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Impact of Endovascular Repair on the Outcomes of Octogenarians with Ruptured Abdominal Aortic Aneurysms: A Nationwide Japanese Study
Eur J Vasc Endovasc Surg (xxxx) xxx, xxx
Impact of Endovascular Repair on the Outcomes of Octogenarians with Ruptured Abdominal Aortic Aneurysms: A Nationwide Japanese Study Tetsuo Yamaguchi a,b,*, Michikazu Nakai c, Yoko Sumita c, Kunihiro Nishimura c, Toshiyuki Nagai d, Toshihisa Anzai d, Yasushi Sakata e, Hitoshi Ogino f a
Department of Cardiovascular Centre, Toranomon Hospital, Tokyo, Japan Department of Cardiology, Japanese Red Cross Musashino Hospital, Tokyo, Japan c National Cerebral and Cardiovascular Centre, Osaka, Japan d Department of Cardiovascular Medicine, Faculty of Medicine and Graduate School of Medicine Hokkaido University, Sapporo, Japan e Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Osaka, Japan f Department of Cardiovascular Surgery, Tokyo Medical University, Tokyo, Japan b
WHAT THIS PAPER ADDS This nationwide claim based data analysis demonstrated that open surgical repair was less probably to be performed for elderly patients (aged 80 y) with ruptured abdominal aortic aneurysm (rAAA), but endovascular repair (EVAR) was performed similarly. Although old age was an independent predictor of in hospital death for the overall cohort, a small subgroup of elderly patients currently selected for EVAR enjoyed favourable outcomes. Although EVAR for rAAA is not recommended as a first line treatment in current Japanese guidelines, its further implementation, especially in elderly patients with suitable anatomy, may be justified.
Objective: This study aimed to clarify the impact of endovascular aneurysm repair (EVAR) on clinical outcomes in Japanese patients of advanced age with ruptured abdominal aortic aneurysm (rAAA). Methods: This was a national registry based retrospective comparative study, using data from the Japanese Registry Of All cardiac and vascular Diseases-Diagnostic Procedure Combination (JROAD-DPC), a nationwide claim based database from more than 600 hospitals. Patients admitted with rAAA between April 1, 2012, and March 31, 2015 were included in the study. Patient characteristics, management, and outcomes were compared between the elderly (aged 80 y) and the less old. The primary endpoint was in hospital mortality; the secondary endpoint was the functional status at discharge. Results: Of 3 969 eligible patients, 49.9% were categorised as elderly. Elderly patients had a higher prevalence of female gender (41.8% vs. 17.0%, p < .001) and disturbance of consciousness on admission (28.6% vs. 20.7%, p < .001). They were less likely to undergo open surgical repair (31.6% vs. 56.7%, p < .001), although EVAR was performed similarly in both groups (13.7% vs. 14.8%, p ¼ .33). The unadjusted mortality rate (61.8% vs. 37.6%, p < .001) and mean Barthel index at discharge (73.0 vs. 91.8, p < .001) were statistically significantly worse in the elderly. Multilevel mixed effect logistic regression analyses showed that old age was detected as an independent predictor of in hospital death (odds ratio 2.75; 95% confidence interval, 2.39e3.17; p < .001). However, for patients who received EVAR, old age was not statistically significant (odds ratio 1.13; 95% confidence interval, 0.77e1.66; p ¼ .53). Conclusion: Elderly patients with rAAA were less likely to be offered open surgical repair, and the mortality among those who received surgery was high. However, for the small subgroup of elderly patients currently selected for EVAR there was a favourable outcome. The further implementation of EVAR for rAAA in Japan, especially for elderly patients with suitable anatomy, may be justified. Keywords: Elderly patients, Endovascular aneurysm repair, JROAD, Ruptured abdominal aortic aneurysms Article history: Received 28 March 2019, Accepted 14 July 2019, Available online XXX Ó 2019 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.
