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Vascular and Interventional Radiology |
1 From the Program for the Assessment of Radiological Technology (M.C.J.M.K., M.E.A.P.M.A., M.G.M.H.) and the Departments of Radiology (M.C.J.M.K., P.M.T.P., M.G.M.H.), Vascular Surgery (M.R.H.M.v.S., H.v.U.), and Epidemiology & Biostatistics (M.C.J.M.K., M.E.A.P.M.A., T.S., M.G.M.H.), Erasmus Medical Center, Dr Molewaterplein 50, Rm Ee21-40a, 3015 GE Rotterdam, the Netherlands; and the Harvard School of Public Health, Boston, Mass (M.G.M.H.) Received April 4, 2004; revision requested June 16; revision received November 18; accepted December 30. Address correspondence to M.G.M.H. (e-mail: m.hunink{at}erasmusmc.nl).
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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MATERIALS AND METHODS: Institutional medical ethics committee approval and patient informed consent were obtained. Between April 2000 and August 2001, patients with PAD were randomly assigned to undergo either DSA or multi–detector row CT angiography as the initial diagnostic imaging test. Outcomes were the therapeutic confidence assessed by physicians (on a scale from 0 to 10), the need for additional imaging, the health-related quality of life at 6-month follow-up, diagnostic and therapeutic costs, and the costs for a hospital stay. Costs were computed from a hospital perspective according to Dutch guidelines for cost calculations in health care. Mean outcomes were compared between groups with unpaired t testing and were adjusted for predictive baseline characteristics with multivariable regression analysis.
RESULTS: Among the 145 patients, 72 were randomly allocated to the DSA group and 73 to the CT angiography group. One patient in the DSA group had to be excluded. Mean age was 63 years in the DSA group and 64 years in the CT angiography group. There were 47 men in the DSA group and 58 men in the CT angiography group. Physician confidence in making a correct therapeutic choice was significantly higher at DSA (mean confidence score, 8.2) than at CT angiography (mean score, 7.2; P < .001). During 6-month follow-up, 14% less additional imaging was performed in the DSA group than in the CT angiography group (P = .3). No significant quality-of-life differences were found between groups. The diagnostic cost associated with DSA (
564 ± 210 [standard deviation]) was significantly higher than that associated with CT angiography (363 ± 273), a difference of –201 (95% confidence interval: –281, –120; P < .001). Therapeutic and hospitalization costs were similar for both strategies.
CONCLUSION: These results suggest that use of noninvasive multi–detector row CT angiography instead of DSA as the initial diagnostic imaging test for PAD provides sufficient information for therapeutic decision making and reduces imaging costs.
© RSNA, 2005
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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Diagnostic imaging of the peripheral arteries is limited to use in patients for whom a revascularization procedure is contemplated—that is, patients with critical ischemia or with severe disabling intermittent claudication that is unresponsive to exercise therapy. Because the number of revascularization procedures performed to treat PAD is increasing (2) (there was an 8% increase—adjusted for the aging population—in the Netherlands over the past 5 years), the number of preoperative diagnostic imaging procedures is also increasing (3). Diagnostic imaging tests for arterial disease can broadly be classified into noninvasive (or minimally invasive) and invasive vascular tests. The reference standard technique, digital subtraction angiography (DSA), is an invasive technique that requires catheterization of the femoral artery and an intraarterial injection of iodinated contrast medium. It also requires postprocedural observation and, sometimes, hospitalization of the patient. DSA is associated with a higher complication rate (4) and higher costs as compared with noninvasive imaging techniques.
Computed tomographic (CT) angiography is noninvasive, requires only intravenous injection of iodinated contrast medium, and can be performed as an outpatient procedure. The recently introduced multi–detector array technology has overcome the limits of single-section CT scanners. Multi–detector row CT angiography provides high volumetric resolution and total longitudinal coverage of the legs (5,6). A diagnostic work-up with multi–detector row CT angiography as the initial imaging test is potentially less expensive and less of a burden to the patient than a work-up with DSA as the initial test.
Multi–detector row CT angiography has already been shown to be accurate for imaging the peripheral arteries (7–11). The clinical utility and associated costs of and the patient outcomes observed after performing multi–detector row CT angiography instead of DSA in daily practice have, however, not been evaluated. Therefore, the decision as to whether multi–detector row CT angiography should replace DSA in the work-up of PAD remains to be clarified (12,13). Thus, the purpose of our study was to prospectively compare the therapeutic confidence in, the patient outcomes (in terms of quality of life) after, and the costs of DSA with those of multi–detector row CT angiography as the initial diagnostic imaging test in patients with PAD.
