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GMS Health Technology Assessment

Deutsche Agentur für Health Technology Assessment (DAHTA)

ISSN 1861-8863

CT coronary angiography vs. invasive coronary angiography in CHD

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  • corresponding author Vitali Gorenoi - Institute for Epidemiology, Social Medicine and Health Systems Research, Hannover, Germany
  • author Matthias P. Schönermark - Institute for Epidemiology, Social Medicine and Health Systems Research, Hannover, Germany
  • author Anja Hagen - Institute for Epidemiology, Social Medicine and Health Systems Research, Hannover, Germany

GMS Health Technol Assess 2012;8:Doc02

doi: 10.3205/hta000100, urn:nbn:de:0183-hta0001009

This is the original version of the article.
The translated version can be found at: http://www.egms.de/de/journals/hta/2012-8/hta000100.shtml

Published: April 16, 2012

© 2012 Gorenoi et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.

The complete HTA Report in German language can be found online at: http://portal.dimdi.de/de/hta/hta_berichte/hta308_bericht_de.pdf


Outline

Abstract

Scientific background

Various diagnostic tests including conventional invasive coronary angiography and non-invasive computed tomography (CT) coronary angiography are used in the diagnosis of coronary heart disease (CHD).

Research questions

The present report aims to evaluate the clinical efficacy, diagnostic accuracy, prognostic value cost-effectiveness as well as the ethical, social and legal implications of CT coronary angiography versus invasive coronary angiography in the diagnosis of CHD.

Methods

A systematic literature search was conducted in electronic data bases (MEDLINE, EMBASE etc.) in October 2010 and was completed with a manual search. The literature search was restricted to articles published from 2006 in German or English. Two independent reviewers were involved in the selection of the relevant publications.

The medical evaluation was based on systematic reviews of diagnostic studies with invasive coronary angiography as the reference standard and on diagnostic studies with intracoronary pressure measurement as the reference standard. Study results were combined in a meta-analysis with 95 % confidence intervals (CI). Additionally, data on radiation doses from current non-systematic reviews were taken into account.

A health economic evaluation was performed by modelling from the social perspective with clinical assumptions derived from the meta-analysis and economic assumptions derived from contemporary German sources.

Data on special indications (bypass or in-stent-restenosis) were not included in the evaluation. Only data obtained using CT scanners with at least 64 slices were considered.

Results

No studies were found regarding the clinical efficacy or prognostic value of CT coronary angiography versus conventional invasive coronary angiography in the diagnosis of CHD.

Overall, 15 systematic reviews with data from 44 diagnostic studies using invasive coronary angiography as the reference standard (identification of obstructive stenoses) and two diagnostic studies using intracoronary pressure measurement as the reference standard (identification of functionally relevant stenoses) were included in the medical evaluation.

Meta-analysis of the nine studies of higher methodological quality showed that, CT coronary angiography with invasive coronary angiography as the reference standard, had a sensitivity of 96 % (95 % CI: 93 % to 98 %), specificity of 86 % (95 % CI: 83 % to 89 %), positive likelihood ratio of 6.38 (95 % CI: 5.18 to 7.87) and negative likelihood ratio of 0.06 (95 % CI: 0.03 to 0.10). However, due to non-diagnostic CT images approximately 3.6 % of the examined patients required a subsequent invasive coronary angiography.

Using intracoronary pressure measurement as the reference standard, CT coronary angiography compared to invasive coronary angiography had a sensitivity of 80 % (95 % CI: 61 % to 92 %) versus 67 % (95 % CI: 51 % to 78 %), a specificity of 67 % (95 % CI: 47 % to 83 %) versus 75 % (95 % CI: 60 % to 86 %), an average positive likelihood ratio of 2.3 versus 2.6, and an average negative likelihood ratio 0.3 versus 0.4, respectively.

Compared to invasive coronary angiography, the average effective radiation dose of CT coronary angiography was higher with retrospective electrocardiogram (ECG) gating and relatively similar with prospective ECG gating.

The health economic model using invasive coronary angiography as the reference standard showed that at a pretest probability of CHD of 50 % or lower, CT coronary angiography resulted in lower cost per patient with true positive diagnosis. At a pretest probability of CHD of 70 % or higher, invasive coronary angiography was associated with lower cost per patient with true positive diagnosis. Using intracoronary pressure measurement as the reference standard, both types of coronary angiographies resulted in substantially higher cost per patient with true positive diagnosis.

