- Email: [email protected]
Health-related quality-of-life outcomes after open versus endovascular abdominal aortic aneurysm repair
REVIEW ARTICLES Richard P. Cambria, MD, Section Editor From the Canadian Society for Vascular Surgery
Health-related quality-of-life outcomes after open versus endovascular abdominal aortic aneurysm repair Ahmed Kayssi, MD, MSc, MPH,a Ann DeBord Smith, MD, MPH,b Graham Roche-Nagle, MD, MBA,a and Louis L. Nguyen, MD, MBA, MPH,c Toronto, Ontario, Canada; and Boston, Mass Objective: Endovascular repair (EVAR) of abdominal aortic aneurysms is a safe alternative to open aneurysm repair (OAR) in selected patients. The aim of this study was to compare the health-related quality-of-life (HR-QoL) outcomes of patients following EVAR and OAR. Methods: A literature search of PubMed, EMBASE, and the Cochrane Library identified five randomized trials that reported on HR-QoL in EVAR and OAR for elective management of infrarenal abdominal aortic aneurysms. No consistent HR-QOL instrument was used among the studies. A meta-analysis was performed on the 36-Item Short Form (SF-36) and the EuroQol-5D (EQ-5D) HR-QoL results. Results: SF-36 general health scores were higher for EVAR at 3, 6, and 12 months postoperatively. SF-36 physical functioning scores were higher for EVAR at 6 months but this advantage was lost at 12 months. In addition, SF-36 social functioning scores were higher for EVAR at 12 months. SF-36 component summary scores were not significantly different. EVAR was associated with a better EQ-5D score at 3, 6, and 12 months, but not at 24 months of follow-up. Conclusions: EVAR was associated with better HR-QoL in some domains up to 12 months postoperatively. There is insufficient data to demonstrate a HR-QoL advantage beyond 12 months. More studies are required to examine any longterm HR-QoL advantages for either intervention. (J Vasc Surg 2015;62:491-8.)
Abdominal aortic aneurysms (AAA) are a potentially lethal condition that is more prevalent in men and has been reported in up to 10% of patients aged 80 to 85 years.1 Current treatment options for AAA include surveillance and operative repair in selected patients. Commonly performed interventions include conventional open aneurysm repair (OAR)2 and endovascular stent placement (EVAR).3 Laparoscopic AAA repair has also been described but is currently not a widely available treatment modality.4 As medical institutions continue to search for ways of maximizing the value of healthcare delivery, patientFrom the Division of Vascular Surgery, University of Toronto, Torontoa; the Center for Surgery and Public Health, Brigham and Women’s Hospital,b and Division of Vascular and Endovascular Surgery, Brigham and Women’s Hospital,c Harvard Medical School, Boston. Author conflict of interest: none. Presented as a poster at the Thirty-fourth Annual Meeting of the Canadian Society for Vascular Surgery, Quebec City, Quebec, Canada, September 28-29, 2012. Correspondence: Dr Ahmed Kayssi, Toronto General Hospital, University Health Network, Eaton North Wing, 6th Floor Rm 6EN216, 200 Elizabeth St, Toronto, ON, M5G 2C4, Canada (e-mail: ahmed.kayssi@mail. utoronto.ca). The editors and reviewers of this article have no relevant financial relationships to disclose per the JVS policy that requires reviewers to decline review of any manuscript for which they may have a conflict of interest. 0741-5214 Copyright Ó 2015 by the Society for Vascular Surgery. Published by Elsevier Inc. http://dx.doi.org/10.1016/j.jvs.2015.05.032
centered outcomes research has emerged as an important adjuvant to traditional clinical research. Today’s patients, backed by internet searches and online support communities, expect their physicians to prescribe the safest, most effective, and the least disruptive interventions for their quality of life. Health-related quality-of-life (HR-QoL) research helps address those patient concerns by characterizing and quantifying patient perspectives on their treatment. Several HR-QoL instruments have been used to assess vascular surgery patient satisfaction and health perceptions before and after aortic surgery. Two validated HR-QoL instruments that have been previously used in vascular surgery patients are the Short Form 36 (SF-36)5 and EuroQol 5D (EQ-5D), also now known as EQ-5D-3 L.6 The SF-36 and EQ-5D are generic questionnaires that have been validated in multiple countries and languages and are relatively easy to complete and interpret. The SF-36 generates a patient profile based on eight self-reported scales: physical and social functioning, role-physical and role-emotional, general and mental health, bodily pain, and vitality.7 Each scale is scored between 0 and 100, and the eight scales can then be used to generate physical and mental health summary measures. Conversely, the EQ-5D is based on five self-reported scales: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression.8 These “self-classification” responses can then be used to generate an index score along a scale where 1 represents best possible health and 0 represents death.9 491
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Table I. MEDLINE, Embase, and Cochrane Database of Systematic Reviews search strategies and results Number
Search terms
Results
MEDLINE 1 Aortic Aneurysm, Abdominal[mesh] OR “abdominal aortic aneurysm”[tiab] OR “abdominal aorta aneurysm”[tiab] 2 “endovascular”[tw] OR evar[tiab] 3 “Randomized Controlled Trials” 4 1 and 2 and 3 Embase 1 exp abdominal aorta aneurysm/ 2 abdominal aortic aneurysm.mp. 3 abdominal aorta aneurysm.mp. 4 exp endovascular surgery/or endovascular.mp. 5 exp controlled clinical trial/ 6 1 or 2 or 3 7 4 and 5 and 6
Search terms Cochrane Database of Systematic Reviews “abdominal aortic aneurysm” OR “abdominal aorta aneurysm” in Title, Abstract, or Keywords “endovascular” OR “EVAR” in Title, Abstract, or Keywords
15,684 25,999 444,521 170 18,816 12,012 18,861 39,530 490,053 20,828 238
Cochrane reviews
Other reviews
12
47
29
90
The aim of this study was to review the literature for evidence of differences in short- and long-term HR-QoL outcomes between elective patients who have undergone EVAR vs OAR. METHODS Protocol and eligibility criteria. Our study included all published randomized trials in the English language that reported HR-QoL outcomes following EVAR or OAR for the elective management of AAA. To minimize the risk of bias, we did not include studies of ruptured AAA, observational, or non-randomized studies. The study protocol followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines.10 Information sources and search and study selection. The electronic databases MEDLINE, Embase, and the Cochrane Systematic Reviews Database were searched for all available online records up to August 10, 2013. The search strategies and number of records obtained for all three databases are detailed in Table I. Two reviewers screened the abstracts obtained from all three databases independently and agreed on the abstracts that met the inclusion criteria. The studies that did not meet the inclusion criteria or did not report HR-QOL outcomes were excluded. The selected studies were then reviewed for any relevant publications that were not captured by the initial search.
