[PDF](+69👁️) Télécharger CT coronary angiography vs. invasive coronary angiography in CHD. pdf

OPEN ACCESS



This is the original (English) version.
The translated (German) version starts at p. 9.



HTA Summary



CT coronary angiography vs. invasive coronary angiography
in CHD



Abstract



Scientific background

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

Research questions

The present report aims to evaluate the clinical efficacy, diagnostic ac-
curacy, 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.



Vitali Gorenoi 1
Matthias P.
Schonermark 1
Anja Hagen 1



1 Institute for Epidemiology,
Social Medicine and Health
Systems Research,
Hannover, Germany



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 in-
volved 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 radi-
ation doses from current non-systematic reviews were taken into ac-
count.

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 in-
cluded in the evaluation. Only data obtained using CT scanners with at
least 64 slices were considered.



Results



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

Overall, 15 systematic reviews with data from 44 diagnostic studies
using invasive coronary angiography as the reference standard (identi-
fication of obstructive stenoses) and two diagnostic studies using in-
tracoronary pressure measurement as the reference standard (identi-
fication 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 an-
giography 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



errs



medizinwissen



GMS Health Technology Assessment 2012, Vol. 8, ISSN 1861-8863



1/16



Gorenoi et al.: CT coronary angiography vs. invasive coronary angiography ...



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 radi-
ation 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 an-
giographies 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 benefi-
cence, 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, restric-
tion 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



CITS



medizinwissen



GMS Health Technology Assessment 2012, Vol. 8, ISSN 1861-8863



2/16



Gorenoi et al.: CT coronary angiography vs. invasive coronary angiography ...



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



errs



medizinwissen



GMS Health Technology Assessment 2012, Vol. 8, ISSN 1861-8863



3/16



Gorenoi et al.: CT coronary angiography vs. invasive coronary angiography ...



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 ves-
sels that move rapidly because of heart muscle contrac-
tions, CT coronary angiography must fulfil high technical
requirements to avoid distorted images.
Due to its ability to assess coronary stenoses and its po-
tential for immediate quality control of the performed re-
vascularisation, invasive coronary angiography is currently
regarded as the "gold standard" for diagnosis of stenosis-
related CHD. However, a subsequent coronary interven-
tion is performed in only about 40 % of the invasive
coronary angiographies. In addition, invasive coronary
angiography is associated with the risk of serious compli-
cations. Therefore, a non-invasive test capable of reliably
verifying or excluding functionally or prognostically rele-
vant 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 vulner-
able plaques prone to rupture), CT coronary angiography
could play an increasing role in the diagnosis of CHD and
treatment decision-making. Currently, CT coronary an-
giography 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 infor-
mation 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 inva-
sive 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 prog-
nostic 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 diag-
nosis 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, diag-
nostic or prognostic studies comparing CT coronary an-
giography 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 compar-
ing CT coronary angiography and invasive coronary an-
giography 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 evalu-
ation. 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



CITS



medmnwiiien



GMS Health Technology Assessment 2012, Vol. 8, ISSN 1861-8863



4/16



Gorenoi et al.: CT coronary angiography vs. invasive coronary angiography ...



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 in-
formation from these studies was performed qualitatively.
Additionally, the proportions of patients with true positive
or true negative diagnoses as well as the effective radi-
ation doses were calculated as a function of pretest
probability for different scenarios of CT coronary an-
giography or of invasive coronary angiography, using in
each scenario invasive coronary angiography or intracoron-
ary 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 (by-
pass 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 modellingwere predom-
inantly 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 publi-
cations 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 prognos-
tic value of CT coronary angiography in comparison to
conventional invasive coronary angiography in the diag-
nosis of CHD.

Diagnostic accuracy using invasive coronary angiography
as the reference standard

To assess the diagnostic accuracy of CT coronary an-
giography 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 ap-
proximately 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 (iden-
tification 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.



CITS



medizinwissen



GMS Health Technology Assessment 2012, Vol. 8, ISSN 1861-8863



5/16



Gorenoi et al.: CT coronary angiography vs. invasive coronary angiography ...