Two publications dealing explicitly with ethical aspects were identified. The first addressed ethical aspects regarding the principles of beneficence, autonomy and justice, and the second addressed those regarding radiation exposition, especially when used within studies.

Discussion

The discriminatory power of CT coronary angiography to identify patients with obstructive (above 50 %) coronary stenoses should be regarded as “high diagnostic evidence”, to identify patients without coronary stenoses as “persuasive diagnostic evidence”. The discriminatory power of both types of coronary angiography to identify patients with or without functionally relevant coronary stenoses should be regarded as “weak diagnostic evidence”.

It can be assumed that patients with a high pretest probability of CHD will need invasive coronary angiography and patients with a low pretest probability of CHD will not need subsequent revascularisation. Therefore, CT coronary angiography may be used before performing invasive coronary angiography in patients with an intermediate pretest probability of CHD.

For identifying or excluding of obstructive coronary stenosis, CT coronary angiography was shown to be more cost-saving at a pretest probability of CHD of 50 % or lower, and invasive coronary angiography at a pretest probability of CHD of 70 % or higher. The use of both types of coronary angiography to identify or to exclude functionally relevant coronary stenoses should be regarded as highly cost-consuming.

With regard to ethical, social or legal aspects, the following possible implications were identified: under-provision or over-provision of health care, unnecessary complications, anxiety, social stigmatisation, restriction of self-determination, unequal access to health care, unfair resource distribution and legal disputes.

Conclusion

From a medical point of view, CT coronary angiography using scanners with at least 64 slices should be recommended as a test to rule out obstructive coronary stenoses in order to avoid inappropriate invasive coronary angiography in patients with an intermediate pretest probability of CHD. From a health economic point of view, this recommendation should be limited to patients with a pretest probability of CHD of 50 % or lower.

From a medical and health economic point of view, neither CT coronary angiography using scanners with at least 64 slices nor invasive coronary angiography may be recommended as a single diagnostic test for identifying or ruling out functionally relevant coronary stenoses.

To minimise any potential negative ethical, social and legal implications, the general ethical and moral principles of benefit, autonomy and justice should be considered.

Keywords: CHD, coronary angiography, coronary disease, coronary heart disease, cost-benefit-analysis, diagnosis, EBM, evidence based medicine, evidence-based medicine, health technology assessment, health-economic analysis, HTA, humans, meta-analysis, meta-analysis as topic, review literature as topic, stenosis, systematic review


Summary

Health political and scientific background

Coronary heart disease (CHD) is one of the most common clinical disorders of great epidemiological and economic importance. CHD is associated with symptoms of reduced blood supply to the heart muscle (e. g., angina pectoris) and increased risk of thrombotic events (e. g., myocardial infarction).

Various tests are used in the diagnosis of CHD, including coronary angiography with cardiac catheterisation, also referred to as conventional invasive coronary angiography and coronary angiography without cardiac catheterisation, also referred to as computed tomography (CT) coronary angiography. Since coronary arteries are very small vessels that move rapidly because of heart muscle contractions, CT coronary angiography must fulfil high technical requirements to avoid distorted images.

Due to its ability to assess coronary stenoses and its potential for immediate quality control of the performed revascularisation, invasive coronary angiography is currently regarded as the “gold standard” for diagnosis of stenosis-related CHD. However, a subsequent coronary intervention is performed in only about 40 % of the invasive coronary angiographies. In addition, invasive coronary angiography is associated with the risk of serious complications. Therefore, a non-invasive test capable of reliably verifying or excluding functionally or prognostically relevant coronary stenoses should be able to replace invasive coronary angiography and, probably, other diagnostic tests.

Especially due to its lower risk of complications and higher potential for prediction of severe cardiovascular events (owing to the assessment of not-calcified vulnerable plaques prone to rupture), CT coronary angiography could play an increasing role in the diagnosis of CHD and treatment decision-making. Currently, CT coronary angiography is primarily being discussed as a test to exclude obstructive (over 50 %) coronary artery stenoses and, therefore, to avoid invasive coronary angiography in a large number of patients.

However, both diagnostic tests provide only limited information about the functional relevance of the identified stenoses and about their predictive value for future coronary events. Therefore, the value of both types of coronary angiographies for CHD diagnosis as well as for revascularisation decision-making has been challenged.

The present report aims to compare the effectiveness, side effects, radiation dose, diagnostic and prognostic value, costs and cost-effectiveness of conventional invasive coronary angiography versus CT coronary angiography as well as to identify ethical, social and legal implications based on a systematic review of the literature.