INTRODUCTION * Corresponding author. Department of Cardiovascular Centre, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo 105e8470, Japan. E-mail address: [email protected] (Tetsuo Yamaguchi). 1078-5884/Ó 2019 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved. https://doi.org/10.1016/j.ejvs.2019.07.016
A ruptured abdominal aortic aneurysm (rAAA) still carries a high mortality.1e3 Previous studies4e6 have reported that only 25e29% of elderly patients (aged 80 years) were offered open surgical repair or endovascular repair (EVAR) for rAAA. Indeed, advanced age is considered a major risk
Please cite this article as: Yamaguchi T et al., Impact of Endovascular Repair on the Outcomes of Octogenarians with Ruptured Abdominal Aortic Aneurysms: A Nationwide Japanese Study, European Journal of Vascular and Endovascular Surgery, https://doi.org/10.1016/j.ejvs.2019.07.016
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factor for early post-operative death.7,8 However, EVAR is potentially suitable and beneficial for elderly patients because of its low invasiveness. Indeed, lower perioperative morbidity rates and similar in hospital mortality rates with EVAR rather than open surgery for rAAA have been shown in previous studies.9e11 EVAR for rAAA and suitable anatomy is recommended as the first line option in the European Society for Vascular Surgery (ESVS) guidelines.12 According to Japanese guidelines,13 EVAR is not recommended for emergency surgery (including rupture) and may be considered only in cases of rupture with stable haemodynamics. Furthermore, few data exist concerning the impact of EVAR on the clinical outcomes in Japanese patients of advanced age with rAAA. The present study compared patient characteristics, management (EVAR, open surgical repair, or conservative treatment) and the outcomes of elderly (aged 80 y) and younger patients with rAAA using the Japanese Registry Of All cardiac and vascular Diseases-Diagnostic Procedure Combination (JROAD-DPC) database. The primary endpoint was in hospital mortality; the secondary endpoint was the functional status at discharge. METHODS Database explanation The JROAD-DPC is a nationwide claim based database based on data from the Japanese DPC/Per Diem Payment System in hospitals participating in the JROAD survey.14 The JROAD database has been described in detail previously.15e17 In brief, all teaching hospitals with cardiovascular beds participate in the JROAD. Hospital doctors must record all admission and discharge data for each patient and are obliged to guarantee their accuracy. This study analysed the JROAD-DPC data from 610 hospitals in 2012, 637 hospitals in 2013, and 742 hospitals in 2014 from all regions in Japan between April 1, 2012, and March 31, 2015.
Tetsuo Yamaguchi et al.
procedures including EVAR, during this period were excluded, because patients transferred to such hospitals might be dead on arrival or unable to undergo surgical treatment. In addition, patients admitted to non-teaching hospitals were excluded to standardise the quality of treatment and data because response rates of teaching hospitals in the JROAD survey were 100%.15 Patients who underwent both EVAR and open surgery were excluded because it could not be determined whether these were intra-operative conversions or planned staged procedures. The cut off age (80 years) was determined by referencing previous studies4e6 and ESVS guidelines.12 The following clinical data were extracted from the database: patient background characteristics; comorbidities; hospital information including bed number, number of aortic procedures per year, and number of cardiovascular surgeons; treatments including operations, drugs, and additional treatments, such as transfusions and vasopressors; in hospital death; consciousness level both on admission and discharge according to the Japan Coma Scale;18,19 and Barthel index (BI) at discharge. Disturbance of consciousness (DOC) was defined as a Japan Coma Scale score of 100e300, as described in a previous report.18 A BI 75 was considered to be a favourable functional status at discharge, according to a previous report.20 Emergency operation was defined as open surgery and/or EVAR performed within one day of admission. Ethical consideration This research plan was designed by the authors and approved by the Institutional Review Board of the Japanese Red Cross Musashino Hospital (approval number: 367). The requirement for informed consent was waived because of the anonymised data. All participants were notified through homepages or posters at each hospital and were told that they were free to opt out of participation at any time. The study complied with the Declaration of Helsinki and Japanese Ethical Guideline for Medical and Health Research involving Human Subjects.
