Computed tomography versus exercise testing in suspected coronary artery disease

Invasive coronary angiography is still regarded as the diagnostic standard for
obstructive coronary artery disease (CAD).
However in clinical practice, non-invasive testing is recommended in patients
with suspected chest pain largely because of
safety concerns and costs considerations, partly related to the ability of
functional tests to assess the hemodynamic relevance
of CAD. Due to wide-spread availability and low cost, exercise ECG is
recommended as the initial test, followed by stress
imaging in selected cases.
CT coronary angiography, which lacks many of the drawbacks of invasive catheter
angiography, has emerged as an alternative
(anatomical) test for patients with suspected CAD. While CT has been explored
scientifically and clinically for this purpose over
the past few years, and registry (outcome) data support its value, there is
growing demand for randomized-controlled data to
establish its incremental diagnostic value and economic consequences.
The cardiology community is currently experiencing renewed appreciation for
medical therapy in stable angina, with invasive
diagnostics and therapy reserved for selected patients. On the other hand,
there is an increasing demand for means to identify
individuals at increased risk for adverse cardiovascular events.

We designed a trial to evaluate a new diagnostic approach to suspected CAD with
consideration for the
contemporary insights towards the management of CAD, which incorporates plaque
imaging for prevention of adverse events,
and maintains a role for functional testing when anatomical imaging is
insufficient for medical decision making.
The purpose of this trial is to establish the effectiveness, efficiency and
safety of this new diagnostic workup using cardiac CT in
comparison to the current standard approach to suspected coronary artery
disease.

Study design:
Multi-center, randomized-controlled, clinical efficiency trial, by intention to
diagnose.
After the initial clinical assessment, eligible consenting patients will be
randomized:
1) Standard clinical care based on functional testing according to guidelines
2) Clinical management based on CT imaging.

Recruitment and randomization:
Patients will be screened at the time of referral to the respective out-patient
cardiology clinic, and potentially eligibility patients
will receive documentation before their visit (including baseline
questionnaires). All patients will undergo a comprehensive
history and physical examination, blood analysis and ECG. During their visit
questions regarding the study will be answered
and in case of confirmed eligibility and willingness to participate an
electronic 2:1 randomization will take place.

Investigational CT group:
First a low-dose (<1 mSv) CT scan (64/128-slice dual source CT) without
contrast injection is performed to quantify coronary
calcifications (CCS):
- Negative CCS (and <80% CAD probability): obstructive CAD excluded (est. 37%).
- High CCS (>400): proceed to stress testing because of the high probability of
angiographic CAD and limited discriminative
value of CTA (14%).
- Remaining patients will undergo CTA (+/-50%).

Contrast-enhanced CT (average 5 mSv, heart rate modulation, sublingual
nitroglycerin), will be performed to identify coronary
stenoses and atherosclerotic plaque (CTA):
- Stenosis <50%: obstructive CAD excluded (63%).
- Low-risk obstructive CAD (1-/2-vessel CAD, not being the left main or
proximal LAD) treated with medication, catheter
angiography when symptoms persist (+/-25%).
- High-risk CAD: left main >50%, proximal LAD >70% or 3-vessel CAD referred to
invasive angiography (<10%).
- Non-conclusive CTA (technical failure, borderline disease) for stress testing
(+/-5%).

Patients referred to stress testing (<30%) undergo XECG and/or SPECT perfusion
scintigraphy (MPS) with the same criteria as
the standard care group.
In addition to conventional indications (risk profile, SCORE criteria),
patients with a CCS>400, extensive plaque or >50%
stenosis on CTA will qualify for intensified prevention (lifestyle advise,
medication).
Standard care group
Patients referred to stress testing (<30%) undergo XECG and/or SPECT perfusion
scintigraphy (MPS) with the same criteria as
the standard care group.
In addition to conventional indications (risk profile, SCORE criteria),
patients with a CCS>400, extensive plaque or >50%
stenosis on CTA will qualify for intensified prevention (lifestyle advise,
medication).

Standard care group
XECG and/or myocardial perfusion SPECT (MPS), and invasive angiography if
required, is performed and interpreted in a
protocolized manner, in accordance with international guidelines [7]. Similarly
to the investigational arm, low-risk obstructive
CAD will be treated medically before referral to invasive angiography and/or
revascularization.

Follow-up
Baseline/3/6/12 months:
* Seattle Angina Questionnaire
* Quality of Life rating scale
12 months:
* CBS mortality record
* Telephone interview
* SF-36, EuroQol (quality of life)
* Medical cost, patient costs and productivity
Clinical events will be confirmed by hospital records

Diagnostic intervention with replacement of the stress test by a cardiac CT
scan (in the absence of contra-indications)

Risks:
1) A larger proportion of patients will receive iodine contrast medium. Known
allergies or kidny dysfunction are contraindications to iodine contrast. The
risk of kindeydysfunction is small in patients with a normal kidneyfunction
(which will be checked). Allergic reactions are rare. Medciation and personnel
is available to deal with unexpected reactions. Patients with minimal, or
uncertain reactions in the past will be pre-medicated with H2-antagonists and
corticosteroids. Contrast extravasation can cause skin damage but bis rare and
can be limited by special extravasation detectors.
2) Exposure to radiation is not increased by participation to the study.
3) Although an expected improvement in patient experience and outcome is
expected in the overall population, individual cases of the oposite may occur.
Given the low mortality of chronic coronary disease we expect that the clinical
consequences will be of a minor scale, and (again) will be outbalanced by
individuals in whom better and faster decisicon scould be made based on the CT
result.

Time burden:
There are no significant physical burdens. As a matter of fact many patients
tolerate the CT examninations better than the stress tests.
In terms of time particiaption will take a few hours over 5 years, mostly
related to filling out quyestionnaires.

Benefits & group relatedness:
If the hypothesis is correct, then patients that underwent CT will benefit. In
general, participation to the study benefits similar patients in the future.