Research questions

Medical evaluation

What are the clinical efficacy, diagnostic accuracy and prognostic value of CT coronary angiography compared to that of conventional invasive coronary angiography in the diagnosis of CHD?

Health economic evaluation

What are the costs of CT coronary angiography compared to that of conventional invasive coronary angiography in relation to clinical efficacy, diagnostic accuracy or prognostic value in the diagnosis of CHD?

Ethical, social and legal evaluation

Which ethical, social and legal implications should be considered in the use of CT coronary angiography or conventional invasive coronary angiography in the diagnosis of CHD?

Methods

Medical evaluation

The literature search was conducted in medical electronic databases (MEDLINE, EMBASE etc.) in October 2010 and was completed with a manual search. The search was restricted to articles published from 2006 in German or English. Two independent reviewers were involved in the selection of the relevant publications.

Primarily, systematic reviews of controlled clinical, diagnostic or prognostic studies comparing CT coronary angiography with invasive coronary angiography in the diagnosis of CHD were selected from the identified hits. The addressed endpoints were mortality, morbidity as well as parameters of diagnostic and prognostic value.

Secondly, the identified hits were screened to identify controlled clinical studies and prognostic studies comparing CT coronary angiography and invasive coronary angiography in the diagnosis of CHD. Additionally, hits were screened for diagnostic studies using intracoronary pressure measurement or intravascular ultrasound as the reference standard.

Systematic reviews and studies on special indications (bypass or in-stent-restenosis) as well as abstracts and segment-based analyses were not included in the evaluation. Only data obtained using CT scanners with at least 64 slices were considered for inclusion. Additionally, data on radiation doses from current non-systematic reviews were also taken into account.

The selected systematic reviews were evaluated for risk of bias. The pool of the included diagnostic studies was checked, and the quality of the studies was assessed using information in the systematic reviews. Using data from studies presented in these reviews, a meta-analysis was conducted only for data obtained using 64-slice CT scanners.

The meta-analysis was performed to determine the sensitivity, specificity, positive likelihood ratio (LR+) and negative likelihood ratio (LR-) by calculating the 95 % confidence interval (CI) in the random effects model using the Meta-DiSc programme. The area under the curve (AUC) of the receiver operating characteristic curve (ROC) was also assessed. Due to the heterogeneity of the study results, a meta-analysis was also conducted for studies of higher methodological quality.

The identified diagnostic studies using intracoronary pressure measurement as the reference standard were also evaluated methodologically. The synthesis of the information from these studies was performed qualitatively.

Additionally, the proportions of patients with true positive or true negative diagnoses as well as the effective radiation doses were calculated as a function of pretest probability for different scenarios of CT coronary angiography or of invasive coronary angiography, using in each scenario invasive coronary angiography or intracoronary pressure measurement as the reference standard.

Health economic evaluation

The literature search was conducted in health economic relevant medical electronic databases in October 2010. The search was restricted to articles published from 2006 in German or English. Two independent reviewers were involved in the selection of the relevant publications.

Systematic reviews of studies with health economic analyses, health economic studies or models comparing CT angiography with invasive coronary angiography in the diagnosis of CHD for the German health system based on assumptions from systematic reviews were selected from the identified hits. The addressed endpoints were costs and cost-effectiveness.

Health economic evaluations on special indications (bypass or in-stent-restenosis), abstracts and segment-based analyses were not included in the evaluation. Only data obtained using CT scanners with at least 64 slices were considered for inclusion. The objectives, methods, results and conclusions of the identified health economic studies were described.

Health economic modelling was performed to estimate the total cost per patient and the cost per patient with true positive diagnosis for CT coronary angiography and invasive coronary angiography as a function of pretest probability for different scenarios, using invasive coronary angiography or intracoronary pressure measurement as the reference standard.

The clinical assumptions used in modelling were predominantly derived from the medical evaluation (e. g., for sensitivity, specificity). The costs were observed from the social perspective and were derived from contemporary German sources.

Ethical, social and legal evaluation

The conducted literature search also aimed to identify publications dealing explicitly with ethical, social or legal aspects of using CT coronary angiography and invasive coronary angiography in CHD diagnosis. Identified publications were described. Synthesis of information was performed qualitatively.

Results

Medical evaluation
Results of the literature search

The systematic literature search yielded 1,913 hits. Overall, 15 systematic reviews and two diagnostic studies were included in the medical evaluation.