Study participants Patients hospitalised for ruptured aortic aneurysms were identified primarily based on the International Classification of Diseases (ICD)-10 diagnosis codes (ruptured thoracic aortic aneurysm: I711; ruptured abdominal aortic aneurysm: I713; and ruptured thoracic-abdominal aortic aneurysm: I715). In the JROAD-DPC database, aortic dissections and non-ruptured aortic aneurysms are clearly distinguished from ruptured aortic aneurysms. Diagnosis and comorbidities were primarily defined based on the ICD-10 codes, but they were also checked by the physicians to examine whether they matched the treatments performed for each patient and to determine whether these were compatible with the code data.14 Additionally, the diagnosis written in Japanese in the DPC database was used to increase the accuracy of the diagnosis.17 Patients admitted to hospitals that did not perform any cardiovascular
Statistical analyses Data were expressed as the mean and standard deviation for normally distributed variables and as median with the interquartile range for non-normally distributed data. Continuous variables were compared by Student’s t test or the ManneWhitney U test as appropriate. Categorical data were expressed as numbers and percentages and compared by the chi-square test or Fisher’s exact test. Multilevel mixed effect logistic regression analyses using institutional codes as random intercepts were performed to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) for the in hospital death of the elderly patient group compared with the younger patients, adjusted for gender, history of heart failure, chronic obstructive pulmonary disease, diabetes mellitus, cerebrovascular disease, renal failure on admission, DOC on admission, the need for vasopressor
Please cite this article as: Yamaguchi T et al., Impact of Endovascular Repair on the Outcomes of Octogenarians with Ruptured Abdominal Aortic Aneurysms: A Nationwide Japanese Study, European Journal of Vascular and Endovascular Surgery, https://doi.org/10.1016/j.ejvs.2019.07.016
EVAR for Elderly Japanese rAAA Patients
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administration in the emergency department, hospital bed number, and number of cardiovascular surgeons. These variables were selected according to their clinical importance based on previous studies.8,21e25 Discrimination of the selected variables was confirmed by a receiver operator characteristics (ROC) analysis. Furthermore, as sensitivity analyses, additional logistic regression analyses were performed using another cut off age made by the ROC analysis for in hospital death. Statistical analyses were performed by a physician (Yamaguchi T) and a statistician (Nakai M) using the Stata software program, ver. 14.2 (StataCorp, College Station, TX, USA). A two sided p value < .05 was considered statistically significant.
higher prevalence of DOC on admission than younger patients (28.6% vs. 20.7%, p < .001). Elderly patients were transferred to hospitals with fewer cardiovascular surgeons and annual aortic procedures than younger patients. The baseline characteristics of the patients stratified by age group and treatments performed are shown in Table S1. Overall, patients who were managed medically were older with a lower body mass index and markedly higher prevalence of DOC on arrival, and they were transferred to hospitals with fewer cardiovascular surgeons and annual aortic procedures in both groups.
RESULTS
Fig. 2 shows the key outcomes of this study, and Table 2 shows the treatments and outcomes comparing the elderly and younger patients. A small number of patients (elderly: 2.5% [49/1 982], younger: 3.5% [69/1 987]) received delayed (more than one day after arrival) operative treatment. Elderly patients were less likely to undergo emergency operation (42.8% vs. 68.0%, p < .001) and open surgical repair (31.6% vs. 56.7%, p < .001) than younger patients. However, EVAR was performed at a similar rate in both groups (13.7% vs. 14.8%, p ¼ .33), and the ratio of EVAR to open surgery was much higher in the elderly patients than in the younger patients (43.5% vs. 26.1%, p < .001). The unadjusted in hospital mortality rate of elderly patients was statistically significantly worse than that in the younger patients (61.8% vs. 37.6%, p < .001).
Patient characteristics A total of 8 032 patients (aged 20 years) admitted with a primary diagnosis of ruptured aortic aneurysm from April 1, 2012, to March 31, 2015, were extracted from the database. The patient selection flowchart is shown in Fig. 1. A total of 7 086 patients from 564 hospitals were identified and 3 991 had rAAA. After excluding non-eligible patients, 1 982 patients (49.9%) were elderly (aged 80 years). The baseline characteristics of the patients stratified by age group are shown in Table 1. Female patients were dominant in the elderly group compared with the young group (41.8% vs. 17.0%, p < .001). The elderly showed a statistically significantly lower body mass index (21.2 vs. 23.3, p < .001) and a
Clinical outcomes
Patients with ruptured aortic aneurysms (n=8 302)
Patients asmitted to hospitals not performing any cardiovascular operations (n=1 026)
Patients admitted to non-teaching hospitals (n=190)
Patients from 564 hospitals (n = 7 086) Thoracic aneurysm (n=2 700)
Thoraco-abdominal aneurysm (n=395)
Abdominal aneurysm (n=3 991) Missing data for age (n=2)
Patients who underwent both EVAR and open surgery (n=20)
Study population (n=3 969)
Octogenarians (n=1 982)
Younger group (n=1 987)
Figure 1. Study flow chart. EVAR ¼ endovascular aneurysm repair.