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 an-
giography 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 refer-
ence 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 an-
giography and of CT coronary angiography with prospect-
ive 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 an-
giography with retrospective ECG gating. Considering the
strategy of CT coronary angiography with subsequent in-
vasive coronary angiography in case of positive findings,
the average effective dose rose with increasing pretest
probability of CHD. Compared to invasive coronary an-
giography, 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
screeningthe 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 ob-
structive coronary stenosis. At a pretest probability of
70 % or higher, invasive coronary angiography resulted



in lower cost per correctly diagnosed patient with obstruct-
ive 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 in-
creases 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 refer-
ence standard affected the results considerably compared
to those using invasive coronary angiography as the ref-
erence 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,
autonomyandjustice.Thesecond publication addressed
primarily the ethical implications of CT coronary an-
giography 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.



CITS



medizinwissen



GMS Health Technology Assessment 2012, Vol. 8, ISSN 1861-8863



6/16



Gorenoi et al.: CT coronary angiography vs. invasive coronary angiography ...



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 (ac-
cording to LR+) should be regarded as "high diagnostic
evidence", and its power to identify patients without ob-
structive coronary stenoses (according to LR-) as "excel-
lent diagnostic evidence". Therefore, CT coronary an-
giography 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 inter-
mediate pretest probability of CHD.
For identifying patients with or without functionally rele-
vant 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 an-
giography without reliable blood flow assessment.
The obtained results reflect the rapid development of CT
coronary angiography with regard to the reduction of ra-
diation 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 follow-
ing possible implications were derived from the analysed
publications: under-provision or over-provision of health
care, unnecessary complications, anxiety, social stigma-
tisation, restriction of self-determination, unequal access
to health care, unfair resource distribution and legal dis-
putes.

No data were found in the publications concerning differ-
ences 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 recom-
mended as a test to rule out obstructive coronary sten-
oses 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.



Corresponding author:

Dr. med. Vitali Gorenoi, MPH

Institute for Epidemiology, Social Medicine and Health
Systems Research, Hannover Medical School,
Carl-Neuberg-Str. 1, 30625 Hannover, Germany, Phone:
+49 (0)511/532-9345
gorenoi.vitali@mh-hannover.de

Please cite as

Gorenoi V, Schonermark MP, Hagen A. CT coronary angiography vs.
invasive coronary angiography in CHD. GMS Health Technol Assess.
2012;8:Doc02.

DOI: 10.3205/htaOOOlOO, URN: urn:nbn:de:0183-hta0001009



CITS



medizinwissen



GMS Health Technology Assessment 2012, Vol. 8, ISSN 1861-8863



7/16



Gorenoi et al.: CT coronary angiography vs. invasive coronary angiography ...



This article is freely available from

http://www.egms.de/en/journals/hta/2012-8/hta000100.shtml
Published: 2012-04-16

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



Copyright

©2012 Gorenoi et al. This is an Open Access article distributed under
the terms of the Creative Commons Attribution License
(http://creativecommons.Org/iicenses/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.



errs



medizinwissen



GMS Health Technology Assessment 2012, Vol. 8, ISSN 1861-8863



8/16



OPEN ACCESS



This is the translated (German) version.
The original (English) version starts at p. 1.



HTA-Kurzfassung



CT-Koronarangiografie versus konventionelle invasive
Koronarangiografie bei der KHK-Diagnostik

Zusammenfassung
Wissenschaftlicher Hintergrund

Zur Diagnose der koronaren Herzkrankheit(KHK) werden verschiedene
Verfahren eingesetzt, darunter die konventionelle invasive Koronaran-
giografie und die nicht invasive computertomografische (CT) Koronaran-
giografie.

Fragestellung

Es stellen sich Fragen nach der klinischen Wirksamkeit, der diagnosti-
schen Genauigkeit, der prognostischen Gute, der Kosten-Wirksamkeit
sowie nach ethischen, sozialen und juristischen Implikationen der
CT-Koronarangiografie vs. invasive Koronarangiografie bei der KHK-
Diagnostik.