Data collection process. The data was extracted independently from the selected studies. Attempts were made to contact study authors to obtain the primary HR-QoL data but were only successful in one instance (Soulez et al11). Data items. The data extracted for every study included baseline study population mean age and gender distribution, the study’s country, year of publication, and the SF-36 summary and component scores and EQ-5D data collected at 3, 6, 12 and 24 months, if reported in the study. A previously described and validated prediction model was used to derive mean EQ-5D scores from the eight SF-36 domain scores for studies where EQ-5D data was not collected.12 Risk of bias. The risk of bias between and within studies was assessed using the Cochrane Collaboration’s Risk of Bias Tool.13 All the studies were assessed independently by two reviewers (A.K. and A.D.S.) in six domains: adequate randomization sequence generation, allocation concealment, blinding of outcomes, strategy for addressing missing data, and freedom from selective reporting, as well as any other sources of potential bias. Studies were given a score of yes, no, or unclear for each of those six domains. The software Review Manager v.5 (Cochrane Collaboration, Oxford)14 was used to generate a risk of bias table. Synthesis of results. The summary measure generated in this study was the standard difference in means (SDM). This allowed the inclusion of SF-36 and EQ-5D data that was reported as either a mean change from the baseline or as actual mean scores at various time-points. SF-36 and EQ-5D data from individual studies were pooled in a weighted fashion, and a standard difference in means with a 95% confidence interval (CI) was generated. A randomeffects model was used to calculate the summary measures due to the variation in publication years, EVAR stents, and country of origin between the studies. Betweentrial heterogeneity was assessed using the c2 test. Publication bias was assessed by generating funnel plots that were visually inspected for symmetry. All data synthesis and subsequent analysis was carried out using the software Comprehensive Meta-Analysis v.2 (Biostat, New York). RESULTS Study selection. The online database search identified 588 records and two additional reports were identified from review of the included studies (Fig 1). We excluded 424 studies after reviewing the abstracts, and the remaining 14 articles were assessed for eligibility. Of those, five were excluded because they did not report HR-QoL outcomes, and four were unsuitable because they reported on patients with ruptured AAA or compared EVAR to surveillance. Five studies met our full inclusion criteria.11,15-18 Study characteristics. The characteristics of the five included studies are shown in Table II. Three of those studies were from Europe and two from North America. A total of 2232 patients were included in the analysis (95% male; average age, 71 years). The studies were published between 2004 and 2009. No consistent HR-QoL instrument was used, but most studies reported SF-36 component or domain scores or the EQ-5D index.
Identification
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Records idenƟfied through database searching (n = 586)
AddiƟonal records idenƟfied through other sources (n = 2)
Screening
Records aŌer duplicates removed (n = 442)
Eligibility
Records excluded (n = 424)
Full-text arƟcles assessed for eligibility (n = 14 )
Included
Records screened (n = 442)
Studies included in qualitaƟve and quanƟtaƟve synthesis (meta-analysis) (n = 5)
Full-text arƟcles excluded (n=5 HR-QOL not measured) (n=2 Ruptured aneurysms) (n=2 EVAR vs. Surveillance)
Fig 1. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram. EVAR, Endovascular aneurysm repair; HR-QOL, health-related quality of life.
Table II. Characteristics of included studies Males
Study
Year
Country
DREAM12 2004 Netherlands 13
EVAR-1 Lottman14 Soulez8 OVER
2004 2004 2005 2009
No.
%
No.
Quality-of-life instruments
Age, years EVAR OAR
SF-36 component summaries
SF-36 all domains EQ-5D
141 92
70.2
77
76
No
Yes
Yes
United Kingdom 983 91 Netherlands 70 92 Canada 39 98 United States 876 99
74.1 68.8 70.8 70.0
543 57 20 444
539 19 20 437
Yes No No Yes
No Yes Yes No
Yes No No Yes
Follow-up Weeks: 3, 6 Months: 3, 6, 12 Months: 1-3, 3-12, 12-24 Months: 1, 3 Months: 1, 6, >12 Months: 12, 24
DREAM, Dutch Randomised Endovascular Aneurysm Management Study; EQ-5D, EuroQol-5D; EVAR, endovascular aneurysm repair; EVAR 1, Endovascular Aneurysm Repair Study; OAR, open aneurysm repair; OVER, Open Versus Endovascular Repair Study; SF-36, short form-36.
SF-36 analysis. A meta-analysis of the SF-36 component summaries and individual domain scores was carried out (Table III). Meta-analysis of mental component summaries (comprising of the vitality, social functioning, role-emotional, and mental health scales) and physical component summaries (comprising of physical functioning,
role-physical, bodily pain, and general health scales) was also carried out. At 12 months, there was no statistically significant difference between the OAR and EVAR mental component (standard difference in the means [SDM], 0.058; P ¼ .645) and physical component summaries (SDM, 0.017; P ¼ .732) in the Open Versus Endovascular
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Table III. Meta-analysis of the standard difference in means between open aneurysm repair (OAR) and endovascular aneurysm repair (EVAR) short form-36 (SF-36) domains at 3, 6, and 12 months 3 Months Domain Body pain General health Mental health Physical functioning Emotional role functioning Physical role functioning Social functioning Vitality score
6 Months
12 Months
Standard difference in means
P
Standard difference in means
P
Standard difference in means
P
0.157 0.432 0.079 0.238 0.079 0.204 0.051 0.112
.238 .004 .552 .075 .556 .127 .705 .403
0.159 0.432 0.203 0.333 0.092 0.101 0.061 0.252
.295 .005 .183 .029 .545 .518 .688 .098
0.248 0.41 0.15 0.268 0.197 0.148 0.356 0.198
.102 .01 .323 .077 .193 .329 .019 .193
Negative result favors EVAR.