Please cite this article as: Yamaguchi T et al., Impact of Endovascular Repair on the Outcomes of Octogenarians with Ruptured Abdominal Aortic Aneurysms: A Nationwide Japanese Study, European Journal of Vascular and Endovascular Surgery, https://doi.org/10.1016/j.ejvs.2019.07.016
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Tetsuo Yamaguchi et al.
Table 1. Baseline characteristics of 3 969 Japanese patients with ruptured abdominal aortic aneurysm, stratified by age group Parameter
Octogenarians Younger (n [ 1982) patients (n [ 1987)
Age e y 86.2 4.3 Female gender 829 (41.8) Body mass index e kg/m2 21.2 4.6 Medical history Heart failure 181 (9.1) Myocardial infarction 55 (2.8) Cerebrovascular disease 145 (7.3) COPD 69 (3.5) Diabetes mellitus 133 (6.7) Renal failure on 156 (7.9) admission Need for additional treatment Transfusion 1080 (54.5) Vasopressor 982 (49.5) Disturbance of 567 (28.6) consciousness on arrival Institutional parameters Number of beds (missing n ¼ 1) 20e100 beds 20 (1.0) 100e200 beds 39 (2.0) 200e300 beds 114 (5.8) 300e450 beds 439 (22.1) 450e750 beds 993 (50.1) > 750 beds 377 (19.0) Number of cardiovascular 5.0 (3.0e7.0) surgeons Number of certified 6.0 (4.0e10.0) cardiologists Annual aortic procedures 116.2 89.2 Annual endovascular 34.1 33.3 aneurysm repair Data are medians defined COPD ¼
p
69.7 7.3 337 (17.0) 23.3 4.7
<.001 <.001 <.001
227 (11.4) 63 (3.2) 133 (6.7) 69 (3.5) 202 (10.2) 167 (8.4)
.017 .46 .44 .99 <.001 .54
1492 (75.1) 1373 (69.1) 412 (20.7)
<.001 <.001 <.001
.88 18 (0.9) 44 (2.2) 125 (6.3) 417 (21.0) 991 (49.9) 391 (19.7) 5.0 (3.0e8.0) <.001 7.0 (4.0e11.0) .002 124.3 89.7 37.6 34.0
.005 <.001
expressed as numbers (%), means standard deviations, or (interquartile range). A disturbance of consciousness was as a Japan Coma Scale of from 100 to 300. chronic obstructive pulmonary disease.
Similarly, patients who were discharged with a favourable functional status (BI 75) were statistically significantly less frequent among elderly patients than among younger patients (55.3% vs. 85.0%, p < .001). Table S2 shows the outcomes by each treatment comparing the elderly and the young. Unadjusted mortality was higher in the elderly patients for all types of management than in younger patients. The mortality rate with conservative therapy in this database was 89.9% in the elderly patients and 82.2% in the young patients. Table 3 shows the results of multilevel mixed effect logistic regression analyses for in hospital death. In the multivariable analyses, the area under the curve (AUC) of the selected variables in the ROC curve was 0.85 (95% CI 0.84e0.86). Old age (cut off: 80 years) was detected as an independent predictor of in hospital death in the overall cohort after adjusting for covariates (OR 2.43; 95% CI 2.06e 2.87; p < .001). This trend was similar when analyses were
performed for the patients receiving open surgery and medical management. However, only for patients who underwent EVAR, was old age not statistically significant (OR 1.13; 95% CI 0.77e1.66; p ¼ .53). Similar results were confirmed when analyses were performed at another cut off age (76 years) determined by the ROC analysis (Table 3). DISCUSSION This is the largest population based study to compare the characteristics, management, and outcomes of elderly Japanese patients with rAAA with those of younger patients. The main finding was that although elderly patients had a worse overall mortality rate and functional status at discharge than younger patients, those who received EVAR showed a comparable outcome to younger patients. Previous studies have shown a low rate of emergency surgery (25e29%) for rAAA in elderly patients.4e6 A similar trend was noted in the present study, where statistically significantly fewer elderly patients with rAAA underwent emergency operations than younger patients (42.8% vs. 68.0%, p < .001). This may be because of their older age and more severe clinical presentation, such as a higher rate of DOC on arrival, than in younger patients. Older age can be related to delayed or missed diagnosis of aortic aneurysms, which can result in a more severe clinical presentation. Previous studies have shown that although elderly patients have a significantly higher risk of post-operative death compared with younger patients, open surgical repair has been life saving in 33% of elderly patients,26 and the mortality rate of 59% in the pooled analysis of 36 studies was deemed acceptable.27 In