Clinical efficacy and prognostic value

No studies were found on the clinical efficacy or prognostic value of CT coronary angiography in comparison to conventional invasive coronary angiography in the diagnosis of CHD.

Diagnostic accuracy using invasive coronary angiography as the reference standard

To assess the diagnostic accuracy of CT coronary angiography using invasive coronary angiography as the reference standard (identification of obstructive coronary stenoses), 15 systematic reviews with data from 44 studies obtained using at least 64 slices CT scanners were evaluated. Meta-analysis of the nine studies of higher methodological quality showed that CT coronary angiography had a sensitivity of 96 % (95 % CI: 93 % to 98 %), specificity of 86 % (95 % CI: 83 % to 89 %), LR+ of 6.38 (95 % CI: 5.18 to 7.87) and LR- of 0.06 (95 % CI: 0.03 to 0.10). The AUC of the ROC curve was 0.962 ± 0.023 and the Q* value 0.91 ± 0.03 (average ± standard error). However, due to non-diagnostic CT images approximately 3.6 % of the examined patients required a subsequent invasive coronary angiography.

Diagnostic accuracy using intracoronary pressure measurement as the reference standard

Regarding the comparison of CT coronary angiography and invasive coronary angiography using intracoronary pressure measurement as the reference standard (identification of functionally relevant coronary stenoses), two studies were identified and data from one study were found to be applicable. Sensitivity was 80 % (95 % CI: 61 % to 92 %) versus 67 % (95 % CI: 51 % to 78 %), specificity 67 % (95 % CI: 47 % to 83 %) versus 75 % (95 % CI: 60 % to 86 %), average LR+ 2.3 versus 2.6, and average LR- 0.3 versus 0.4, respectively.

Comparison of diagnostic accuracy using invasive coronary angiography as the reference standard versus intracoronary pressure measurement as the reference standard

Due to lower sensitivity and lower specifity of both types of coronary angiography using intracoronary pressure measurement as the reference standard compared to invasive coronary angiography as the reference standard, the proportions of patients with true positive and/or true negative diagnoses were lower. Generally, less than 80 % of patients were classified correctly by CT coronary angiography as well as invasive coronary angiography using intracoronary pressure measurement as the reference standard. This proportion was definitely lower compared to that using invasive coronary angiography as the reference standard.

Contrast medium dose and radiation dose

No comparative meta-analysis of CT coronary angiography and invasive coronary angiography was found regarding contrast medium dose and effective radiation dose. The average contrast medium dose calculated from 43 studies using CT scanners with more than 16 slices was 31.3 g, the average effective radiation dose calculated from 29 studies using CT scanners with more than 16 slices and retrospective electrocardiogram (ECG) gating was 13.0 mSv.

The effective radiation doses of invasive coronary angiography and of CT coronary angiography with prospective ECG gating (approximately 5 to 7 mSv and 2 to 4 mSv, respectively; data derived from non-systematic reviews) were on average lower than those of CT coronary angiography with retrospective ECG gating. Considering the strategy of CT coronary angiography with subsequent invasive coronary angiography in case of positive findings, the average effective dose rose with increasing pretest probability of CHD. Compared to invasive coronary angiography, the average effective radiation dose of CT coronary angiography with prospective ECG gating was relatively similar.

Health economic evaluation
Results of the literature search

The systematic literature search yielded 97 hits. After screening the full texts, only one publication was included in the health economic evaluation.

Appraisal of the included study

At a pretest probability of CHD of 50 % or lower, the study revealed that CT coronary angiography was associated with lower cost per correctly diagnosed patient with obstructive coronary stenosis. At a pretest probability of 70 % or higher, invasive coronary angiography resulted in lower cost per correctly diagnosed patient with obstructive coronary stenosis.

Results of health economic modelling

Comparison of CT coronary angiography with invasive coronary angiography using invasive coronary angiography as the reference standard revealed that the total cost per patient diagnosed using CT coronary angiography increases as a function of pretest probability of CHD. The curves for total cost per patient for both diagnostic tests intersected at an approximately 60 % pretest probability of CHD. At a pretest probability of CHD of 50 % or lower, CT coronary angiography resulted in lower cost per patient with true positive diagnosis. At a pretest probability of CHD of 70 % or higher, invasive coronary angiography was associated with lower cost per patient with true positive diagnosis.

Use of intracoronary pressure measurement as the reference standard affected the results considerably compared to those using invasive coronary angiography as the reference standard. Both types of coronary angiographies showed a substantial increase in total cost per patient and in total cost per patient with true positive diagnosis, particularly at a low pretest probability of CHD.