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MATERIALS AND METHODS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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Study Population
The institutional medical ethics committee of our tertiary care university hospital (Erasmus MC) approved this study. To be included, eligible patients had to provide written informed consent. Eligible patients had symptomatic PAD and an ankle-brachial systolic blood pressure index of less than 0.90 and had been referred by a vascular surgeon for a diagnostic imaging work-up to evaluate the feasibility of a revascularization procedure. All patients had either severe disabling intermittent claudication that was unresponsive to exercise therapy or critical ischemia. Exclusion criteria were contraindications to angiography, iodinated contrast agents, or revascularization and acute ischemia that required urgent imaging and treatment.
Between April 2000 and August 2001, we approached all eligible patients who were referred from the Department of Vascular Surgery to the Department of Radiology at our university medical center. Baseline characteristics (ie, age, sex, and risk factors) were collected for each patient during the interview at the time of randomization or from the hospital's electronic medical records (M.C.J.M.K.). So that we could evaluate the generalizability of our study, we also prospectively collected baseline characteristics for all patients who were eligible for but who did not participate in the study, and we documented the reasons for nonparticipation (M.C.J.M.K.). Data were analyzed and reported in accordance with the Consolidated Standards of Reporting Trials, or CONSORT, guidelines (14).
Study Design
Patients were randomly allocated to either one of the two diagnostic strategies of interest—DSA or multi–detector row CT angiography as the initial diagnostic imaging test. An independent employee of our university provided a nonstratified computer-generated randomization sequence with a block size of six. The allocation sequence was concealed by means of sealed opaque envelopes that were numbered consecutively. Eligible patients were enrolled by the trial nurses or researchers, who were unaware of the randomization sequence. After randomization, patients and clinicians were not blinded to the imaging strategy because this would have been highly impractical and inconsistent with our goal of performing a pragmatic study.
Diagnostic Imaging and Evaluation
DSA images were acquired by using an image intensifier with a field of view of 38 cm and an acquisition matrix of 512 x 512 pixels with either an Integris V3000 (Philips Medical Systems, Best, the Netherlands) or an Angiostar Plus (Siemens Medical Systems, Forchheim, Germany) system. Catheterization was performed by using a 4-F pigtail catheter (Pigtail; Cordis Europe, Roden, the Netherlands) inserted through a 5-F introducer sheath (Avantis; Cordis Europe) in the asymptomatic common femoral artery. DSA series were obtained at contiguous anatomic levels from the abdominal aorta (at the level just above the renal arteries) down to the level of the ankles. Images were obtained in the anteroposterior projection and were supplemented with additional oblique views when considered necessary. A total of 150–200 mL of nonionic contrast material (iomeprol [300 mg of iodine per milliliter], Iomeron 300; Altana Pharma, Hoofddorp, the Netherlands) was injected at a rate of 10–15 mL/sec for a total of 10–20 mL per series, depending on the position of the catheter tip.
In all patients, the invasive arterial pressure gradients over the left and right iliac arteries were measured by comparing pressure measurements obtained in the aorta (at the catheter tip) with measurements simultaneously obtained in the femoral introducer sheath and in an additional 4-F sheath inserted in the contralateral femoral artery. Pressure measurements were obtained at rest and during pharmacologic vasodilation induced with 60 mg of intraarterial papaverine (Papaverine sulfate CF; Centrafarm, Etten-Leur, the Netherlands). A pressure gradient of more than 10 mm Hg during either rest or vasodilation was considered to indicate the presence of a hemodynamically significant stenosis.
All angiographic procedures were performed by radiology residents in training with the supervision of one of three interventional radiologists (including P.M.T.P.), each of whom had at least 3 years of postresidency experience. The DSA studies were recorded on film for presentation at our institution's weekly vascular conference.
CT angiography was performed with a four–detector row CT scanner (Somatom Plus 4 Volume Zoom; Siemens Medical Systems). A 120-mL volume of iodinated contrast material (iodixanol [320 mg of iodine per milliliter], Visipaque 320; Amersham Health, Eindhoven, the Netherlands) was administered through a 20-gauge cannula in an antecubital vein at a rate of 4 mL/sec. Spiral acquisitions were performed in a single scanning pass from the level of the celiac trunk down to the ankles; patients were asked to hold their breath during the first part of the scanning pass.
The scanning parameters were as follows: pitch of 1.6, 120 kV, 110 mA (effective), and section thickness of 2.5 mm. Scanning was begun at a fixed delay of 25 seconds after the start of contrast material injection, with an average acquisition time of 35 seconds. In patients with a history of decreased cardiac output, a longer delay time was used. The images were reconstructed with an effective section thickness of 3 mm and an increment of 1.5 mm by using the smooth algorithm (B20; Siemens Medical Systems). Three data sets with an overlap of approximately 10 cm were created; each contained approximately 250 images.