Repair (OVER) and Endovascular Aneurysm Repair (EVAR-1) studies. There was also no difference at 24 months between the mental (SDM, 0.026; P ¼ .631) and physical component summaries (SDM, 0.004; P ¼ .937). The results of the individual SF-36 domain analyses are demonstrated at 3 and 6 months (Dutch Randomised Endovascular Aneurysm Management [DREAM], Soulez, and Lottman studies) and 12 months (DREAM and Soulez studies) in Table III. At 3 months, EVAR patients had higher general health scores compared with OAR (SDM, 0.432; P ¼ .004), but the two groups were otherwise not different. At 6 months, EVAR patients still had higher scores in general health (SDM, 0.432; P ¼ .005) and now also higher scores in physical functioning (SDM, 0.333; P ¼ .029). At 12 months, the higher general health (SDM, 0.41; P ¼ .01) scores persisted for EVAR patients, while social functioning scores (SDM, 0.356; P ¼ .019) were also higher for EVAR patients. There was no statistically significant difference between any of the other domains. EQ-5D analysis. The results of the EQ-5D analyses are demonstrated in Fig 2. EVAR was associated with a higher score at 3, 6, and 12 months when analyzing EQ5D data reported by the studies (DREAM, EVAR-1, and OVER) or calculated using the prediction model (Lottman and Soulez). However, this advantage for EVAR was not present at 24 months. Heterogeneity and risk of bias. The c2 test showed no significant between-trial heterogeneity in the SF-36 and EQ-5D analyses at the P ¼ .05 level. Funnel plots generated for EQ-5D data at different time points suggested negative study publication bias (Fig 3). Moreover, while the studies had a low risk of selection bias, all the studies were found to be at high risk of performance and detection bias because of lack of blinding of participants and outcome assessors (Fig 4). This lack of blinding can lead to systematic differences in the care and outcomes between the two intervention groups. DISCUSSION The goal of this study was to assess any differences in QoL outcomes after OAR vs EVAR for the elective surgical
management of infrarenal AAA. Our study suggests that EVAR is associated with better HR-QoL in some domains up to 12 months postoperatively. There is insufficient data, however, to suggest an advantage for either treatment modality after 12 months. The short-term advantage for EVAR over OAR has similarly been demonstrated in allcause perioperative as well as AAA-related mortality.19 However, this advantage was lost after 2 years of followup, similar to the loss of QoL advantage seen in our study beyond 12 months. Previous studies comparing QoL outcomes after open and minimally invasive surgery have similarly reported no long-term advantage for either approach in colectomies,20 hysterectomies,21 or nephrectomies.22 Our study is the first to utilize the model developed and validated by Ara and colleagues to predict EQ-5D scores from individual SF-36 domain scores in patients who have undergone aortic surgery.12 Two limitations facing HR-QoL research in vascular surgery are the lack of validated disease-specific survey instruments for open and endovascular aortic interventions, and the variation in HR-QoL instruments used by investigators in the different studies that have compared OAR and EVAR. Furthermore, neither the SF-36 nor the EQ-5D has been validated specifically in aortic surgery patients. By converting SF-36 domain data to EQ-5D data, we were able to compare a larger number of studies and draw more rigorous conclusions about HR-QoL outcomes after OAR and EVAR. While the SF-36 and EQ-5D have both been widely used to measure HR-QoL outcomes in vascular surgery, previous studies in other patient populations have demonstrated that the two instruments do not always correlate.23,24 Employing both instruments thus permits a more comprehensive analysis of HR-QoL outcomes in our patient population. Furthermore, unlike the SF-36, EQ-5D data can be used to calculate quality-adjusted life years, which are useful in evaluating the economic impact of medical interventions.8 Our findings are different from those reported by Coughlin and colleagues, who pooled SF-36 data from 16 studies to examine pre- and postoperative HR-QoL outcomes of OAR vs EVAR up to 1 year.25 Those authors
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a Study name Outcome
Sample size
Std diff in means and 95% CI
Std diff in means p-Value EVAR OAR DREAM EVAR 1 Lottman Soulez
EQ-5D EQ-5D EQ-5D EQ-5D
-0.079 -0.260 -0.061 -0.577 -0.226
0.645 0.005 0.828 0.086 0.003
73 238 52 20
65 245 17 17 -1.00 -0.50
0.00
0.50
1.00
Favors EVAR Favors OAR
b
Study name Outcome
Sample size
Std diff in means and 95% CI
Std diff in means p-Value EVAR OAR DREAM Soulez
EQ-5D EQ-5D
-0.485 -0.361 -0.459
0.005 0.283 0.003
74 19
65 17 -1.00 -0.50
0.00
0.50
1.00
Favors EVAR Favors OAR
c
Study name Outcome
Sample size
Std diff in means and 95% CI
Std diff in means p-Value EVAR OAR DREAM EVAR-1 OVER Soulez
EQ-5D EQ-5D EQ-5D EQ-5D
-0.493 -0.083 -0.121 -0.739 -0.212
0.004 0.217 0.078 0.035 0.022
73 476 429 19
68 414 421 16 -1.00 -0.50
0.00
0.50
1.00
Favors EVAR Favors OAR
d
Study name Outcome
Sample size
Std diff in means and 95% CI
Std diff in means p-Value EVAR OAR EVAR-1 OVER Soulez
EQ-5D EQ-5D EQ-5D
-0.041 0.057 -0.401 -0.001
0.572 0.452 0.322 0.985
398 350 12
371 348 13 -1.00 -0.50
0.00
0.50
1.00
Favors EVAR Favors OAR Fig 2. Meta-analysis of the standard difference in means between open aneurysm repair (OAR) and endovascular repair (EVAR) EuroQol-5D (EQ-5D) scores at 3 (a), 6 (b), 12 (c), and 24 months (d). Negative result favors EVAR. CI, Confidence interval; DREAM, Dutch Randomised Endovascular Aneurysm Management Study; EVAR 1, Endovascular Aneurysm Repair Study; std diff, standard difference.
reported an advantage for EVAR over OAR in the SF-36 domains of vitality and physical role functioning at 3 months. No significant differences, however, were found between SF-36 domains for EVAR and OAR after 3 months. Conversely, we report an advantage for EVAR over OAR in the SF-36 general health domain at 3, 6, and 12 months postoperatively. We report a similar
advantage for EVAR in physical functioning at 6 months and social functioning at 12 months. Coughlin and colleagues did not report on EQ-5D outcomes, whereas we demonstrated an advantage for EVAR when considering EQ-5D outcomes for up to 12 months. The differences between our findings and those reported by Coughlin and colleagues might be explained by our different study
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Fig 3. Funnel plot for EuroQol-5D (EQ-5D) studies at 12 months. Absence of studies in the right lower area under the funnel suggests publication bias against studies favoring open aneurysm repair (OAR). std diff, Standard difference.
