Supplementary data
Table of contents
Randomization
2
Sample size calculation
2
Adjudication and definition of study endpoints
3
SF-36 questionnaire (methods and results)
3
Post-index diagnostic repeated elective diagnostic testing (results)
4
Table 1: Quality of life score at follow-up
5
Table 2: Post-index repeated diagnostic testing during follow-up
6
1
Randomization
After informed consent was obtained, patients were randomized in a 1:1 ratio, to either
coronary computed tomographic angiography (CTA) or standard care based on functional testing. Patients
were assigned with the next consecutive patient study ID, and the randomization office was called to perform
the randomization. A SAS – statistical software generated algorithm was used, including randomization
blocks of 54. Block size and allocation sequence was concealed from the researchers responsible for the
patient enrolment. Neither the investigator responsible for the creation of the randomization sequence nor the
central office performing the randomization was involved in any clinical handling of the patients.
Sample size calculation
Sample size calculation was based on patients’ event rates at Hvidovre Hospital in addition to
previously published data of similar patients presenting to the emergency room with chest pain, no objective
findings and a 19% repeat admission rate with a cardiac adverse event or chest pain within one year. (1)
Since patients with significant coronary artery disease also have risk of a new cardiac event, we found it
reasonable to assume that 20% of the patients in the standard care group would suffer a primary event in the
CATCH trial. The median survival time in the standard care group was estimated to be 37.3 months
[m1=tLN(1/2)/LN(p)], where p is the probability that a patient survives until a specific time point (t). Due to
the established high negative predictive value of coronary CTA, we assumed that the hazard ratio of standard
care to the coronary CTA-guided strategy would be >1.65, and with the initial planned accrual period of 12
months and additional follow-up of 12 months, we would need to include 282 patients in each group, with a
type I error probability for a two sided test of 0.05 and a 80% power level. To reject the null hypothesis the
randomization of 600 patients would then be sufficient.
2
Adjudication and definition of study endpoints
Two dedicated study nurses filled in all events (n=576) into a database. Two experienced cardiologists (KFK
and JDH) performed independent event adjudication in accordance with the definitions of endpoints outlined
below, without knowledge of group allocation. Disagreement in the assessments was solved in consensus
between the two cardiologists.
Cardiac deaths were defined as deaths related to diseases in the heart and unexpected sudden
deaths where a cardiac cause could not be excluded. Acute myocardial infarctions were either ST-elevationMI´s, defined as patients with acute chest pain and persistent (>20 min) ST-segment elevation or Non-STelevation-MI´s defined as a clinical suspicion of acute coronary syndrome and ECG with persistent or
transient ST-segment depression or T-wave inversion, flat T-waves, pseudo-normalization of T waves, or no
ECG changes at presentation. Rise and/or fall in troponins were mandatory for the diagnosis. Hospitalization
for unstable angina pectoris (UAP) was defined as clinical suspicion of acute coronary syndrome requiring
immediate stabilization with medicine and sub-acute invasive coronary angiographic assessment. The ECG
could be normal or mimic that of patients with non-ST-elevation myocardial infarction. Normal troponins
were mandatory. Late symptom-driven revascularization was defined as a late symptom-driven elective ICA,
not related to hospitalization for UAP or MI, requiring treatment with either percutaneous coronary
intervention or coronary artery bypass grafting. Revascularization performed as a consequence of index
diagnostic evaluation was not recorded as an event. Readmission for chest pain was defined as
hospitalization for chest pain in case MI and UAP were ruled out.
SF-36 questionnaire
The SF-36 was designed to measure a general health status divided into eight different subgroups: 1) Physical function - Limitations in physical activities because of health problems; 2) Social
function - Limitations in social activities because of physical or emotional problems; 3) Role physical Limitations in usual role activities because of physical health problems; 4) Bodily pain; 5) Mental function general mental health (psychological distress and well-being); 6) Role Psychological - limitations in usual
role activities because of emotional problems; 7) vitality- (energy and fatigue); and 8) general health
3
perceptions. In addition, the scores of the above mentioned groups are combined in the three overall scores:
Physical health, mental health and total score. Overall, high scores indicate high quality of life. The SF36
quality of life questionnaire was completed by 438 (76%) of the patients at follow-up (table s1).
Post-index repeated elective diagnostic testing
There was no difference in the use of post-index repeated elective diagnostic tests (table s2).
None of the post-index elective invasive coronary angiographies in the coronary CTA-guided group led to
coronary revascularization, whereas one patient in the standard care group, who suffered an MI underwent
PCI at a later stage, and one patient with a normal index bicycle exercise ECG who underwent elective
revascularization.
4
Table 1 : Quality of life score at follow-up
Coronary CTA-
Standard care
P-value
guided
Completed questionnaire
211 (74%)
227 (78%)
0.92
Physical function
90 (65-95)
85 (70-100)
0.59
Social function
88 (75-100)
100 (63-100)
0.94
Role physical
100 (25-100)
100 (25-100)
0.78
Body pain
72 (42-100)
54 (41-100)
0.14
Mental functioning
80 (64-92)
80 (60-92)
0.27
Role psychological
100 (33-100)
100 (33-100)
0.45
Vitality
65 (40-85)
60 (35-80)
0.12
General Health
67 (45-87)
62 (42-77)
0.07
Physical health
71 (47-90)
70 (45-86)
0.28
Mental health
77 (55-91)
76 (52-88)
0.18
Total score
76 (55-92)
74 (52-89)
0.3
Numbers are medians and interquartile ranges
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Table 2: Post-index repeated diagnostic testing during follow-up
Coronary
Standard care
CTA-guided
(N=291)
p-value
(N=285)
13 (5)
11 (4)
0.68
Bicycle exercise ECG, n
2
4
0.69
SPECT, n
4
5
1
Coronary CTA, n
1
0
0.49
ICA, n
7
3
0.87
All, n (%)*
*Number of patients with at least one event. In the coronary CTA-guided group one patient had both bicycle
exercises test and SPECT performed and in the standard care group one patient had both bicycle exercise
ECG and ICA performed.
CTA, computed tomographic angiography; ICA, invasive coronary angiography; SPECT, single photon
emission computed tomography.
References
1.
Prina LD, Decker WW, Weaver AL, High WA, Smars PA, Locke GR III, et al. Outcome of
patients with a final diagnosis of chest pain of undetermined origin admitted under the suspicion of acute
coronary syndrome: a report from the Rochester Epidemiology Project. Ann Emerg Med 2004;43:59–67.
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