All transverse source images were transferred to two online workstations (EasyVision, Philips; and Volume Wizard, Siemens) for the preparation of reconstructions. Sliding maximum intensity projections were obtained with transverse, coronal, and sagittal projections of each data set. Whole-volume maximum intensity projections with segmentation of bone and vessel wall calcifications were obtained. Finally, central lumen line reconstructions through the aortoiliac tract were obtained.
All multi–detector row CT angiography examinations were performed by dedicated CT technologists. Postprocessing reconstructions were performed by dedicated CT technologists and a dedicated researcher with 1 year of general radiology residency training and 1 year of CT angiography experience (M.C.J.M.K.). The CT angiography studies were recorded on film for presentation at the vascular conference. All CT angiograms and DSA images were prospectively interpreted by experienced vascular or interventional radiologists (including P.M.T.P. and M.G.M.H., both with more than 10 years of experience with vascular radiology) and the dedicated researcher (M.C.J.M.K.). The results were reported at the vascular meeting. Results of the stenosis evaluations at multi–detector row CT angiography and DSA are to be published separately.
Therapeutic Confidence and Additional Imaging
Therapeutic confidence was assessed at the weekly vascular conference, where therapeutic decisions were made in consensus by three vascular radiologists and four vascular surgeons. Patient history, physical examination findings, vascular laboratory results, and the findings at the initial imaging test were discussed. Each clinician was asked to rate his or her individual confidence in making a well-founded therapeutic choice with the available diagnostic information. Therapeutic confidence was measured with a 10-point verbal rating scale as part of answering the following question: "How sure are you that you can make an accountable therapeutic choice with the diagnostic information available now? Give a number on a scale ranging from 0 (absolutely uncertain) to 10 (absolutely certain)." The 10-point rating scale was similar to the 10-point school grading system in our country. With this scale, a rating of 5 or lower implies that there is insufficient information to make a therapeutic choice, whereas a rating of 6 or higher implies that there is sufficient information to make a therapeutic choice.
Three radiologists (including P.M.T.P. and M.G.M.H.) and four vascular surgeons (including M.R.H.M.v.S. and H.v.U.) completed the confidence forms during the vascular conferences. Their experience with diagnosing and treating symptomatic PAD varied from 4 to 30 years. The number of physicians who scored a patient's initial images varied from one to five, with a mean of 2.5.
Furthermore, the physicians at the weekly conference determined whether additional imaging tests (duplex ultrasonography [US], DSA, multi–detector row CT angiography, or contrast material–enhanced magnetic resonance [MR] angiography) were necessary. Any additional vascular imaging test performed within 60 days after the initial test or during the 6-month follow-up period was noted. Consensus was always reached with respect to the therapeutic decision (exercise therapy, vascular intervention [percutaneous angioplasty, stent placement, or thrombolysis], or vascular surgery [bypass surgery, endarterectomy, amputation, or aortic bifurcation reconstruction]). The confidence scores, information concerning the need for additional imaging, additional clinical information, and information concerning procedures performed during follow-up were collected during the vascular conference (M.C.J.M.K.).
Quality of Life
Patient outcome was assessed with a self-administered health-related quality-of-life questionnaire that was sent to all patients at the time of randomization and after 3 and 6 months of follow-up. The questionnaires contained the generic EuroQol-5D (EQ-5D) and the generic Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) (15).
The EQ-5D covers five different health dimensions (mobility, self-care, usual activities, pain and discomfort, and anxiety and depression), yielding 243 different health states. For each patient, a single index score was calculated on the basis of a generalized least-squares regression model (16). A single index score of 0 equaled death and a score of 1 equaled maximum health. The EQ-5D index for the entire follow-up period was calculated as the mean of the EQ-5D indexes at 3 and 6 months. Quality-adjusted days were calculated as the integral under the EQ-5D index graph as a function of time.
The SF-36 is a multi-item scale that assesses eight dimensions of the health status of the patient (17). On the basis of results of a previous study, we determined that four of the eight health dimensions (physical functioning, role functioning limitations due to physical problems, bodily pain, and general health perceptions) were relevant to describing health status in PAD (18). We assessed these four dimensions and the answer to one one-item question: change in health during the past year. Each dimension was valued on a 100-point scale, in which 0 indicated poor quality of life and 100 indicated maximum health. The score for each of the SF-36 dimensions for the follow-up period was calculated as the mean score for that dimension at 3 and 6 months.
For each follow-up period, we calculated the response rates for the quality-of-life questionnaires. If one follow-up quality-of-life score was missing, it was imputed. Linear interpolation was used when the quality-of-life score at 3 months was missing, and extrapolation was used when the score at 6 months was missing. The calculations regarding quality of life were performed (M.C.J.M.K.) according to standard rules for item recoding and the treatment of missing items (16,17).