inclusion criteria. As mentioned earlier, we chose to limit our analysis to randomized controlled trials that specifically compared HR-QoL outcomes between OAR and EVAR, whereas Coughlin’s study also included nonrandomized cohort studies and studies including an observational arm. Moreover, Coughlin and colleagues did not include in their meta-analysis a randomized controlled trial by Soulez’ group that reported an advantage in certain SF-36 domains among EVAR patients.11 The short-term HR-QoL advantage for EVAR over OAR could be explained by the avoided laparotomy and longer hospital stay that are inherent with OAR. One would expect the EVAR patient who is discharged home on the first postoperative day with small groin incisions to report a higher HR-QoL satisfaction than the patient undergoing OAR. Our findings suggest, however, that this advantage lasts up to 1 year, which suggests that the differences go beyond the immediate wound healing issues to include a longer recovery period needed for patients who undergo major operations. While none of the studies included in our analysis followed patients beyond 2 years (Table II), we have shown that, beyond 1 year, the differences in QoL are no longer present. Reasons for this might include issues unique to EVAR such as endoleak and the need for long term surveillance among EVAR patients. Furthermore, long-term HR-QoL measures can be diluted by other nonaneurysm related issues affecting the elderly patients in this population. While we have demonstrated an advantage in HR-QoL outcomes for EVAR over OAR for up to 12 months, the extent to which either the SF-36 or the EQ-5D questionnaires are responsive to changes among OAR and EVAR patients is unclear. Because of the general nature of those questionnaires, they might not be able to detect small
changes in HR-QoL outcomes unique to patients with aortic disease before or after undergoing open or endovascular interventions. This may explain why we found no difference between SF-36 summary scores but a significant difference between some of the SF-36 domains. It also highlights the need for a disease-specific HR-QoL instrument developed specifically for this patient population, similar to previously developed instruments such as the Claudication Scale (CLAU-S)26 or the Edinburgh Claudication Questionnaire (ECQ)27 for claudicants. The clinical relevance of our findings lies in its qualitative rather than quantitative clinical implications: that there is a significant postoperative quality-of-life advantage favoring EVAR in EQ-5D and in several SF-36 domains, but that this advantage is lost at 1 year of follow-up. Our study is not without limitations. We are limited by the small number of trials that were included in the analysis. We chose to restrict our analysis to randomizedcontrolled trials that directly compared HR-QoL outcomes between OAR and EVAR. We excluded trials of EVAR in small aneurysms (such as the Comparison of Surveillance vs Aortic Endografting for Small Aneurysm Repair [CAESAR] trial28) or trials that compared EVAR with surveillance (such as the EVAR-2 trial29) because the study design and study inclusion criteria are different from the trials directly comparing OAR and EVAR. We have also identified a possible publication bias against HR-QoL trials favoring OAR vs EVAR. However, a search of the online clinical trial registry, clinicaltrials.gov, did not suggest that any registered trials comparing HR-QoL outcomes between EVAR or OAR were not published, which suggests that our findings can be explained by the small number of studies included in our analysis rather than a genuine publication bias. Given the proven safety and effectiveness
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surgical team.30 However, this would not have been feasible or practical in trials comparing open and endovascular abdominal aortic aneurysm repair. Blinded patients are less likely to have biased psychological or physical responses to intervention or to seek additional adjunct interventions.31 Moreover, blinded trial investigators are less likely to transfer their views to patients or to administer extra interventions.31 It is unclear, however, what effect, if any, this lack of blinding had on the estimation of the true difference in HR-QoL outcomes between the two treatment modalities. Finally, the generalizability of our results will be impacted by the advent of newer EVAR stents and deployment techniques and the increasing uptake of EVAR among vascular surgeons. This will likely affect the rate of intra- and postoperative complications and, ultimately, the patient HR-QoL outcomes. This limitation, however, is inherent to all studies that analyze evolving technologies. These limitations notwithstanding, our study represents a contemporary comprehensive meta-analysis of HR-QoL outcomes in patients undergoing abdominal aneurysm interventions. Because no universally accepted HR-QoL instrument was used in these trials, our validated conversion methods allowed for direct comparison of results from different trials. Our study also highlights the current diversity of approaches to utility measurement among vascular researchers, as well as the usefulness of having a standardized instrument such as the EQ-5D for conducting economic analyses on today’s plethora of emerging technologies. CONCLUSIONS
Fig 4. Cochrane risk of bias summary: Review authors’ judgements about each risk of bias item for each included study. Green circle, low risk of bias; red circle, high risk of bias; empty square, unclear risk of bias. DREAM, Dutch Randomised Endovascular Aneurysm Management Study; EVAR 1, Endovascular Aneurysm Repair Study; OVER, Open Versus Endovascular Repair Study.
EVAR is associated with better HR-QoL for up to 1 year postoperatively, but the advantage is not seen at 2 years. More studies are required, however, to examine any long-term HR-QoL advantages for either intervention, especially in light of the need for continued surveillance of EVAR patients. The authors would like to thank Dr Paul Bain for his help with searching the literature and Dr George Tomlinson for his guidance with meta-analysis methodology. AUTHOR CONTRIBUTIONS
of endovascular abdominal aortic interventions and the current lack of clinical equipoise regarding their use among vascular surgeons, it is unlikely that future trials will be conducted to compare the effectiveness of open vs endovascular abdominal aortic aneurysm repair, which could allow for more HR-QoL data to be gathered and analyzed. As such, we are limited by the available data from previously conducted trials. We have identified a high risk of performance and detection bias, both of which stem from a lack of blinding, in all of the included studies. This remains a significant challenge in surgical trials and may be mitigated by the introduction of sham operations or the use of a second
Conception and design: AK, LN Analysis and interpretation: AK, AS, GR-N, LN Data collection: AK, AS Writing the article: AK, AS, GR-N, LN Critical revision of the article: AK, AS, GR-N, LN Final approval of the article: AK, AS, GR-N, LN Statistical analysis: AK Obtained funding: Not applicable Overall responsibility: LN REFERENCES 1. Bengtsson H, Sonesson B, Bergqvist D. Incidence and prevalence of abdominal aortic aneurysms, estimated by necropsy studies and population screening by ultrasound. Ann NY Acad Sci 1996;800:1-24.
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2. Dubost C, Allary M, Oeconomos N. Resection of an aneurysm of the abdominal aorta: reestablishment of the continuity by a preserved human arterial graft, with result after five months. AMA Arch Surg 1952;64:405-8. 3. Parodi JC, Palmaz JC, Barone HD. Transfemoral intraluminal graft implantation for abdominal aortic aneurysms. Ann Vasc Surg 1991;5: 491-9. 4. Economopoulos KP, Martinou E, Hakimian S, Schizas D, Georgopoulos S, Tsigris C, et al. An overview of laparoscopic techniques in abdominal aortic aneurysm repair. J Vasc Surg 2013;58: 512-20. 5. Patel AA, Donegan D, Albert T. The 36-item short form. J Am Acad Orthop Surg 2007;15:126-34. 6. EuroQol Group. EuroQolea new facility for the measurement of health-related quality of life. Health Policy 1990;16:199-208. 7. Ware JE Jr. SF-36 health survey update. Spine 2000;25:3130-9. 8. Dyer MT, Goldsmith KA, Sharples LS, Buxton MJ. A review of health utilities using the EQ-5D in studies of cardiovascular disease. Health Qual Life Outcomes 2010;8:13. 9. Rabin R, de Charro F. EQ-5D: a measure of health status from the EuroQol Group. Ann Med 2001;33:337-43. 10. Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gotzsche PC, Ioannidis JP, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. J Clin Epidemiol 2009;62: e1-34. 11. Soulez G, Therasse E, Monfared AA, Blair JF, Choiniere M, Elkouri S, et al. Pain and quality of life assessment after endovascular versus open repair of abdominal aortic aneurysms in patients at low risk. J Vasc Interv Radiol 2005;16:1093-100. 12. Ara R, Brazier J. Deriving an algorithm to convert the eight mean SF-36 dimension scores into a mean EQ-5D preference-based score from published studies (where patient level data are not available). Value Health 2008;11:1131-43. 13. Higgins JP, Altman DG, Sterne JA, editors. Chapter 8: Assessing risk of bias in included studies. Cochrane handbook for systematic reviews of interventions. The Cochrane Collaboration; 2011. 5.1.0 [updated March 2011] ed. 14. Review Manager (RevMan) [Computer program]. Version 5.2 ed. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration; 2012. 15. Prinssen M, Verhoeven EL, Buth J, Cuypers PW, Van Sambeek MR, Balm R, et al. A randomized trial comparing conventional and endovascular repair of abdominal aortic aneurysms. N Engl J Med 2004;351:1607-18. 16. Comparison of endovascular aneurysm repair with open repair in patients with abdominal aortic aneurysm (EVAR trial 1), 30-day operative mortality results: randomised controlled trial. Lancet 2004;364:843-8. 17. Lottman PE, Laheij RJ, Cuypers PW, Bender M, Buth J. Healthrelated quality of life outcomes following elective open or endovascular
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29.
30. 31.