Methodik

Einesystematische Literaturrecherche wird im 0ktober2010 in elektro-
nischen Datenbanken (MEDLINE, EMBASE etc.) durchgefuhrt und durch
eine Handsuche erganzt. Die Literaturrecherche wird auf Publikationen
ab 2006 sowie auf die Sprachen Deutsch oder Englisch eingeschrankt.
Zwei unabhangige Reviewer sind an der Selektion der relevanten Publi-
kationen beteiligt.

Bei der medizinischen Bewertung werden diesystematischen Ubersich-
ten diagnostischer Studien mit dem Referenzstandard invasive Koro-
narangiografie sowie diagnostischeStudien mitdem Referenzstandard
intrakoronare Druckmessung ausgewertet. Studienergebnisse werden
mittels einer Metaanalyse auf dem 95 %-Konfidenzintervall (CI) zusam-
mengefasst. Zusatzlich werden Daten zur Strahlendosis aus aktuellen
nicht systematischen Ubersichten berucksichtigt.
Bei der gesundheitsdkonomischen Bewertung wird eine Modellierung
aus gesellschaftlicher Perspektive mit klinischen Annahmen aus der
Metaanalyse und okonomischen Annahmen aus aktuellen deutschen
Quellen durchgefuhrt.

Informationsquellen zu speziellen Fragestellungen (Bypass- bzw. In-
Stent-Restenosen) werden nicht berucksichtigt. Es werden ausschlieBlich
Daten zu mindestens 64-Zeilen-CT-Geraten betrachtet.

Ergebnisse

Es liegen keine Studien zur medizinischen Wirksamkeit und zur pro-
gnostischen Gute von CT-Koronarangiografie vs. konventionelle invasive
Koronarangiografie bei der Diagnostik der KHK vor.
Es werden 15 systematische Ubersichten mit Daten aus 44 diagnosti-
schen Studien bezogen auf den Referenzstandard invasive Koronaran-
giografie (Identifikation obstruktiverStenosen) und zwei diagnostische
Studien bezogen auf den Referenzstandard intrakoronare Druckmessung
(Identifikation funktionell relevanterStenosen) in die medizinische Be-
wertung einbezogen.

Die durch die eigene Metaanalyse der neun methodisch besseren Stu-
dien ermittelte Sensitivitat fur die CT-Koronarangiografie bezogen auf



Vitali Gorenoi 1
Matthias P.
Schonermark 1
Anja Hagen 1

1 Abteilungfur Epidemiologie,
Sozialmedizin und
Gesu nd heitssystemforsch u ng,
Hannover, Deutschland



CITS



medizinwissen



GMS Health Technology Assessment 2012, Vol. 8, ISSN 1861-8863



9/16



Gorenoi et al.: CT-Koronarangiografie versus konventionelle invasive ...



den Referenzstandard invasive Koronarangiografie betragt 96 %
(95 % CI: 93 % bis 98 %), die Spezifitat 86 % (95 % CI: 83 % bis 89 %),
die positive Likelihood-Ratio 6,38 (95 % CI: 5,18 bis 7,87) und die ne-
gative Likelihood-Ratio 0,06 (95 % CI: 0,03 bis 0,10). Aufgrund nicht
auswertbarer CT-Koronarangiografien werden circa 3,6 % der untersuch-
ten Patienten trotzdem noch mittels einer invasiven Koronarangiografie
untersucht.

Die Sensitivitat der CT-Koronarangiografie vs. invasive Koronarangiogra-
fie bezogen auf den Referenzstandard intrakoronare Druckmessung
betragt entsprechend 80 % (95 % CI: 61 % bis 92 %) vs. 67 % (95 % CI:
51 % bis 78 %), die Spezifitat 67 % (95 % CI: 47 % bis 83 %) vs. 75 %
(95 % CI: 60 % bis 86 %), die durchschnittliche positive Likelihood-Ratio
2,3 vs. 2,6 und die durchschnittliche negative Likelihood-Ratio
0,3 vs. 0,4.