Cost Analysis
For the cost analysis, we collected information (from a hospital perspective) regarding all relevant items related to health care (both diagnostic and therapeutic) used by each patient during the entire trial so that we could calculate the average cost per imaging strategy per patient. The cost of diagnostic imaging included the cost for the initial imaging test and the costs for all additional vascular imaging studies but excluded the cost of the hospital stay for preprocedural work-up and postprocedural observation. The cost of imaging and the cost of percutaneous vascular interventions (percutaneous angioplasty, stent placement, and thrombolysis) were collected prospectively during the performance of these procedures. Surgical costs included costs for vascular surgery (bypass surgery, endarterectomy, amputation, and aortic bifurcation reconstruction).
Costs for hospital stays and outpatient visits during 6 months of follow-up were considered separately. Records of the utilization of these resources were collected from electronic and hard-copy patient medical records, during the vascular conference, and from the patient questionnaires. Because patients were referred to our hospital for tertiary care, all patients underwent their therapy in our hospital. All costs were computed (M.C.J.M.K.) from the hospital perspective according to the Dutch guidelines for cost calculations in health care (19): The cost of primary care, medication costs, "friction costs" (ie, production losses incurred during the time it takes to replace a sick employee), time costs, and travel costs were excluded.
Diagnostic costs included personnel costs; the costs for supplies such as film; the investment costs for the equipment used; costs for equipment servicing; construction costs; and costs for supporting departments, housing, and overhead. Personnel costs were computed by using the measured time spent in performing a diagnostic imaging test or a percutaneous intervention for each involved personnel category and the mean wage rates from our hospital. Social security taxes, including a premium for retirement of 37% of the wage, were added in accordance with national guidelines. The costs for supplies used in diagnostic procedures were based on the sum of the prices of each item used. The annuitized costs of the radiologic equipment and the annual equipment servicing costs were summed and divided by the proportion of the total available room time (80% of a 40-hour work week) (19). Information on the costs of supporting departments was obtained from the records of our Financial and Economics Department. The costs for housing (ie, the rental fees paid by the Department of Radiology to the central administration for the use of floor space) were computed for the involved radiology rooms by multiplying the surface space by the housing cost of 204 per square meter per year. The overhead costs for multi–detector row CT angiography and DSA were estimated to be 15% of the directly assignable costs (19).
The costs of percutaneous vascular interventions were measured and calculated in a similar fashion. For the costs of surgery, we obtained unit costs from the report of another study with a comparable domain and setting (20) that allowed us to calculate an overall cost per patient per surgical procedure. The number of days of hospital stay and the number of hospital visits were collected, and the associated costs were calculated by using national estimates of the costs of hospital stays, intensive care unit stays, and outpatient visits (19). All costs are reported in euros at year 2000 prices (the exchange rate was 84 cents per U.S. dollar in November of 2003). The costs of radiologic equipment (CT scanners, equipment servicing, construction, and contrast agents) were validated by using a small survey of these costs from five different national hospitals (M.C.J.M.K.). Three tertiary care university centers and two secondary care hospitals were interviewed regarding the investment costs of their imaging equipment—specifically, their CT scanners and interventional angiography system(s).
Statistical Analysis
The required sample size was estimated on the basis of the mean estimated strategy costs per patient. To reveal a significant difference between the strategy costs of DSA (estimated to be 520) and the strategy costs of multi–detector row CT angiography (estimated to be 408) with a standard deviation of 180, a power of 0.90, and an 
level of .05, at least 54 patients per strategy would be required. The results were analyzed according to the "intention-to-treat" (here, intention-to-diagnose-and-treat) principle.
We calculated the means (± standard deviations) of the therapeutic confidence scores for the initial imaging test, the number of additional imaging tests performed, the quality-of-life scores at follow-up, the unit costs for the various procedures performed, the diagnostic costs, the therapeutic costs, the costs of hospital stay and outpatient visits, and the total costs for both groups. We assessed the significance of differences between group means with unpaired t tests and calculated 95% confidence intervals (CIs). We used the 
2 test for dichotomous outcomes, the Mann-Whitney test for ordinal outcomes, and the paired t test for equality of mean scores within groups over time.
In addition, we analyzed the differences in all outcomes adjusted for predictive baseline characteristics with multivariable linear and logistic regression. On the basis of results of previous studies (21) and our clinical experience, we assumed that the severity of disease (critical ischemia vs claudication) and the presence of renal insufficiency, cerebrovascular disease, or diabetes mellitus at baseline were potentially predictive of the outcomes. In analyzing the improvement in quality of life during follow-up, we also adjusted for the baseline quality-of-life scores.