AAA repair: a randomized controlled trial. J Endovasc Ther 2004;11: 323-9. Lederle FA, Freischlag JA, Kyriakides TC, Padberg FT Jr, Matsumura JS, Kohler TR, et al. Outcomes following endovascular vs open repair of abdominal aortic aneurysm: a randomized trial. JAMA 2009;302:1535-42. Dangas G, O’Connor D, Firwana B, Brar S, Ellozy S, Vouyouka A, et al. Open versus endovascular stent graft repair of abdominal aortic aneurysms: a meta-analysis of randomized trials (Structured abstract). Database of Abstracts of Reviews of Effects [serial on the Internet]. 2012. Available at: http://onlinelibrary.wiley.com/o/cochrane/ cldare/articles/DARE-12012050583/frame.html. Accessed February 2, 2015. Theodoropoulos GE, Karantanos T. Quality of life after laparoscopic colectomy for cancer. JSLS 2014;18:225-35. de la Orden SG, Reza MM, Blasco JA, Andradas E, Callejo D, Perez T. Laparoscopic hysterectomy in the treatment of endometrial cancer: a systematic review. J Minim Invasive Gynecol 2008;15:395-401. Becker A, Pradel L, Kluth L, Schmid M, Eichelberg C, Ahyai S, et al. Laparoscopic versus open partial nephrectomy for clinical T1 renal masses: no impact of surgical approach on perioperative complications and long-term postoperative quality of life. World J Urol 2014;33:421-6. Myers C, Wilks D. Comparison of Euroqol EQ-5D and SF-36 in patients with chronic fatigue syndrome. Qual Life Res 1999;8:9-16. McDonough CM, Grove MR, Tosteson TD, Lurie JD, Hilibrand AS, Tosteson AN. Comparison of EQ-5D, HUI, and SF-36-derived societal health state values among spine patient outcomes research trial (SPORT) participants. Qual Life Res 2005;14:1321-32. Coughlin PA, Jackson D, White AD, Bailey MA, Farrow C, Scott DJ, et al. Meta-analysis of prospective trials determining the short- and mid-term effect of elective open and endovascular repair of abdominal aortic aneurysms on quality of life. Br J Surg 2013;100:448-55. Marquis P, Comte S, Lehert P. International validation of the CLAU-S quality-of-life questionnaire for use in patients with intermittent claudication. Pharmacoeconomics 2001;19:667-77. Leng GC, Fowkes FG. The Edinburgh Claudication Questionnaire: an improved version of the WHO/Rose Questionnaire for use in epidemiological surveys. J Clin Epidemiol 1992;45:1101-9. Cao P, De Rango P, Verzini F, Parlani G, Romano L, Cieri E. Comparison of surveillance versus aortic endografting for small aneurysm repair (CAESAR): results from a randomised trial. Eur J Vasc Endovasc Surg 2011;41:13-25. Endovascular aneurysm repair and outcome in patients unfit for open repair of abdominal aortic aneurysm (EVAR trial 2): randomised controlled trial. Lancet 2005;365:2187-92. Gurusamy KS, Gluud C, Nikolova D, Davidson BR. Assessment of risk of bias in randomized clinical trials in surgery. Br J Surg 2009;96:342-9. Schulz KF, Grimes DA. Blinding in randomised trials: hiding who got what. Lancet 2002;359:696-700.
Submitted Feb 7, 2015; accepted May 14, 2015.
Health-related quality-of-life outcomes after open versus endovascular abdominal aortic aneurysm repair Ahmed Kayssi, MD, MSc, MPH,a Ann DeBord Smith, MD, MPH,b Graham Roche-Nagle, MD, MBA,a and Louis L. Nguyen, MD, MBA, MPH,c Toronto, Ontario, Canada; and Boston, Mass Objective: Endovascular repair (EVAR) of abdominal aortic aneurysms is a safe alternative to open aneurysm repair (OAR) in selected patients. The aim of this study was to compare the health-related quality-of-life (HR-QoL) outcomes of patients following EVAR and OAR. Methods: A literature search of PubMed, EMBASE, and the Cochrane Library identified five randomized trials that reported on HR-QoL in EVAR and OAR for elective management of infrarenal abdominal aortic aneurysms. No consistent HR-QOL instrument was used among the studies. A meta-analysis was performed on the 36-Item Short Form (SF-36) and the EuroQol-5D (EQ-5D) HR-QoL results. Results: SF-36 general health scores were higher for EVAR at 3, 6, and 12 months postoperatively. SF-36 physical functioning scores were higher for EVAR at 6 months but this advantage was lost at 12 months. In addition, SF-36 social functioning scores were higher for EVAR at 12 months. SF-36 component summary scores were not significantly different. EVAR was associated with a better EQ-5D score at 3, 6, and 12 months, but not at 24 months of follow-up. Conclusions: EVAR was associated with better HR-QoL in some domains up to 12 months postoperatively. There is insufficient data to demonstrate a HR-QoL advantage beyond 12 months. More studies are required to examine any longterm HR-QoL advantages for either intervention. (J Vasc Surg 2015;62:491-8.)
Abdominal aortic aneurysms (AAA) are a potentially lethal condition that is more prevalent in men and has been reported in up to 10% of patients aged 80 to 85 years.1 Current treatment options for AAA include surveillance and operative repair in selected patients. Commonly performed interventions include conventional open aneurysm repair (OAR)2 and endovascular stent placement (EVAR).3 Laparoscopic AAA repair has also been described but is currently not a widely available treatment modality.4 As medical institutions continue to search for ways of maximizing the value of healthcare delivery, patientFrom the Division of Vascular Surgery, University of Toronto, Torontoa; the Center for Surgery and Public Health, Brigham and Women’s Hospital,b and Division of Vascular and Endovascular Surgery, Brigham and Women’s Hospital,c Harvard Medical School, Boston. Author conflict of interest: none. Presented as a poster at the Thirty-fourth Annual Meeting of the Canadian Society for Vascular Surgery, Quebec City, Quebec, Canada, September 28-29, 2012. Correspondence: Dr Ahmed Kayssi, Toronto General Hospital, University Health Network, Eaton North Wing, 6th Floor Rm 6EN216, 200 Elizabeth St, Toronto, ON, M5G 2C4, Canada (e-mail: ahmed.kayssi@mail. utoronto.ca). The editors and reviewers of this article have no relevant financial relationships to disclose per the JVS policy that requires reviewers to decline review of any manuscript for which they may have a conflict of interest. 0741-5214 Copyright Ó 2015 by the Society for Vascular Surgery. Published by Elsevier Inc. http://dx.doi.org/10.1016/j.jvs.2015.05.032
centered outcomes research has emerged as an important adjuvant to traditional clinical research. Today’s patients, backed by internet searches and online support communities, expect their physicians to prescribe the safest, most effective, and the least disruptive interventions for their quality of life. Health-related quality-of-life (HR-QoL) research helps address those patient concerns by characterizing and quantifying patient perspectives on their treatment. Several HR-QoL instruments have been used to assess vascular surgery patient satisfaction and health perceptions before and after aortic surgery. Two validated HR-QoL instruments that have been previously used in vascular surgery patients are the Short Form 36 (SF-36)5 and EuroQol 5D (EQ-5D), also now known as EQ-5D-3 L.6 The SF-36 and EQ-5D are generic questionnaires that have been validated in multiple countries and languages and are relatively easy to complete and interpret. The SF-36 generates a patient profile based on eight self-reported scales: physical and social functioning, role-physical and role-emotional, general and mental health, bodily pain, and vitality.7 Each scale is scored between 0 and 100, and the eight scales can then be used to generate physical and mental health summary measures. Conversely, the EQ-5D is based on five self-reported scales: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression.8 These “self-classification” responses can then be used to generate an index score along a scale where 1 represents best possible health and 0 represents death.9 491