Ethical, social and legal evaluation

Two publications were identified. The first publication dealt with ethical considerations in the use of CT coronary angiography. The ethical aspects were discussed within the scope of the three ethical principles beneficence, autonomy and justice. The second publication addressed primarily the ethical implications of CT coronary angiography with regard to radiation exposure, particularly when used within studies.

Discussion

Medical evaluation
Methodological aspects

Various methodological aspects relating to the literature search, the identified systematic reviews, the diagnostic studies and the performed synthesis of information can bias the results of medical evaluation. The validity of the conducted meta-analyses depends on the validity of each diagnostic study and the validity of the combined results derived from studies with somewhat different populations and technology modifications.

Invasive coronary angiography is a reliable reference standard for the identification of coronary stenoses, whereas intracoronary pressure measurement for the detection of functionally relevant stenoses. However, both tests are not convincing with regard to prognostic value.

Interpretation of the results

The clinical efficacy and prognostic value of CT coronary angiography versus invasive coronary angiography in the diagnosis of CHD cannot be estimated based on the current data since the corresponding studies are lacking.

The discriminatory power of CT coronary angiography to identify patients with obstructive coronary stenoses (according to LR+) should be regarded as “high diagnostic evidence”, and its power to identify patients without obstructive coronary stenoses (according to LR-) as “excellent diagnostic evidence”. Therefore, CT coronary angiography using scanners with at least 64 slices should be considered as a test for the exclusion of obstructive coronary stenoses.

However, it can be assumed that patients with a high pretest probability of CHD will need invasive coronary angiography and patients with a low pretest probability will not need subsequent revascularisation. Therefore, CT coronary angiography may be used before performing invasive coronary angiography in patients with an intermediate pretest probability of CHD.

For identifying patients with or without functionally relevant stenoses, the discriminatory power of CT coronary angiography and of invasive coronary angiography should be regarded only as “weak diagnostic evidence”. As only two small and not methodologically flawless studies were available, their results should be regarded with great caution. Nevertheless, these data should be seen as a warning against the excessive use of coronary angiography without reliable blood flow assessment.

The obtained results reflect the rapid development of CT coronary angiography with regard to the reduction of radiation dose. The effective radiation dose of CT coronary angiography with prospective ECG gating is similar to that of invasive coronary angiography.

Health economic evaluation
Methodological aspects

Various methodological aspects relating to the literature search and the modelling methods can bias the results of health economic modelling.

The use of clinical assumptions from a contemporary meta-analysis and cost assumptions for the German health system enables a high level of evidence of the health economic modelling and to avoid problems of transferability of the results.

Interpretation of the results

The cost per avoided cardiovascular event or per quality-adjusted life-year gained of CT coronary angiography in comparison to invasive coronary angiography in the diagnosis of CHD cannot be determined based on the current data since the corresponding studies are lacking.

For identifying or excluding obstructive coronary stenosis, CT coronary angiography was shown to be more cost-saving at a pretest probability of CHD of 50 % or lower, and invasive coronary angiography at a pretest probability of CHD of 70 % or higher.

The use of each type of coronary angiography to identify or to exclude functionally relevant coronary stenoses should be regarded as highly cost-consuming. However, parameters of diagnostic accuracy were derived from a single small study, limiting the conclusiveness of the analysis.

Ethical, social and legal evaluation

With regard to ethical, social or legal aspects, the following possible implications were derived from the analysed publications: under-provision or over-provision of health care, unnecessary complications, anxiety, social stigmatisation, restriction of self-determination, unequal access to health care, unfair resource distribution and legal disputes.

No data were found in the publications concerning differences between CT coronary angiography and invasive coronary angiography with regard to ethical, social or legal implications not related to differences in diagnostic accuracy.

Conclusions

From a medical point of view, CT coronary angiography using scanners with at least 64 slices should be recommended as a test to rule out obstructive coronary stenoses in order to avoid inappropriate invasive coronary angiography in patients with an intermediate pretest probability of CHD. From a health economic point of view, this recommendation should be limited to patients with a pretest probability of CHD of 50 % or lower.

From a medical and health economic point of view, neither CT coronary angiography using scanners with at least 64 slices nor invasive coronary angiography may be recommended as a single diagnostic test for identifying or ruling out functionally relevant coronary stenoses.

To minimise any potential negative ethical, social and legal implications, the general ethical-moral principles of benefit, autonomy and justice should be considered.