Verglichen mit invasiver Koronarangiografie ist die durchschnittliche
effektive Strahlendosis bei der CT-Koronarangiografie mit retrospektivem
Elektrokardiogramm (EKG)-Gating hoher und mit prospektivem EKG-
Gating relativ ahnlich.

Im Rahmen der gesundheitsokonomischen Modellierung bezogen auf
den Referenzstandard invasive Koronarangiografie sind bei einer Pra-
testwahrscheinlichkeit fur KHK bis 50 % die Kosten der CT-Koronaran-
giografie und ab 70 % die der invasiven Koronarangiografie niedriger
pro richtig positiv diagnostiziertem Patienten. Bezogen auf den Refe-
renzstandard intrakoronare Druckmessung sind erheblich hohere
Kosten pro richtig positiv diagnostiziertem Patienten fur die beiden
Koronarangiografietypen zu verzeichnen.

Es werden zwei Publikationen zu ethischen Aspekten identifiziert: in
der ersten werden die ethischen Gesichtspunkte in Bezug auf die Prin-
zipien Wohltat, Autonomie und Gerechtigkeit betrachtet, in der zweiten
in Bezug auf die Bestrahlungsexposition, insbesondere bei der Anwen-
dung innerhalb von Studien.

Diskussion

Die Trennscharfe der CT-Koronarangiografie zur Identifikation von Pati-
enten mit obstruktiven (uber 50%igen) Koronarstenosen ist als „hohe
diagnostische Evidenz", zur Identifikation von Patienten ohne obstruk-
tive Koronarstenosen als „uberzeugende diagnostische Evidenz" zu
betrachten. Zur Identifikation von Patienten mit bzw. ohne funktionell
relevante Koronarstenosen ist die Trennscharfe der beiden Koronaran-
giografietypen als „schwache diagnostische Evidenz" einzuschatzen.
Bei Patienten mit hoher Pratestwahrscheinlichkeit fur KHK ist von der
notwendigen Durchfuhrung einer invasiven Koronarangiografie und bei
Patienten mit niedriger von einemfehlenden Bedarf an anschlieSender
Revaskularisation auszugehen. Die CT-Koronarangiografie ware somit
als Vorschalttest vor invasiver Koronarangiografie bei Patienten mit
mittlerer Pratestwahrscheinlichkeit fur KHK anwendbar.
Zur Identifikation bzw. zum Ausschluss von obstruktiven Koronarsteno-
sen zeigtsich, dass bei der Pratestwahrscheinlichkeit fur KHK bis 50 %
die CT-Koronarangiografie und ab 70 % die invasive Koronarangiografie
kostengunstigerer ist. Es ist von einem ubermaSigen Kostenverbrauch
beim Einsatz der jeweiligen Koronarangiografietypen zur Identifikation
bzw. zum Ausschluss der funktionell relevanten Koronarstenosen aus-
zugehen.

In Bezug auf ethische, soziale oder juristische Aspekte lassen sich fol-
gende mogliche Implikationen ableiten: Unter- bzw. Uberversorgung mit
Gesundheitsleistungen, unnotige Komplikationen, Verangstigung und
Stigmatisierung der Patienten, Einschrankung der Selbstbestimmung,



CITS



mMizinwi^en



GMS Health Technology Assessment 2012, Vol. 8, ISSN 1861-8863



10/16



Gorenoi et al.: CT-Koronarangiografie versus konventionelle invasive ...



ungleicherZugangzur medizinischen Versorgung, ungerechte Ressour-
cenverteilung sowie juristische Auseinandersetzungen.