Furthermore, multivariable linear and logistic regression was used to analyze the trends in therapeutic confidence, the use of additional imaging tests, and costs over time during the trial period. For therapeutic confidence, the trend in the results was illustrated by a comparison of means between the first and the last 7 months of the study period. We expressed time by the number of days between the start of the trial and the randomization of the patient. The outcome of interest was the dependent variable. The independent variables included time, group allocation, and their interaction term. A one-way sensitivity analysis was performed for the investment in radiology equipment by using a range (ie, ±33% of the equipment investment) for the life expectancy of radiologic equipment and a reduction of 3 years (rather than the 10 years of a base-case scenario) and was performed for the costs of housing by using an increase of 100%.
A P value of .01 was considered to indicate a statistically significant difference for the quality-of-life outcomes and the costs because of multiple testing. For other tests, a significance level of .05 was used.
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RESULTS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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Within 60 days after the initial test, 11 patients in the DSA group and 22 patients in the multi–detector row CT angiography group underwent additional imaging tests (P = .04). With adjustment for predictive variables at baseline and the trial period, a similar result was found. During the total follow-up of 6 months, 17 patients in the DSA group and 31 patients in the CT angiography group underwent additional imaging tests (P = .02). In the DSA group, seven patients underwent one additional test, while 22 patients in the CT angiography group underwent one additional test. Eight patients in both groups underwent two tests, one patient in both groups underwent three tests, and one patient in the DSA group underwent four additional imaging tests (P = .06). On average, fewer additional imaging tests per patient were performed in the DSA group than in the CT angiography group (0.42 vs 0.56; difference, 14%; 95% CI: –14%, 30%; P = .3). We observed a small decrease in the number of additional imaging tests performed during the trial period, but this trend was not significant (P = .12), and there was no difference in the trend between the groups (P = .3).
Quality of Life
The response rate for the quality-of-life questionnaires was 91% (131 of 144 questionnaires) at baseline, 68% (98 of 144 questionnaires) at 3 months, and 63% (91 of 144 questionnaires) at 6 months of follow-up.
The quality of life assessed with the EQ-5D questionnaire at baseline and at follow-up was not significantly different between the two groups. The improvement in the EQ-5D index from baseline to follow-up (Table 2) was slightly larger in the CT angiography group (0.11; 95% CI: 0.01, 0.21) than in the DSA group (0.07; 95% CI: –0.02, 0.16), but there was no statistically significant difference between the groups both without and with adjustment for baseline scores and potentially predictive variables.
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The mean quality of life assessed with the SF-36 was not significantly different between the groups at baseline and at follow-up. The improvement in SF-36 dimensions from baseline to follow-up (Table 2) was not statistically significant for the DSA group: The largest improvement occurred in the dimension "health change" (mean score improvement, 8 points; 95% CI: –2, 18). In the CT angiography group, however, a significant improvement from baseline to follow-up was observed for three dimensions—physical functioning (mean score improvement, 9 points; 95% CI: 3, 16; P = .006), bodily pain (mean score improvement, 11 points; 95% CI: 3, 19; P = .006), and health change (mean score improvement, 12 points; 95% CI: 3, 21; P = .007). With and without adjustment for baseline scores and predictive variables, we found a slightly larger improvement in quality of life for all SF-36 dimensions in the CT angiography group (Table 2), but this improvement was not statistically significant.
Cost Analysis
The mean unit cost of the individual imaging tests (excluding imaging-related hospital stays) was 526 for all DSA examinations (range, 493–568 with sensitivity analysis) and 203 for all multi–detector row CT angiography examinations (range, 185–233) (Table 3). For the additional imaging tests, the mean unit cost was 429 (range, 367–509) for all contrast-enhanced MR angiography tests and 37 for all duplex US tests (range, 35–40).
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564 ± 210 per patient in the DSA group and 363 ± 273 per patient in the multi–detector row CT angiography group; this represents a significant cost reduction, with a difference of –201 (95% CI: –281, –120; P < .001; Table 4). This reduction was achieved in spite of the fact that more additional imaging tests were performed after multi–detector row CT angiography than after DSA. With adjustment for predictive variables, a similar cost reduction was demonstrated (–174; 95% CI: –267, –82; P < .001).
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527 to 610 for the DSA group and from 333 to 402 for the CT angiography group.