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Table I. MEDLINE, Embase, and Cochrane Database of Systematic Reviews search strategies and results Number
Search terms
Results
MEDLINE 1 Aortic Aneurysm, Abdominal[mesh] OR “abdominal aortic aneurysm”[tiab] OR “abdominal aorta aneurysm”[tiab] 2 “endovascular”[tw] OR evar[tiab] 3 “Randomized Controlled Trials” 4 1 and 2 and 3 Embase 1 exp abdominal aorta aneurysm/ 2 abdominal aortic aneurysm.mp. 3 abdominal aorta aneurysm.mp. 4 exp endovascular surgery/or endovascular.mp. 5 exp controlled clinical trial/ 6 1 or 2 or 3 7 4 and 5 and 6
Search terms Cochrane Database of Systematic Reviews “abdominal aortic aneurysm” OR “abdominal aorta aneurysm” in Title, Abstract, or Keywords “endovascular” OR “EVAR” in Title, Abstract, or Keywords
15,684 25,999 444,521 170 18,816 12,012 18,861 39,530 490,053 20,828 238
Cochrane reviews
Other reviews
12
47
29
90
The aim of this study was to review the literature for evidence of differences in short- and long-term HR-QoL outcomes between elective patients who have undergone EVAR vs OAR. METHODS Protocol and eligibility criteria. Our study included all published randomized trials in the English language that reported HR-QoL outcomes following EVAR or OAR for the elective management of AAA. To minimize the risk of bias, we did not include studies of ruptured AAA, observational, or non-randomized studies. The study protocol followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines.10 Information sources and search and study selection. The electronic databases MEDLINE, Embase, and the Cochrane Systematic Reviews Database were searched for all available online records up to August 10, 2013. The search strategies and number of records obtained for all three databases are detailed in Table I. Two reviewers screened the abstracts obtained from all three databases independently and agreed on the abstracts that met the inclusion criteria. The studies that did not meet the inclusion criteria or did not report HR-QOL outcomes were excluded. The selected studies were then reviewed for any relevant publications that were not captured by the initial search.
Data collection process. The data was extracted independently from the selected studies. Attempts were made to contact study authors to obtain the primary HR-QoL data but were only successful in one instance (Soulez et al11). Data items. The data extracted for every study included baseline study population mean age and gender distribution, the study’s country, year of publication, and the SF-36 summary and component scores and EQ-5D data collected at 3, 6, 12 and 24 months, if reported in the study. A previously described and validated prediction model was used to derive mean EQ-5D scores from the eight SF-36 domain scores for studies where EQ-5D data was not collected.12 Risk of bias. The risk of bias between and within studies was assessed using the Cochrane Collaboration’s Risk of Bias Tool.13 All the studies were assessed independently by two reviewers (A.K. and A.D.S.) in six domains: adequate randomization sequence generation, allocation concealment, blinding of outcomes, strategy for addressing missing data, and freedom from selective reporting, as well as any other sources of potential bias. Studies were given a score of yes, no, or unclear for each of those six domains. The software Review Manager v.5 (Cochrane Collaboration, Oxford)14 was used to generate a risk of bias table. Synthesis of results. The summary measure generated in this study was the standard difference in means (SDM). This allowed the inclusion of SF-36 and EQ-5D data that was reported as either a mean change from the baseline or as actual mean scores at various time-points. SF-36 and EQ-5D data from individual studies were pooled in a weighted fashion, and a standard difference in means with a 95% confidence interval (CI) was generated. A randomeffects model was used to calculate the summary measures due to the variation in publication years, EVAR stents, and country of origin between the studies. Betweentrial heterogeneity was assessed using the c2 test. Publication bias was assessed by generating funnel plots that were visually inspected for symmetry. All data synthesis and subsequent analysis was carried out using the software Comprehensive Meta-Analysis v.2 (Biostat, New York). RESULTS Study selection. The online database search identified 588 records and two additional reports were identified from review of the included studies (Fig 1). We excluded 424 studies after reviewing the abstracts, and the remaining 14 articles were assessed for eligibility. Of those, five were excluded because they did not report HR-QoL outcomes, and four were unsuitable because they reported on patients with ruptured AAA or compared EVAR to surveillance. Five studies met our full inclusion criteria.11,15-18 Study characteristics. The characteristics of the five included studies are shown in Table II. Three of those studies were from Europe and two from North America. A total of 2232 patients were included in the analysis (95% male; average age, 71 years). The studies were published between 2004 and 2009. No consistent HR-QoL instrument was used, but most studies reported SF-36 component or domain scores or the EQ-5D index.
Identification
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Records idenƟfied through database searching (n = 586)
AddiƟonal records idenƟfied through other sources (n = 2)
Screening
Records aŌer duplicates removed (n = 442)
Eligibility
Records excluded (n = 424)
Full-text arƟcles assessed for eligibility (n = 14 )
Included
Records screened (n = 442)
Studies included in qualitaƟve and quanƟtaƟve synthesis (meta-analysis) (n = 5)
Full-text arƟcles excluded (n=5 HR-QOL not measured) (n=2 Ruptured aneurysms) (n=2 EVAR vs. Surveillance)
Fig 1. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram. EVAR, Endovascular aneurysm repair; HR-QOL, health-related quality of life.
Table II. Characteristics of included studies Males
Study
Year
Country
DREAM12 2004 Netherlands 13
EVAR-1 Lottman14 Soulez8 OVER
2004 2004 2005 2009
No.
%
No.
Quality-of-life instruments
Age, years EVAR OAR
SF-36 component summaries
SF-36 all domains EQ-5D
141 92
70.2
77
76
No
Yes
Yes
United Kingdom 983 91 Netherlands 70 92 Canada 39 98 United States 876 99
74.1 68.8 70.8 70.0
543 57 20 444
539 19 20 437
Yes No No Yes
No Yes Yes No
Yes No No Yes
Follow-up Weeks: 3, 6 Months: 3, 6, 12 Months: 1-3, 3-12, 12-24 Months: 1, 3 Months: 1, 6, >12 Months: 12, 24
DREAM, Dutch Randomised Endovascular Aneurysm Management Study; EQ-5D, EuroQol-5D; EVAR, endovascular aneurysm repair; EVAR 1, Endovascular Aneurysm Repair Study; OAR, open aneurysm repair; OVER, Open Versus Endovascular Repair Study; SF-36, short form-36.