Schlussfolgerungen

Zum Ausschluss obstruktiver Koronarstenosen ist die CT-Koronarangio-
grafie mit mindestens 64-zeiligen Geraten als Vorschaltetest zur Ver-
meidung einer unangemessenen invasiven Koronarangiografie aus
medizinischer Sicht bei Patienten mit mittlerer Pratestwahrscheinlichkeit
fur KHK, dabei aus gesundheitsokonomischer Sicht bei Patienten bis
einschlieSlich 50%iger Pratestwahrscheinlichkeit fur KHK, zu empfehlen.
Zur Identifikation bzw. zum Ausschluss funktionell relevanter Koronar-
stenosen konnen sowohl aus medizinischer als auch aus gesundheits-
okonomischer Sicht weder die CT-Koronarangiografie mit mindestens
64-zeiligen Geraten noch die invasive Koronarangiografie als alleiniges
diagnostisches Verfahren empfohlen werden.
Urn potenzielle negative ethische, soziale und juristische Implikationen
zu minimieren, sollen die ethisch-moralischen Prinzipien Wohltat, Auto-
nomic und Gerechtigkeit beachtet werden.

Schliisselworter: Diagnose, Diagnostik, EBM, evidenzbasierte Medizin,
gesundheitsdkonomische Analyse, gutachtenbasierte Medizin, Health
Technology Assessment, HTA, KHK, Koronarangiographie, koronare
Erkrankung, koronare Herzkrankheit, Koronarkrankheit,
Kosten-Nutzen-Analyse, Mensch, Metaanalyse, M eta-Analyse, Stenose,
systematisches Review, systematische Ubersicht, Ubersichtsliteratur



errs



medizinwissen



GMS Health Technology Assessment 2012, Vol. 8, ISSN 1861-8863



11/16



Gorenoi et al.: CT-Koronarangiografie versus konventionelle invasive ...



Kurzfassung

Gesundheitspolitischer und
wissenschaftlicher Hintergrund

Die koronare Herzkrankheit(KHK) gehortzu den haufigs-
ten Krankheitsbildern mit groSer epidemiologischer und
volkswirtschaftlicher Bedeutung. Eine KHK ist mit Sym-
ptomen der verringerten Versorgung des Herzmuskels
(z. B. Angina Pectoris) und miteinem erhohten Risiko fur
thrombotische Ereignisse (z. B. Myokardinfarkt) verbun-
den.

Zur Diagnose der KHK werden verschiedene Verfahren
eingesetzt, darunter die Koronarangiografie mit Herzka-
thetereinsatz, sogenannte konventionelle invasive Koro-
narangiografie, und zunehmend die Koronarangiografie
ohne Herzkathetereinsatz, sogenannte computertomogra-
fische (CT) Koronarangiografie. Da die Koronararterien
sehr klein sind, die durch das Zusammenziehen des
Herzmuskels sehr schnell bewegt werden, muss die CT-
Koronarangiografie hohe technische Voraussetzungen
zur Vermeidung einer fehlerhaften Bilddarstellung erful-
len.

Die invasive Koronarangiografie gilt bislang durch die
Beurteilbarkeit von Koronarstenosen und durch die
Moglichkeit zur unmittelbareren Erfolgskontrolle der
durchgefuhrten Revaskularisation als Goldstandard fur
die Diagnostik einer durch eine Stenose verursachten
KHK. Es erfolgt allerdings nur bei etwa 40 % der invasiven
Koronarangiografien eine direkt anschlieSende Koronar-
intervention. Die invasive Koronarangiografie istzusatzlich
mit dem Risiko ernsthafter Komplikationen verbunden.
Somit konnte ein nicht-invasives Verfahren, das die fur
die Durchblutung und die Prognose relevanten Koronar-
stenosen sicher nachweist bzw. ausschlieSt, die invasive
Koronarangiografie und ggf. andere Diagnostik ersetzen.
Insbesondere wegen des geringeren Komplikationsrisikos
und des hoheren Potenzials hinsichtlich der Prognose
schwerer kardiovaskularer Ereignisse (durch die Beurtei-
lungvon nicht-kalzifizierten rupturgefahrdeten Plaques),
wird der CT-Koronarangiografie eine zunehmend groBere
Rolle im Rahmen der KHK-Diagnostik und derTherapie-
auswahl zugeschrieben. Aktuell wird die CT-Koronarangio-
grafie primar als Verfahren diskutiert, urn das Vorliegen
von obstruktiven (Gber50%igen) Koronararterienstenosen
bei Patienten auszuschlieSen und somit bei einer groSe-
ren Anzahl an Patienten auf eine invasive Koronarangio-
grafie verzichten zu konnen.

