The German Federal Joint Committee (G-BA) commissioned the Institute for Quality and Efficiency in Health Care (IQWiG) to assess the benefits and harms of coronary computed tomography angiography (CCTA) in patients with suspected chronic coronary artery disease (CAD) following basic diagnostic tests.
According to the findings of the final report, CCTA has clear advantages for patients as a replacement for other tests in the diagnosis of chronic CAD and can inform decisions about the use of more invasive tests: When compared with functional diagnostic tests without CCTA, such as exercise ECG, and when compared directly with coronary angiography by left heart catheterization (invasive coronary angiography, ICA), IQWiG sees proof of benefit because CCTA can replace the much riskier and invasive ICA and shows some improved treatment outcomes.
However, IQWiG cannot see any benefit or potential of CCTA with the option of subsequent CT-based functional evaluation compared with CCTA without this option. This is because the strategy with the above option carries an additional risk of harm and procedural risks.
A clear diagnosis is essential in CAD
CAD is the leading cause of death in Germany: Deposits in the coronary arteries (atherosclerosis) can lead to narrowing of blood vessels (stenosis) and insufficient blood flow through the heart muscle (insufficient myocardial perfusion), causing chest pain and tightness (angina pectoris). To ensure that chronic CAD is reliably identified and properly treated, a clear diagnosis is essential.
The effects of narrowed blood vessels on myocardial perfusion can be detected by functional diagnostic tests such as stress echocardiography or exercise ECG. The stenoses themselves are detected by morphological tests such as CCTA and ICA, with ICA considered the gold standard for diagnosing chronic CAD. If the result is inconclusive, both can be supplemented with a measurement of function – invasive as part of ICA or with CT as part of CCTA.
Although the current German Disease Management Guideline (Nationale VersorgungsLeitlinie, NVL) strongly discourages ICA in patients with a low and moderate pre-test probability of CAD, the number of ICAs performed in Germany has been steadily increasing for years. For instance, about 510,000 ICAs were performed in 2019. However, in about 30 percent of the medical indications that led to an ICA, there were no pathological findings. A possible reason for the increased use of ICA may be that ICA (with and without measurement of the fractional flow reserve, FFR) is covered by statutory health insurance, whereas CCTA is not.
CCTA with and without CT-based functional evaluation
For the benefit assessment, IQWiG investigated two fundamental questions for patients in whom CAD is suspected following basic diagnostic tests:
- Objective 1 is to assess the benefit of CCTA-based diagnostic strategies compared with diagnostic strategies with the same goal, but without CCTA (e.g. exercise ECG or stress echocardiography or direct ICA).
- Objective 2 is to assess the benefit of CCTA-based diagnostic strategies with the option of additional CT-based functional evaluation of myocardial perfusion compared with diagnostic strategies (possibly including CCTA) without this additional option.
Objective 1: Diagnostic strategy with CCTA compared with diagnostic strategy without CCTA: more benefit and less harm
CCTA-based diagnostic strategies have clear advantages over functional diagnostic tests such as exercise ECG or stress echocardiography: The invasive diagnostic test, ICA, which is only used to rule out chronic CAD, is used less often after CCTA. There is also some evidence CCTA is associated with fewer heart attacks (myocardial infarctions). Disadvantages are only seen in the long term for unstable angina. After analysing the results of 11 studies, IQWiG concluded that, overall there was proof of greater benefit of CCTA-based diagnostic strategies compared with diagnostic strategies using functional diagnostic tests in patients with suspected chronic CAD.
The advantages of CCTA over ICA alone are even clearer. In the four studies included in this comparison, CCTA was performed in the intervention arm before ICA to decide whether to use ICA in the intervention arm, while ICA was always used in the control arm. The studies in this sub-question focused on the appropriateness of CCTA to omit ICA.
The study data showed that patients who were scheduled for ICA but were first assessed with CCTA were much less likely to need further invasive tests. They also had fewer strokes and other serious adverse events. Here too, IQWiG therefore concluded that there was proof of greater benefit of the diagnostic strategy using CCTA compared with direct ICA.
Objective 2: CT-based functional evaluation: no benefit and no potential due to additional risks
For CCTA-based diagnostic strategies with the option of an additional CT-based functional evaluation of myocardial perfusion compared with diagnostic strategies (possibly also CCTA) without this additional option, two different functional diagnostic tests were used as possible add-ons to CCTA in the studies analysed: CT-based measurement of FFR (CT-FFR) and CT-based measurement of myocardial perfusion (CTP).
The results of three studies show that both CT-FFR and CTP as an optional add-on to CCTA contribute to a less invasive diagnostic strategy. However, with one exception, the study results for all other outcomes, such as mortality, angina, state of health, quality of life, and side effects, showed no differences between the groups compared, or no usable data were available.
However, given the noticeably higher number of myocardial infarctions in two study groups where the option of CT-FFR was used, there is concern that the additional procedural options may cause harms that outweigh the potential benefits. The same applies to CTP, which carries additional procedural risks due to the injection of drugs and contrast media and increased radiation exposure.
After weighing all benefits and harms, IQWiG concluded in the final report that there was no benefit of CCTA with the option of CT-based functional evaluation compared with CCTA without this option in patients with suspected chronic CAD. In the preliminary report, IQWiG had initially concluded that the benefits of CT-FFR outweighed the harms based on the studies analysed. Arguments from the comments submitted on the preliminary report regarding the risk of harm led to a change in the conclusion of the final report.
Procedure of report production
IQWiG published the preliminary results, the preliminary report, in February 2023 and invited comments. At the end of the commenting procedure, the project team revised the report and sent it to the contracting agency, the G-BA, as a final report in May 2023, which was published in June 2023. The English translation was published in April 2024. The written comments submitted on the preliminary report were published in a separate document at the same time as the final report.