SF-36 analysis. A meta-analysis of the SF-36 component summaries and individual domain scores was carried out (Table III). Meta-analysis of mental component summaries (comprising of the vitality, social functioning, role-emotional, and mental health scales) and physical component summaries (comprising of physical functioning,
role-physical, bodily pain, and general health scales) was also carried out. At 12 months, there was no statistically significant difference between the OAR and EVAR mental component (standard difference in the means [SDM], 0.058; P ¼ .645) and physical component summaries (SDM, 0.017; P ¼ .732) in the Open Versus Endovascular
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Table III. Meta-analysis of the standard difference in means between open aneurysm repair (OAR) and endovascular aneurysm repair (EVAR) short form-36 (SF-36) domains at 3, 6, and 12 months 3 Months Domain Body pain General health Mental health Physical functioning Emotional role functioning Physical role functioning Social functioning Vitality score
6 Months
12 Months
Standard difference in means
P
Standard difference in means
P
Standard difference in means
P
0.157 0.432 0.079 0.238 0.079 0.204 0.051 0.112
.238 .004 .552 .075 .556 .127 .705 .403
0.159 0.432 0.203 0.333 0.092 0.101 0.061 0.252
.295 .005 .183 .029 .545 .518 .688 .098
0.248 0.41 0.15 0.268 0.197 0.148 0.356 0.198
.102 .01 .323 .077 .193 .329 .019 .193
Negative result favors EVAR.
Repair (OVER) and Endovascular Aneurysm Repair (EVAR-1) studies. There was also no difference at 24 months between the mental (SDM, 0.026; P ¼ .631) and physical component summaries (SDM, 0.004; P ¼ .937). The results of the individual SF-36 domain analyses are demonstrated at 3 and 6 months (Dutch Randomised Endovascular Aneurysm Management [DREAM], Soulez, and Lottman studies) and 12 months (DREAM and Soulez studies) in Table III. At 3 months, EVAR patients had higher general health scores compared with OAR (SDM, 0.432; P ¼ .004), but the two groups were otherwise not different. At 6 months, EVAR patients still had higher scores in general health (SDM, 0.432; P ¼ .005) and now also higher scores in physical functioning (SDM, 0.333; P ¼ .029). At 12 months, the higher general health (SDM, 0.41; P ¼ .01) scores persisted for EVAR patients, while social functioning scores (SDM, 0.356; P ¼ .019) were also higher for EVAR patients. There was no statistically significant difference between any of the other domains. EQ-5D analysis. The results of the EQ-5D analyses are demonstrated in Fig 2. EVAR was associated with a higher score at 3, 6, and 12 months when analyzing EQ5D data reported by the studies (DREAM, EVAR-1, and OVER) or calculated using the prediction model (Lottman and Soulez). However, this advantage for EVAR was not present at 24 months. Heterogeneity and risk of bias. The c2 test showed no significant between-trial heterogeneity in the SF-36 and EQ-5D analyses at the P ¼ .05 level. Funnel plots generated for EQ-5D data at different time points suggested negative study publication bias (Fig 3). Moreover, while the studies had a low risk of selection bias, all the studies were found to be at high risk of performance and detection bias because of lack of blinding of participants and outcome assessors (Fig 4). This lack of blinding can lead to systematic differences in the care and outcomes between the two intervention groups. DISCUSSION The goal of this study was to assess any differences in QoL outcomes after OAR vs EVAR for the elective surgical
management of infrarenal AAA. Our study suggests that EVAR is associated with better HR-QoL in some domains up to 12 months postoperatively. There is insufficient data, however, to suggest an advantage for either treatment modality after 12 months. The short-term advantage for EVAR over OAR has similarly been demonstrated in allcause perioperative as well as AAA-related mortality.19 However, this advantage was lost after 2 years of followup, similar to the loss of QoL advantage seen in our study beyond 12 months. Previous studies comparing QoL outcomes after open and minimally invasive surgery have similarly reported no long-term advantage for either approach in colectomies,20 hysterectomies,21 or nephrectomies.22 Our study is the first to utilize the model developed and validated by Ara and colleagues to predict EQ-5D scores from individual SF-36 domain scores in patients who have undergone aortic surgery.12 Two limitations facing HR-QoL research in vascular surgery are the lack of validated disease-specific survey instruments for open and endovascular aortic interventions, and the variation in HR-QoL instruments used by investigators in the different studies that have compared OAR and EVAR. Furthermore, neither the SF-36 nor the EQ-5D has been validated specifically in aortic surgery patients. By converting SF-36 domain data to EQ-5D data, we were able to compare a larger number of studies and draw more rigorous conclusions about HR-QoL outcomes after OAR and EVAR. While the SF-36 and EQ-5D have both been widely used to measure HR-QoL outcomes in vascular surgery, previous studies in other patient populations have demonstrated that the two instruments do not always correlate.23,24 Employing both instruments thus permits a more comprehensive analysis of HR-QoL outcomes in our patient population. Furthermore, unlike the SF-36, EQ-5D data can be used to calculate quality-adjusted life years, which are useful in evaluating the economic impact of medical interventions.8 Our findings are different from those reported by Coughlin and colleagues, who pooled SF-36 data from 16 studies to examine pre- and postoperative HR-QoL outcomes of OAR vs EVAR up to 1 year.25 Those authors
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a Study name Outcome
Sample size
Std diff in means and 95% CI
Std diff in means p-Value EVAR OAR DREAM EVAR 1 Lottman Soulez
EQ-5D EQ-5D EQ-5D EQ-5D
-0.079 -0.260 -0.061 -0.577 -0.226
0.645 0.005 0.828 0.086 0.003
73 238 52 20
65 245 17 17 -1.00 -0.50
0.00
0.50
1.00
Favors EVAR Favors OAR
b
Study name Outcome
Sample size
Std diff in means and 95% CI
Std diff in means p-Value EVAR OAR DREAM Soulez
EQ-5D EQ-5D
-0.485 -0.361 -0.459
0.005 0.283 0.003
74 19
65 17 -1.00 -0.50
0.00
0.50
1.00
Favors EVAR Favors OAR
c
Study name Outcome
Sample size
Std diff in means and 95% CI
Std diff in means p-Value EVAR OAR DREAM EVAR-1 OVER Soulez
EQ-5D EQ-5D EQ-5D EQ-5D
-0.493 -0.083 -0.121 -0.739 -0.212
0.004 0.217 0.078 0.035 0.022
73 476 429 19
68 414 421 16 -1.00 -0.50
0.00
0.50
1.00
Favors EVAR Favors OAR
d
Study name Outcome
Sample size
Std diff in means and 95% CI
Std diff in means p-Value EVAR OAR EVAR-1 OVER Soulez
EQ-5D EQ-5D EQ-5D
-0.041 0.057 -0.401 -0.001
0.572 0.452 0.322 0.985
398 350 12
371 348 13 -1.00 -0.50
0.00
0.50
1.00
Favors EVAR Favors OAR Fig 2. Meta-analysis of the standard difference in means between open aneurysm repair (OAR) and endovascular repair (EVAR) EuroQol-5D (EQ-5D) scores at 3 (a), 6 (b), 12 (c), and 24 months (d). Negative result favors EVAR. CI, Confidence interval; DREAM, Dutch Randomised Endovascular Aneurysm Management Study; EVAR 1, Endovascular Aneurysm Repair Study; std diff, standard difference.