the present study, the mortality rate of elderly patients receiving open surgery was also acceptable at 28.8%, which was similar to the 30 day mortality of 26.7% from a tertiary referral centre.28 In addition, the intermediate survival rates (at one, two and three years after surgery) of elderly patients with rAAA are also reported to be acceptable (82%, 76%, and 69%, respectively).29 For these reasons, the ESVS guideline recommends that advanced age alone should not prevent surgery for rAAA. Because elderly patients have more comorbidities than younger patients, EVAR may be more beneficial for the former population because of its low invasiveness. In the present study, the ratio of EVAR to open surgery was much higher in the elderly patients than in the younger ones (43.5% vs. 26.1%, p < .001). Furthermore, a multivariable analysis showed that elderly patients receiving EVAR enjoyed comparable outcomes to younger patients. Similar results were reported in a previous study,30 showing that the peri-operative mortality in elderly patients was higher than that in younger patients, although not to a statistically significant degree when only EVAR was performed. Previous studies have shown that, with the advancements in endografts, nearly 80% of patients can be treated by EVAR,31 and three quarters of patients with rAAA can be considered for EVAR, regardless of their haemodynamic
Please cite this article as: Yamaguchi T et al., Impact of Endovascular Repair on the Outcomes of Octogenarians with Ruptured Abdominal Aortic Aneurysms: A Nationwide Japanese Study, European Journal of Vascular and Endovascular Surgery, https://doi.org/10.1016/j.ejvs.2019.07.016
Proportion of favourable in hospital outcome – %
EVAR for Elderly Japanese rAAA Patients
5
p <.001
100 80
p < .001
31.6
20 0
61.8
56.7
60 40
85.0
p < .001
55.3 37.6
p = .33 13.7 14.8
Open surgical repair
Endovascular repair Octogenarians
In-hospital death
Favourable functional status at discharge
Younger
Figure 2. A comparison of key in hospital outcomes between octogenarians and younger patients. A favourable functional status at discharge was defined as a Barthel index 75. Results from a population based analysis of 3 969 Japanese patients with ruptured abdominal aortic aneurysm.
status.32 For these reasons, EVAR for rAAA, especially in elderly patients, can be performed widely in Japan if the anatomy is suitable. There are several limitations with the present study. First, because this study was a retrospective analysis of claim based data, there may be risks of systemic or nonsystemic coding errors or insufficient data collection. However, the validity of the DPC database is generally high, especially for primary diagnoses and procedure records.33 In addition, because these coding errors are likely to affect all comparison groups equally, comparative studies may be useful. Although attempts were made to adjust for confounders as much as possible using clinically important predictors and the discrimination power of the selected variables was relatively high (AUC: 0.85), unadjusted confounding factors may have existed. Second, the DPC database does not include detailed data on the aortic anatomy, such as aneurysm neck length, Fitzgerald classification, type of stent graft implanted, duration from onset to arrival, or blood pressure at arrival, blood pressure management, and pre-operative volume resuscitation.
Table 2. Treatments and clinical outcomes of 3969 Japanese patients with ruptured abdominal aortic aneurysm, stratified by age group Parameter Management Medical management Emergency repair < 24 h Delayed repair Open surgical repair Endovascular repair Endovascular repair/open surgical repair Clinical outcomes In hospital death Barthel index at discharge Favourable functional status at discharge Other outcomes Length of hospitalisation e d
Octogenarians (n [ 1982)
Younger patients (n [ 1987)
p
1084 (54.7) 849 (42.8) 49 (2.5) 626 (31.6) 272 (13.7) 272/626 (43.4)
567 (28.5) 1351 (68.0) 69 (3.5) 1126 (56.7) 294 (14.8) 294/1126 (26.1)
<.001 <.001 .064 <.001 .33 <.001
1225 (61.8) 73.0 (30.5) 419/757 (55.4)
748 (37.6) 91.8 (19.6) 1053/1239 (85.0)
<.001 <.001 <.001
24 (16e37)
22 (15e34)
.011
Data are expressed as numbers (%), or medians (interquartile range). Emergency operation was defined as open surgery and/or endovascular aneurysm repair performed within one day of admission. A favourable functional status was defined as a Barthel index at discharge 75.
