ONLINE APPENDIX
SUPPLEMENTAL METHODS
Data Quality Control
Matching of patients across databases was performed using medical record number and date of
procedure. Discrepant records were reviewed one by one. Procedures without a vascular access (e.g.,
pericardiocentesis) were removed. Procedures in patients who were not admitted since they were
transferred back to the referring hospital on the same day were also removed, since administrative
discharge data was not available and the incidence of vascular access site complications (VASC)
could not be documented.
Definition of Outcomes
Supplemental Table 1. Operational Definitions of Vascular Access Site Complications (VASC).
Complications
Definitions
Common definitions
Hematoma that forms as the result of a arterial wall discontinuity
and that is contained by the surrounding tissues, confirmed by
Pseudoaneurysm
imaging – diagnosed >24 hours after the procedure (i.e., stable
condition)
Appearance of contrast medium or doppler signal outside the
Arterial perforation
expected real lumen of the vessel, confirmed by imaging –
diagnosed ≤24 hours after the procedure (i.e., unstable condition)
Absence of contrast medium or doppler signal distal to a
Arterial thrombosis
proximally patent vessel, confirmed by imaging
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Appearance of contrast medium or of a doppler signal outside the
Arterial dissection
expected vessel lumen with longitudinal extension (real-andfalse-lumen image), confirmed by imaging
Local access site signs of infection, with or without
Local infection
microbiological or biochemical evidence, or fever
Definition specific to radial access
Major hematoma [1]
Local induration ≥5 cm in the forearm, arm or shoulder
Definitions specific to femoral access
Local induration ≥10 cm measured at the puncture site [2]; ≥5 cm
Major hematoma
if a vascular closure device was used [1,3]
Bleeding into the retroperitoneal space, either confirmed by
Retroperitoneal hematoma
imaging or with the combined occurrence lumbar/abdominal pain,
hemodynamic instability and sudden drop in hemoglobin
Communication between the femoral artery and vein, confirmed
Arterio-venous fistula
by imaging
Ischemia distal to entry site with an entry site that is patent and
Distal embolization
with normal flow, confirmed by imaging
Paresthesia, dysesthesia, hypoesthesia and/or pain that follows
Nerve irritation
nerve distribution
Attributable Risk
The primary objective of this study was to ascertain, at a population level, the fraction of VASC in
femorally-accessed (FA) patients of the contemporary cohort that is attributable to the use of radial
access (RA). To this end, we used the concept of attributable risk, as outlined in Figure 1A [4].
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Attributable risk can be interpreted as the proportion of disease cases over a specified time period that
would be prevented following elimination of the exposure, assuming the exposure is causal [5].
Figure 1. Attributable Risk (AR).
Operationally, to investigate the inverse relationship between RA safety benefits and FA safety
hazards, attributable risks were calculated with the formula shown in Figure 1B. Patients from the
historical cohort were considered as the unexposed group, while FA patients from the contemporary
cohort were considered as the exposed group.
Charlson-Deyo and Elixhauser Comorbidity Indexes
For the Charlson-Deyo comorbidity index (CDCI), we used the scoring system proposed in the original
paper by Charlson et al. [6]. Since a scoring system was not described in the original paper by
Elixhauser et al. [7], for the Elixhauser comorbidity index (ECI) we attributed one point for the
presence of each comorbidity. To account for the change in coding standards between the two study
periods (1996-1998 and 2006-2008), a validated code conversion scheme was used to match the
International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9 CM) coding scheme
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in use during the first period with the International Classification of Diseases, 10th Revision (ICD-10)
coding scheme in use during the second period [8].
Supplemental Table 2. Diseases Included in the Charlson-Deyo and Elixhauser Comorbidity
Indexes.
