the proportion of appropriate patients and time since the expert panel met; over 80% of angiography procedures were performed by cardiologists who were not members of the expert panel and excluding panellists' procedures from the analysis made no difference to the results.

Patients undergoing angiography for appropriate indications had most CAD and the highest subsequent revascularisation and mortality rates, showing the prospective validity of the expert panel ratings. As the rate of angiography continues to increase, the use of such explicit criteria to improve the quality of care should be encouraged.