Table 3. Multivariable logistic regression analyses for risk of in hospital death stratified by management approach Age groups
Overall in hospital mortality* OR
Younger Octogenarians Elderly (cut off: 76)
95% CI
1 (Reference) 2.43 2.06e2.87 2.40 2.03e2.85
In hospital mortality after open surgical repair* p
OR
<.001 <.001
1 (Reference) 1.88 1.45e2.44 1.93 1.49e2.49
95% CI
In hospital mortality after endovascular repair*
p
OR
<.001 <.001
1 (Reference) 1.13 0.77e1.66 1.26 0.84e1.89
95% CI
In hospital mortality after medical treatment*
p
OR
.53 .26
1 (Reference) 2.53 1.71e3.72 2.72 1.79e4.13
95% CI
p <.001 <.001
Results from a population based analysis of 3969 Japanese patients with ruptured abdominal aortic aneurysm. OR ¼ odds ratio; CI ¼ confidence interval. * Adjusted for gender, history of heart failure, chronic obstructive pulmonary disease, diabetes mellitus, cerebrovascular disease, renal failure on admission, disturbance of consciousness on admission, the need for vasopressor administration in the emergency department, hospital bed number, and number of cardiovascular surgeons.
Please cite this article as: Yamaguchi T et al., Impact of Endovascular Repair on the Outcomes of Octogenarians with Ruptured Abdominal Aortic Aneurysms: A Nationwide Japanese Study, European Journal of Vascular and Endovascular Surgery, https://doi.org/10.1016/j.ejvs.2019.07.016
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However, renal failure at admission, DOC at admission, and the need for vasopressor administration in the emergency department in the multivariable analyses were used as surrogates for unstable haemodynamics and a low blood pressure on admission. Third, it was not possible to determine indications for treatment, so the possibility of selection bias cannot be ruled out. However, claim based databases have strengths of including treatments performed by large numbers of healthcare providers and medical specialties, no selection bias by physicians, and high external validity, as no reimbursement is received without the submission of data to the funder.34 Fourth, the non-surgery rate was very high in this study. Because some of the hospitals participating in this study are not the large operating centres, patients managed medically may include those who arrived at the hospital almost dead, and those who could not undergo surgery because of severe complications. A previous meta-analysis35 showed that the non-surgery rate for rAAA was nearly 40%, which was similar to that noted in the present study. Considering publication bias, the non-surgery rate of non-referral centres may be higher than 40%. Therefore, it is considered that this high non-surgery rate reflects the real world situation in Japan. The mortality rates of patients who were managed medically in the same meta-analysis35 range between 75% and 90%, which was also similar to the present results. Finally, it was only possible to evaluate the in hospital outcomes and not the longer term outcomes. CONCLUSIONS The present analysis of a nationwide administrative database demonstrated that elderly patients with rAAA had worse in hospital mortality and functional status at discharge than young patients. Elderly patients with rAAA were less likely to be offered open surgical repair, and the mortality among those who received surgery was high. However, the small subgroup of elderly patients currently selected for EVAR showed a favourable outcome. Further implementation of EVAR for rAAA in Japan, especially for elderly patients with suitable anatomy, may be justified. CONFLICT OF INTEREST None. FUNDING None. APPENDIX A. SUPPLEMENTARY DATA Supplementary data to this article can be found online at https://doi.org/10.1016/j.ejvs.2019.07.016. REFERENCES 1 Hoornweg LL, Storm-Versloot MN, Ubbink DT, Koelemay MJ, Legemate DA, Balm R. Meta analysis on mortality of ruptured abdominal aortic aneurysms. Eur J Vasc Endovasc Surg 2008;35: 558e70.