The number of treatment procedures performed was similar for each type of procedure for both groups. One-third of the patients in each group were assigned to undergo walking exercise therapy. The mean cost for all percutaneous vascular interventions for PAD was similar between the groups (difference, 3; 95% CI: –354, 361; Table 4). With adjustment for predictive variables, the average cost for percutaneous interventions was 152 (95% CI: –196, 500) higher in the CT angiography group than in the DSA group. The average cost for surgical procedures was lower in the CT angiography group (–181; 95% CI: –972, 610). With adjustment for predictive variables, this cost difference was –968 (95% CI: –1957, 20).
The cost of hospital admission and outpatient visits for PAD was 2206 (95% CI: 214, 4197) higher in the CT angiography group, which was not a statistically significant difference when the multiple comparisons that we performed were considered (P = .03). In three patients, all of whom were in the CT angiography group, the cost of the hospital stay and hospital visits was more than 28000 (eight times more than the average cost). After adjustment for predictive variables at baseline (in this case, disease severity [critical ischemia vs claudication], renal insufficiency, cerebrovascular disease, and diabetes mellitus), the cost for hospital admission and outpatient visits was only 428 (95% CI: –1587, 2443) higher in the CT angiography group.
The total costs were 1827 (95% CI: –604, 4259) higher in the CT angiography group. With adjustment for predictive variables, the situation reversed, and the total costs were higher in the DSA group (562; 95% CI: –3218, 2094), but the differences with and without adjustment were not significant.
Over time during the trial, the trends in costs for diagnostic tests, percutaneous interventions, surgical procedures, and hospital stays and the trends in total costs were not statistically significant; these trends were also not significantly different between the groups.
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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Use of multi–detector row CT angiography resulted in lower but in most cases sufficient therapeutic confidence than use of the current reference standard, DSA. Despite the fact that it led to more additional imaging, the use of multi–detector row CT angiography reduced the diagnostic costs for the imaging work-up and did not result in discernible additional therapeutic costs or costs for hospital stays and visits. Furthermore, there was no loss in quality of life compared with the quality of life after DSA—in fact, a slightly larger improvement during follow-up in all quality-of-life measures was found for the CT angiography group. Our results suggest that DSA can be replaced by multi–detector row CT angiography as the initial imaging test for the evaluation of PAD before revascularization.
We found that therapeutic confidence with DSA was higher than that with multi–detector row CT angiography. However, the therapeutic confidence with CT angiography was shown to be sufficient to enable therapeutic decisions in the majority of cases. When confidence was insufficient after DSA or CT angiography, additional imaging could be performed to increase physician confidence in making a well-founded clinical decision. We found that physicians requested additional imaging tests for patients in the CT angiography group more frequently than they did for patients in the DSA group, presumably owing to the lower degree of confidence in multi–detector row CT angiography.
Low confidence in CT angiography occurred particularly in cases of extensive vessel wall calcifications. A calcified vessel wall indicates severe disease, but this feature can be an impediment to stenosis measurement (22) and, therefore, can result in a lower confidence score. DSA has the advantage that it can provide hemodynamic information for the stenosis; this information is often used as the ultimate standard in clinical practice. When physicians were uncertain about the degree of a stenosis depicted at multi–detector row CT angiography, DSA was performed to verify the degree of stenosis with pressure measurements. Nevertheless, even though additional testing was needed for confident therapeutic decision making for some patients who were imaged with multi–detector row CT angiography, the additional cost needed to provide sufficient information in those cases in which CT angiography did not provide enough information on its own was less than the extra cost needed to perform DSA as the standard procedure in everyone. In other words, a diagnostic pathway beginning with multi–detector row CT angiography is less costly overall than one beginning with DSA, despite the higher rate of additional imaging tests needed. The confidence in therapeutic decisions made on the basis of results of these imaging tests is considered in more detail in Adriaensen et al (23).
The results of the quality-of-life questionnaires revealed no statistically significant differences in patient outcomes between the two groups. This suggests that multi–detector row CT angiography is likely to have accurately identified PAD, as is to be expected, given the investigations that have shown multi–detector row CT angiography to be accurate (7–11). As a general rule, if the interventional radiologist and the vascular surgeon were unable to determine the extent and location of disease correctly by using multi–detector row CT angiography and additional testing as needed, the patient would not have been treated correctly, and his or her symptoms would probably have remained or worsened, which would have been reflected by a lower quality of life during follow-up. In fact, patients in the multi–detector row CT angiography group reported a slightly larger gain in quality of life during follow-up. This could imply that patients who underwent multi–detector row CT angiography had a slight advantage, but, because the CT angiography group had a lower reported quality of life at baseline, they also had more to gain with treatment. We adjusted the improvements in quality of life for the baseline scores and potentially predictive variables and found that the difference in improvement was even larger in favor of the multi–detector row CT angiography group but was still not significant.