Charlson-Deyo comorbidity index
Elixhauser comorbidity index
1. Myocardial infarction (1)
1. Congestive heart failure
2. Congestive heart failure (1)
2. Cardiac arrhythmias
3. Peripheral vascular disease (1)
3. Valvular disease
4. Cerebrovascular disease (1)
4. Pulmonary circulation disorders
5. Dementia (1)
5. Peripheral vascular disorders
6. Chronic pulmonary disease (1)
6. Hypertension
7. Rheumatic disease (1)
7. Paralysis
8. Peptic ulcer disease (1)
8. Other neurological disorders
9. Mild liver disease (1)
9. Chronic pulmonary disease
10. Diabetes without chronic complication (1)
10. Diabetes, uncomplicated
11. Diabetes with chronic complication (2)
11. Diabetes, complicated
12. Hemiplegia or paraplegia (2)
12. Hypothyroidism
13. Renal disease (2)
13. Renal failure
14. Any malignancy, including lymphoma and
14. Liver disease
leukemia, except malignant neoplasm of
15. Peptic ulcer disease excluding bleeding
skin (2)
16. Acquired immune deficiency syndrome
15. Moderate or severe liver disease (3)
17. Lymphoma
16. Metastatic solid tumor (6)
18. Metastatic cancer
17. Acquired immune deficiency syndrome /
19. Solid tumor without metastasis
Human immunodeficiency virus (6)
20. Rheumatoid arthritis/collagen vascular
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diseases
21. Coagulopathy
22. Obesity
23. Weight loss
24. Fluid and electrolyte disorders
25. Blood loss anemia
26. Deficiency anemias
27. Alcohol abuse
28. Drug abuse
29. Psychoses
30. Depression
Note: For the CDCI, the scoring system is detailed between parentheses; for liver disease, diabetes
and malignancy, the most severe degree of disease is considered (if a solid tumor with metastasis is
present, score only for metastatic tumor). For the Elixhauser comorbidity index, two points could be
assigned to hypertension depending on the severity of the presentation.
Predictors of Vascular Access Site Complications in the Femoral Contemporary Cohort
To identify the predictors of VASC in the femoral contemporary cohort, we performed univariate
logistic regressions followed by stepwise regression. A p-value <0.20 in univariate regression was
required for a variable to enter the stepwise model and a p-value <0.05 was required to remain in the
final multivariate model. The following variables were considered as candidate predictors: age, sex,
body mass index, type of procedure, access site crossover, vascular closure device, anticoagulant,
use of glycoprotein IIb/IIIa inhibitors, period of the year, ECI and sheath size. The results of these
analyses are outlined in Online Table 2.
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Stratified analyses
We performed several analyses, stratifying VASC rates and attributable risks by:
1. ECI subcategories (0, 1, 2, ≥3): we used these fixed values of ECI when multiplying by the beta
coefficients of the variables included in the model used to calculate adjusted VASC rates. We
subsequently estimated the rates and attributable risks of VASC in the contemporary FA cohort
as compared with the historical cohort, according to ECI subcategories (Figure 3).
2. VASC risk score: we used the beta coefficients of the independent predictors of a VASC
among contemporary FA patients (Online Table 2B), to calculate the baseline risk of a VASC
for subjects in the contemporary FA cohort and historical cohort. We subsequently performed a
stratified analysis to determine the rates and attributable risks of VASC in the contemporary FA
cohort as compared with the historical cohort, according to quartiles of VASC risk (Figure 4).
3. Propensity of undergoing FA in the contemporary cohort: we created a propensity score model
to stratify subjects of the contemporary cohort with similar baseline and procedural
characteristics. The propensity model included: age, gender, body mass index, diabetes,
dyslipidemia, hypertension, smoking, prior history of coronary artery disease, peripheral artery
disease, stroke/TIA, heart failure, CABG and chronic kidney disease, as well as the ECI, the
CDCI, presentation with STEMI, cardiogenic shock, cardiac arrest, type of procedure
(therapeutic vs. diagnostic) and sheath size. The propensity model allowed good balance since
standardized differences between radial and femoral within each stratum were <0.10 in 80% of
cases. We subsequently performed a stratified analysis to determine the rates and attributable
risks of VASC among contemporary FA patients, according to quintiles of the propensity score
of undergoing femoral access, and compared them to the overall VASC rate in the historical
cohort (Figure 5).
References
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