Tetsuo Yamaguchi et al. 2 Sidloff D, Stather P, Dattani N, Bown M, Thompson J, Sayers R, et al. Aneurysm global epidemiology study: public health measures can further reduce abdominal aortic aneurysm mortality. Circulation 2014;129:747e53. 3 Edwards ST, Schermerhorn ML, O’Malley AJ, Bensley RP, Hurks R, Cotterill P, et al. Comparative effectiveness of endovascular versus open repair of ruptured abdominal aortic aneurysm in the Medicare population. J Vasc Surg 2014;59:575e82. 4 Heikkinen M, Salenius JP, Auvinen O. Ruptured abdominal aortic aneurysm in a well- defined geographic area. J Vasc Surg 2002;36: 291e6. 5 Bradbury AW, Makhdoomi KR, Adam DJ. Twelve-year experience of the management of ruptured abdominal aortic aneurysm. Br J Surg 1997;84:1705e7. 6 Anjum A, von Allmen R, Greenhalgh R, Powell JT. Explaining the decrease in mortality from abdominal aortic aneurysm rupture. Br J Surg 2012;99:637e45. 7 Samy AK, Murray G, MacBain G. Glasgow aneurysm score. Cardiovasc Surg 1994;2:41e4. 8 Hardman DT, Fisher CM, Patel MI, Neale M, Chambers J, Lane R, et al. Ruptured abdominal aortic aneurysms: who should be offered surgery? J Vasc Surg 1996;23:123e9. 9 IMPROVE Trial Investigators, Powell JT, Sweeting MJ, Thompson MM, Ashleigh R, Bell R, et al. Endovascular or open repair strategy for ruptured abdominal aortic aneurysm: 30 day outcomes from IMPROVE randomised trial. BMJ 2014;348:f7661. 10 Antoniou GA, Georgiadis GS, Antoniou SA, Pavlidis P, Maras D, Sfyroeras GS, et al. Endovascular repair for ruptured abdominal aortic aneurysm confers an early survival benefit over open repair. J Vasc Surg 2013;58:1091e105. 11 von Meijenfeldt GC, Ultee KH, Eefting D, Hoeks SE, ten Raa S, Rouwet EV, et al. Differences in mortality, risk factors, and complications after open and endovascular repair of ruptured abdominal aortic aneurysms. Eur J Vasc Endovasc Surg 2014;47:479e86. 12 Wanhainen A, Verzini F, Van Herzeele I, Allaire E, Bown M, Cohnert T, et al. European society for vascular surgery (ESVS) 2019 clinical practice guidelines on the management of abdominal aorto-iliac artery aneurysms. Eur J Vasc Endovasc Surg 2019;57:8e93. 13 JCS Joint Working Group. Guidelines for diagnosis and treatment of aortic aneurysm and aortic dissection (JCS 2011): digest version. Circ J 2013;77:789e828. 14 Yasuda S, Nakao K, Nishimura K, Miyamoto Y, Sumita Y, Shishido T, et al. The current status of cardiovascular medicine in Japan - analysis of a large number of health records from a nationwide claimbased database, JROAD-DPC. Circ J 2016;80:2327e35. 15 Yasuda S, Miyamoto Y, Ogawa H. Current status of cardiovascular medicine in the aging society of Japan. Circulation 2018;138: 965e7. 16 Yamaguchi T, Nakai M, Sumita Y, Nishimura K, Miyamoto T, Sakata Y, et al. The impact of institutional case volume on the prognosis of ruptured aortic aneurysms: a Japanese nationwide study. Interact Cardiovasc Thorac Surg 2019;29:109e16. 17 Yamaguchi T, Nakai M, Sumita Y, Nishimura K, Tazaki J, Kyuragi R, et al. Endovascular repair versus surgical repair for Japanese patients with ruptured thoracic and abdominal aortic aneurysms: a nationwide study performed in Japan. Eur J Vasc Endovasc Surg 2019;57:779e86. 18 Iihara K, Nishimura K, Kada A, Nakagawara J, Ogasawara K, Ono J, et al. Effects of comprehensive stroke care capabilities on in-hospital mortality of patients with ischemic and hemorrhagic stroke: J-ASPECT study. PLoS One 2014;9:e96819. 19 Shigematsu K, Nakano H, Watanabe Y. The eye response test alone is sufficient to predict stroke outcome–reintroduction of Japan Coma Scale: a cohort study. BMJ Open 2013;3:e002736. 20 Uyttenboogaart M, Stewart RE, Vroomen PC, De Keyser J, Luijckx GJ. Optimizing cutoff scores for the Barthel Index and the modified Rankin Scale for defining outcome in acute stroke trials. Stroke 2005;36:1984e7.