The mean diagnostic cost in the multi–detector row CT angiography group was lower than that in the DSA group, even though additional imaging was performed more frequently in the CT angiography group during the total follow-up period. This is explained by the lower costs of the initial imaging test. Multi–detector row CT angiography is less expensive than DSA owing to lower investment, supply, and personnel costs.
The use of multi–detector row CT angiography as the initial test did not alter clinical decisions with respect to treatment of symptomatic PAD in any major way. This is reflected by the fact that, after adjustment, we found no difference in therapeutic costs between the two arms of the study. The data on therapeutic costs, however, should be interpreted with caution because our study lacked the power to enable strong conclusions in this area.
The unadjusted mean cost for hospital stays and visits was found to be 2206 lower for the DSA group, but the difference between the two groups was not statistically significant. Severity of disease (critical ischemia vs claudication), renal insufficiency, cerebrovascular disease, and diabetes mellitus increased the cost of hospital stays and visits substantially, and, with adjustment for these predictive baseline variables, the large difference in costs between the DSA and multi–detector row CT angiography groups disappeared. It seems plausible that when wound healing is hampered (eg, because of diabetes mellitus) or when mobilization is difficult (eg, because of cerebrovascular disease), the duration of the hospital stay and the degree of necessary care increase, and, therefore, the cost of hospital stays and visits increases.
In fact, three patients had extremely high costs related to their hospital admission and outpatient visits. At baseline all three patients had critical ischemia and a history of cerebrovascular disease, cardiac disease, diabetes mellitus, smoking, hyperlipidemia, and hypertension; additionally, one of these patients had severe renal insufficiency. Thus, all three had an extremely poor clinical status before randomization, and their recovery and rehabilitation were therefore long and costly. Although these three patients were in the multi–detector row CT angiography arm of the study, it seems highly unlikely that the high costs were the result of the choice of initial imaging modality—these patients would probably have amassed similar hospital costs if they had been randomized to the DSA group.
Because the results of all vascular imaging tests in our hospital are always discussed before revascularization at the weekly interdisciplinary vascular conference, we were able to trace all randomized and nonrandomized eligible patients. One reason for nonrandomization was the clinical absence of femoral pulsations, which would have made femoral catheterization impossible. Although brachial catheterization may have been possible, this involves an increased risk (4). Multi–detector row CT angiography is a safe and robust alternative to DSA in such cases and was used to evaluate these patients. The baseline characteristics of the randomized and the nonrandomized patients were comparable, indicating that bias in the selection of the patients was unlikely. This indicates that our results can be generalized to the entire population of patients who have intermittent claudication or critical limb ischemia at presentation and have no contraindications to multi–detector row CT angiography.
Reports of comparative studies have indicated that multi–detector row CT angiography has a sensitivity for evaluation of the complete peripheral arterial system that ranges between 91% and 92%, a specificity that ranges between 92% and 97%, and an agreement with DSA that ranges between 78% and 92% (7,9,10). These results are, however, difficult to translate into patient outcomes and patient care decisions; such translation would require either a decision analysis or a randomized controlled trial (12). Randomized controlled trials are not frequently used to compare diagnostic tests (24–30). Contrary to what opponents of randomized controlled trials argue (13,31), we found this present pragmatic randomized trial to be both feasible and inexpensive.
Limitations of our study included the lack of all data for one patient, who therefore could not be included in the analysis (32). Although patients were randomized, baseline characteristics could have biased the outcomes in both a situation in which there was a large imbalance in baseline characteristics, each with a small effect on outcome, and in a situation in which there was a minor imbalance in baseline characteristics, each with a strong effect on outcome. Therefore, multivariable linear and logistic regression was used to adjust for potentially predictive variables (33–35).
Furthermore, the clinicians could not be blinded to group allocation because the images produced at multi–detector row CT angiography and those produced at DSA are clearly different. Subjective attitudes may have influenced the scoring of therapeutic confidence, but we attempted to adjust for this by normalizing the scores across physicians. A possible shortcoming was that we focused on quality of life as a measure of effectiveness and did not assess functional outcomes such as the ankle-brachial systolic blood pressure index or walking distance. Although quality-of-life outcomes are sometimes perceived to be "soft data" because of their subjectivity (as opposed to outcomes that provide quantitative "hard data"), they do reflect the outcome most important to the patient. In this, our study is consistent with the recommendations given by the recent TransAtlantic Inter-Society Consensus on PAD (21), which state that quality of life is the most important primary study end point.
Although the therapeutic and hospital costs varied considerably between individual patients in our study population—some patients underwent exercise therapy, while others underwent expensive interventional or surgical revascularizations or experienced a delayed recovery or a need for prolonged rehabilitation—no significant differences between the groups could be demonstrated. A study with a larger sample size, however, would be necessary to reveal differences in therapeutic costs or make equivalence plausible.