reported an advantage for EVAR over OAR in the SF-36 domains of vitality and physical role functioning at 3 months. No significant differences, however, were found between SF-36 domains for EVAR and OAR after 3 months. Conversely, we report an advantage for EVAR over OAR in the SF-36 general health domain at 3, 6, and 12 months postoperatively. We report a similar
advantage for EVAR in physical functioning at 6 months and social functioning at 12 months. Coughlin and colleagues did not report on EQ-5D outcomes, whereas we demonstrated an advantage for EVAR when considering EQ-5D outcomes for up to 12 months. The differences between our findings and those reported by Coughlin and colleagues might be explained by our different study
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Fig 3. Funnel plot for EuroQol-5D (EQ-5D) studies at 12 months. Absence of studies in the right lower area under the funnel suggests publication bias against studies favoring open aneurysm repair (OAR). std diff, Standard difference.
inclusion criteria. As mentioned earlier, we chose to limit our analysis to randomized controlled trials that specifically compared HR-QoL outcomes between OAR and EVAR, whereas Coughlin’s study also included nonrandomized cohort studies and studies including an observational arm. Moreover, Coughlin and colleagues did not include in their meta-analysis a randomized controlled trial by Soulez’ group that reported an advantage in certain SF-36 domains among EVAR patients.11 The short-term HR-QoL advantage for EVAR over OAR could be explained by the avoided laparotomy and longer hospital stay that are inherent with OAR. One would expect the EVAR patient who is discharged home on the first postoperative day with small groin incisions to report a higher HR-QoL satisfaction than the patient undergoing OAR. Our findings suggest, however, that this advantage lasts up to 1 year, which suggests that the differences go beyond the immediate wound healing issues to include a longer recovery period needed for patients who undergo major operations. While none of the studies included in our analysis followed patients beyond 2 years (Table II), we have shown that, beyond 1 year, the differences in QoL are no longer present. Reasons for this might include issues unique to EVAR such as endoleak and the need for long term surveillance among EVAR patients. Furthermore, long-term HR-QoL measures can be diluted by other nonaneurysm related issues affecting the elderly patients in this population. While we have demonstrated an advantage in HR-QoL outcomes for EVAR over OAR for up to 12 months, the extent to which either the SF-36 or the EQ-5D questionnaires are responsive to changes among OAR and EVAR patients is unclear. Because of the general nature of those questionnaires, they might not be able to detect small
changes in HR-QoL outcomes unique to patients with aortic disease before or after undergoing open or endovascular interventions. This may explain why we found no difference between SF-36 summary scores but a significant difference between some of the SF-36 domains. It also highlights the need for a disease-specific HR-QoL instrument developed specifically for this patient population, similar to previously developed instruments such as the Claudication Scale (CLAU-S)26 or the Edinburgh Claudication Questionnaire (ECQ)27 for claudicants. The clinical relevance of our findings lies in its qualitative rather than quantitative clinical implications: that there is a significant postoperative quality-of-life advantage favoring EVAR in EQ-5D and in several SF-36 domains, but that this advantage is lost at 1 year of follow-up. Our study is not without limitations. We are limited by the small number of trials that were included in the analysis. We chose to restrict our analysis to randomizedcontrolled trials that directly compared HR-QoL outcomes between OAR and EVAR. We excluded trials of EVAR in small aneurysms (such as the Comparison of Surveillance vs Aortic Endografting for Small Aneurysm Repair [CAESAR] trial28) or trials that compared EVAR with surveillance (such as the EVAR-2 trial29) because the study design and study inclusion criteria are different from the trials directly comparing OAR and EVAR. We have also identified a possible publication bias against HR-QoL trials favoring OAR vs EVAR. However, a search of the online clinical trial registry, clinicaltrials.gov, did not suggest that any registered trials comparing HR-QoL outcomes between EVAR or OAR were not published, which suggests that our findings can be explained by the small number of studies included in our analysis rather than a genuine publication bias. Given the proven safety and effectiveness
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surgical team.30 However, this would not have been feasible or practical in trials comparing open and endovascular abdominal aortic aneurysm repair. Blinded patients are less likely to have biased psychological or physical responses to intervention or to seek additional adjunct interventions.31 Moreover, blinded trial investigators are less likely to transfer their views to patients or to administer extra interventions.31 It is unclear, however, what effect, if any, this lack of blinding had on the estimation of the true difference in HR-QoL outcomes between the two treatment modalities. Finally, the generalizability of our results will be impacted by the advent of newer EVAR stents and deployment techniques and the increasing uptake of EVAR among vascular surgeons. This will likely affect the rate of intra- and postoperative complications and, ultimately, the patient HR-QoL outcomes. This limitation, however, is inherent to all studies that analyze evolving technologies. These limitations notwithstanding, our study represents a contemporary comprehensive meta-analysis of HR-QoL outcomes in patients undergoing abdominal aneurysm interventions. Because no universally accepted HR-QoL instrument was used in these trials, our validated conversion methods allowed for direct comparison of results from different trials. Our study also highlights the current diversity of approaches to utility measurement among vascular researchers, as well as the usefulness of having a standardized instrument such as the EQ-5D for conducting economic analyses on today’s plethora of emerging technologies. CONCLUSIONS
Fig 4. Cochrane risk of bias summary: Review authors’ judgements about each risk of bias item for each included study. Green circle, low risk of bias; red circle, high risk of bias; empty square, unclear risk of bias. DREAM, Dutch Randomised Endovascular Aneurysm Management Study; EVAR 1, Endovascular Aneurysm Repair Study; OVER, Open Versus Endovascular Repair Study.
EVAR is associated with better HR-QoL for up to 1 year postoperatively, but the advantage is not seen at 2 years. More studies are required, however, to examine any long-term HR-QoL advantages for either intervention, especially in light of the need for continued surveillance of EVAR patients. The authors would like to thank Dr Paul Bain for his help with searching the literature and Dr George Tomlinson for his guidance with meta-analysis methodology. AUTHOR CONTRIBUTIONS
of endovascular abdominal aortic interventions and the current lack of clinical equipoise regarding their use among vascular surgeons, it is unlikely that future trials will be conducted to compare the effectiveness of open vs endovascular abdominal aortic aneurysm repair, which could allow for more HR-QoL data to be gathered and analyzed. As such, we are limited by the available data from previously conducted trials. We have identified a high risk of performance and detection bias, both of which stem from a lack of blinding, in all of the included studies. This remains a significant challenge in surgical trials and may be mitigated by the introduction of sham operations or the use of a second
Conception and design: AK, LN Analysis and interpretation: AK, AS, GR-N, LN Data collection: AK, AS Writing the article: AK, AS, GR-N, LN Critical revision of the article: AK, AS, GR-N, LN Final approval of the article: AK, AS, GR-N, LN Statistical analysis: AK Obtained funding: Not applicable Overall responsibility: LN REFERENCES 1. Bengtsson H, Sonesson B, Bergqvist D. Incidence and prevalence of abdominal aortic aneurysms, estimated by necropsy studies and population screening by ultrasound. Ann NY Acad Sci 1996;800:1-24.
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Submitted Feb 7, 2015; accepted May 14, 2015.