Die beiden diagnostischen Untersuchungen liefern aller-
dings nur eingeschrankte Informationen uber die Rele-
vanz der identifizierten Stenose fur die Durchblutungssto-
rung und fur die Prognose hinsichtlich zukunftiger koro-
narer Ereignisse. Somit wird der Stellenwert der Koro-
narangiografien fur die KHK-Diagnostik und fur die Ent-
scheidungfur odergegen eine Revaskularisation insge-
samt infrage gestellt.

Der Vergleich von Wirksamkeit, Nebenwirkungen, Strah-
lendosis, diagnostischer und prognostischer Gute, Kosten



und Kosten-Wirksamkeit von konventioneller invasiver
Koronarangiografie vs. CT-Koronarangiografie sowie das
Auffinden von ethischen, sozialen und juristischen Impli-
kationen auf Basis einer systematischen Literaturuber-
sicht sind Ziele des vorliegenden Berichts.

Fragestellung
Medizinische Bewertung

Wie ist die medizinische Wirksamkeit, die diagnostische
Genauigkeit sowie die prognostische Gute der CT-Koro-
narangiografie im Vergleich zu konventioneller invasiver
Koronarangiografie bei der Diagnostik der KHK?

Gesundheitsokonomische Bewertung

Wie sind die Kosten der CT-Koronarangiografie im Ver-
gleich zu denen konventioneller invasiver Koronarangio-
grafie in Relation zu medizinischer Wirksamkeit, dia-
gnostischer Genauigkeit oder prognostischer Gute bei
der Diagnostik der KHK?

Ethische, soziale und juristische Bewertung

Welche ethischen, sozialen und juristischen Implikationen
sind beim Einsatz der CT-Koronarangiografie oder der
konventionellen invasiven Koronarangiografie bei der
Diagnostik der KHK zu beachten?

Methodik

Medizinische Bewertung

Die Literaturrecherche wird in medizinischen elektroni-
schen Datenbanken (MEDLINE, EMBASE etc.) im Oktober
2010 durchgefuhrt und durch eine Handsuche erganzt.
Die Recherche wird auf Publikationensdatum ab 2006
eingeschrankt sowie auf die Sprachen Deutsch oder
Englisch begrenzt. Zwei unabhangige Reviewer sind an
derSelektion der relevanten Publikationen beteiligt.
Zunachst werden aus den identifizierten Treffern syste-
matische Ubersichten von kontrollierten klinischen, dia-
gnostischen bzw. prognostischen Studien zum Vergleich
CT-Koronarangiografie vs. invasive Koronarangiografie
bei der KHK-Diagnostik ausgewah It. AlseinzuschlieSende
Endpunktegelten Mortalitat, Morbiditat sowie Parameter
der diagnostischen und der prognostischen Gute.
AnschlieSend wird in den identifizierten Treffern nach
kontrollierten klinischen Studien und prognostischen
Studien zum Vergleich von CT-Koronarangiografie vs. in-
vasive Koronarangiografie bei der KHK-Diagnostik und
zusatzlich nach diagnostischen Studien zu dieser Frage-
stellung mit dem Referenzstandard intrakoronare
Druckmessungoder intravaskularer Ultraschall gesucht.
Systematische Ubersichten und Studien zu speziellen
Fragestellungen (Bypass- bzw. In-Stent-Restenosen), Ab-
stracts sowie Auswertungen auf Segmentbasis werden
nicht berucksichtigt. Es werden ausschlieSlich Informati-



CITS



medizinwissen



GMS Health Technology Assessment 2012, Vol. 8, ISSN 1861-8863



12/16



Gorenoi et al.: CT-Koronarangiografie versus konventionelle invasive ...



onsquellen mit Daten zu mindestens 64-zeiligen CT-Gera-
ten einbezogen. Zusatzlich werden aktuelle Literaturdaten
zur Strahlendosis aus nicht systematischen Ubersichten
berucksichtigt.