Another important limitation of our study is that the costs reported may be unique to our institution and thus not applicable to other settings. Because our cost estimates could be subject to the setting, we compared them with costs at two other national university hospitals and two national private hospitals. We found our costs to be within the range of costs in other settings. Furthermore, we analyzed the effect of uncertainty in the cost estimates by performing a one-way sensitivity analysis. Varying the costs of equipment (the life-years of equipment, the costs of construction, and the costs of housing) did not affect our conclusions. In addition, in our clinic, all patients first undergo diagnostic imaging, whereas in other settings, percutaneous intervention may immediately follow DSA in the same session when warranted.
We make exceptions to our protocol only in emergency situations, when a patient may be treated directly after diagnostic DSA, but this was an exclusion criterion for our study. Our vascular surgeons and interventional radiologists prefer to discuss each case at the weekly conference with the entire team and carefully choose and plan treatment. The costs of the DSA strategy would have been reduced if diagnosis and therapy had been combined in a single session where possible. It is impossible to predict whether this would have yielded enough of a cost reduction to reverse the conclusions of this study. The amount of any such reduction would depend strongly on the percentage of patients who might undergo a combined diagnostic and treatment session and on the average reduction in cost per patient, which would vary from hospital to hospital.
Furthermore, in calculating the diagnostic imaging costs, we excluded the costs of the hospital stay for the preprocedural work-up and postprocedural observation because we chose to focus on the costs incurred by the radiology department for this cost outcome; this exclusion resulted in an underestimation of the actual cost difference between DSA and multi–detector row CT angiography. In spite of this underestimation, we still found the difference to be statistically significant. Finally, because costs were analyzed from the hospital perspective, the cost of primary care, patient costs, friction costs, time costs, travel costs, and the cost of medication supplied outside the hospital were excluded. We did not expect that these costs would differ between the two groups because thrombocyte aggregation inhibitors and lipid-lowering medication are standard treatments for patients with atherosclerosis.
In comparison with other noninvasive techniques, multi–detector row CT angiography can depict the entire arterial system of the legs, is inexpensive, and is a fast and robust scanning technique. Furthermore, multi–detector row CT angiography is rapidly becoming widely available. Other noninvasive techniques (ie, duplex US and contrast-enhanced MR angiography) have the advantage of not involving radiation, but this advantage should be assessed in relation to the age of the population of patients with PAD. Although duplex US has proved to be useful in the evaluation of selected arterial segments, assessment of the entire lower extremity arterial tree remains an arduous task, is associated with a lower sensitivity and specificity, and does not provide a "road map" (20). Contrast-enhanced MR angiography is increasingly being used in patients with PAD—especially those with chronic renal insufficiency. MR angiography is, however, not widely available and requires expensive equipment investments, skilled personnel, and more time for imaging.
The results of our randomized trial suggest that it is feasible to replace DSA with multi–detector row CT angiography as the initial imaging test for the evaluation of PAD. As compared with the use of DSA as the initial imaging test, the use of multi–detector row CT angiography as the initial imaging test for the evaluation of PAD yields sufficient information for decision making; reduces imaging costs; leads to similar costs for therapy, hospital stays, and outpatient visits; and leads to similar degrees of quality-of-life improvement.
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ACKNOWLEDGMENTS |
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FOOTNOTES |
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Abbreviations: CI = confidence interval • DSA = digital subtraction angiography • EQ-5D = EuroQol-5D • PAD = peripheral arterial disease • SF-36 = Medical Outcomes Study 36-Item Short Form Health Survey
2 Current address: Department of Radiology, University Medical Center Utrecht, the Netherlands 
See Materials and Methods for pertinent disclosures
Author contributions: Guarantor of integrity of entire study, M.G.M.H.; study concepts, M.C.J.M.K., M.G.M.H.; study design, M.C.J.M.K., T.S., M.G.M.H.; literature research, M.C.J.M.K.; clinical studies, M.C.J.M.K., M.E.A.P.M.A., M.R.H.M.v.S., H.v.U., P.M.T.P., M.G.M.H.; data acquisition, M.C.J.M.K., M.E.A.P.M.A., M.R.H.M.v.S., H.v.U., P.M.T.P., M.G.M.H.; data analysis/interpretation, M.C.J.M.K., T.S., M.G.M.H.; statistical analysis, M.C.J.M.K., T.S.; manuscript preparation and editing, M.C.J.M.K.; manuscript definition of intellectual content, revision/review, and final version approval, all authors
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= Seven patients in the DSA group and eight patients in the multi–detector row CT angiography (MDCTA) group underwent both percutaneous intervention and a surgical procedure. DUS = Doppler US.