Die selektierten systematischen Ubersichten werden einer
Bewertung des Verzerrungspotenzials unterzogen. Der
Pool einbezogenerdiagnostischerStudien wird uberpruft,
die Studienqualitat wird anhand der Angaben in den
systematischen Ubersichten bewertet. Auf Basis der
Studiendaten in diesen Ubersichten wird eine Metaana-
lyse ausschlieSlich fur 64-zeilige Gerate durchgefuhrt.
Bei der Metaanalyse werden die Sensitivitat, Spezifitat,
positive Likelihood-Ratio (LR+) und negative Likelihood-
Ratio (LR-) auf dem 95%igen Konfidenzintervall (CI) im
Random-effect-Modell sowie die area under the curve
(AUC) der receiver operating characteristic (ROC)-Kurve
mithilfe des Programms Meta-DiSc errechnet. Aufgrund
der Heterogenitat der Ergebnisse wird anschlieSend eine
Metaanalyse methodisch bessererStudien durchgefuhrt.
Die identifizierten diagnostischen Studien mit dem Refe-
renzstandard intrakoronare Druckmessung werden
ebenfalls methodisch bewertet. Die Informationssynthese
dieser Studien erfolgt qualitativ.
AuSerdem werden die Patientenanteile mit richtig positi-
ves mit richtig negativen Diagnosen sowie die effektive
Strahlendosis fur verschiedene Szenarien mit Einsatz der
CT-Koronarangiografie Oder der invasiven Koronarangio-
grafie, jeweils mitinvasiver Koronarangiografie bzw. intra-
koronarer Druckmessung als Referenzstandard, in Abhan-
gigkeit von der Pratestwahrscheinlichkeit errechnet.

Gesundheitsokonomische Bewertung

Die Literaturrecherche wird in medizinischen, darunter
auch gesundheitsdkonomisch relevanten, elektronischen
Datenbanken im Oktober 2010 durchgefuhrt. Die Recher-
che wird auf die Publikationsjahreab 2006 sowie auf die
Sprachen Deutsch und Englisch beschrankt. Zwei unab-
hangige Reviewer sind an der Selektion der relevanten
Publikationen beteiligt.

Aus den identifizierten Treffern werden systematische
Ubersichten von Studien mit gesundheitsokonomischen
Analysen, gesundheitsokonomische Studien bzw. Model-
lierungen zum Vergleich CT-Koronarangiografie vs. inva-
sive Koronarangiografie bei der KHK-Diagnostik fur das
deutsche Gesundheitssystem mit Annahmen aus syste-
matischen Ubersichten ausgewahlt. Als Endpunkte wer-
den Kosten und Kosten-Wirksamkeit berucksichtigt.
Gesundheitsokonomische Bewertungen zu speziellen
Fragestellungen (Bypass- bzw. In-Stent-Restenosen), Ab-
stracts sowie Analysen auf Segmentbasis werden nicht
eingeschlossen. Es werden ausschlieBlich Informations-
quellen zu CT-Geraten mit mindestens 64 Zeilen betrach-
tet. Die Fragestellung, Methodik, Ergebnisse und
Schlussfolgerungen der einzelnen identifizierten gesund-
heitsokonomischen Studien werden beschrieben.
Im Rahmen der gesundheitsokonomischen Modellierung
werden die Gesamtkosten pro Patienten und die Kosten



pro richtig positiv diagnostiziertem Patienten fur die CT-
Koronarangiografie sowie die invasive Koronarangiografie
in Abhangigkeit von der Pratestwahrscheinlichkeit fur
verschiedene Szenarien mit invasiver Koronarangiografie
bzw. intrakoronarer Druckmessungals Referenzstandard
berechnet.

Die bei der Modellierung getroffenen klinischen Annah-
men werden uberwiegend aus der medizinischen Bewer-
tung entnommen (z. B. fur Sensitivitat, Spezifitat). Die
Kosten werden aus der gesellschaftlichen Perspektive
betrachtet und stammen aus aktuellen deutschen Quel-

Lire la suite

• Taille
  253.76 KB
• Nombre de pages
  15