Please cite this article as: Yamaguchi T et al., Impact of Endovascular Repair on the Outcomes of Octogenarians with Ruptured Abdominal Aortic Aneurysms: A Nationwide Japanese Study, European Journal of Vascular and Endovascular Surgery, https://doi.org/10.1016/j.ejvs.2019.07.016
EVAR for Elderly Japanese rAAA Patients 21 Korhonen SJ, Ylönen K, Biancari F, Heikkinen M, Salenius JP, Lepantalo M. Glasgow Aneurysm Score as a predictor of immediate outcome after surgery for ruptured abdominal aortic aneurysm. Br J Surg 2004;91:1449e52. 22 Robinson WP, Schanzer A, Li Y, Goodney PP, Nolan BW, Eslami MH, et al. Derivation and validation of a practical risk score for prediction of mortality after open repair of ruptured abdominal aortic aneurysms in a U.S. regional cohort and comparison to existing scoring systems. J Vasc Surg 2013;57:354e61. 23 Wise E, Hocking K, Brophy C. Prediction of in-hospital mortality after ruptured abdominal aortic aneurysm repair using an artificial neural network. J Vasc Surg 2015;62:8e15. 24 Tambyraja A, Murie J, Chalmers R. Predictors of outcome after abdominal aortic aneurysm rupture: edinburgh Ruptured Aneurysm Score. World J Surg 2007;31:2243e337. 25 Chen JC, Hildebrand HD, Salvian AJ, Taylor DC, Strandberg S, Myckatyn TM, et al. Predictors of death in nonruptured and ruptured abdominal aortic aneurysms. J Vasc Surg 1996;24:614e20. 26 Shahidi S, Schroeder TV, Carstensen M, Sillesen H. Outcome and survival of patients aged 75 years and older compared to younger patients after ruptured abdominal aortic aneurysm repair: do the results justify the effort? Ann Vasc Surg 2009;23:469e77. 27 Biancari F, Mazziotti MA, Paone R, Laukontaus S, Venermo M, Lepäntalo M. Outcome after open repair of ruptured abdominal aortic aneurysm in patients>80 years old: a systematic review and meta-analysis. World J Surg 2011;35:1662e70. 28 Opfermann P, von Allmen R, Diehm N, Widmer MK, Schmidli J, Dick F. Repair of ruptured abdominal aortic aneurysm in octogenarians. Eur J Vasc Endovasc Surg 2011;42:475e83.
7 29 Mani K, Björck M, Lundkvist J, Wanhainen A. Improved longterm survival after abdominal aortic aneurysm repair. Circulation 2009;120:201e11. 30 De Rango P, Simonte G, Manzone A, Cieri E, Parlani G, Farchioni L, et al. Arbitrary palliation of ruptured abdominal aortic aneurysms in the elderly is no longer warranted. Eur J Vasc Endovasc Surg 2016;51:802e9. 31 Mehta M, Kreienberg PB, Roddy SP, Paty PS, Taggert JB, Sternbach Y, et al. Ruptured abdominal aortic aneurysm: endovascular program development and results. Semin Vasc Surg 2010;23:206e12. 32 Anain PM, Anain Sr JM, Tiso M, Nader ND, Dosluoglu HH. Early and mid-term results of ruptured abdominal aortic aneurysms in the endovascular era in a community hospital. J Vasc Surg 2007;46:898e905. 33 Yamana H, Moriwaki M, Horiguchi H, Kodan M, Fushimi K, Yasunaga H. Validity of diagnoses, procedures, and laboratory data in Japanese administrative data. J Epidemiol 2017;27:476e 82. 34 Behrendt CA, Debus ES, Mani K, Sedrakyan A. The strengths and limitations of claims based research in countries with fee for service reimbursement. Eur J Vasc Endovasc Surg 2018;56: 615e6. 35 Reimerink JJ, van der Laan MJ, Koelemay MJ, Balm R, Legemate DA. Systematic review and meta-analysis of populationbased mortality from ruptured abdominal aortic aneurysm. Br J Surg 2013;100:1405e13.
Please cite this article as: Yamaguchi T et al., Impact of Endovascular Repair on the Outcomes of Octogenarians with Ruptured Abdominal Aortic Aneurysms: A Nationwide Japanese Study, European Journal of Vascular and Endovascular Surgery, https://doi.org/10.1016/j.ejvs.2019.07.016
Impact of Endovascular Repair on the Outcomes of Octogenarians with Ruptured Abdominal Aortic Aneurysms: A Nationwide Japanese Study Tetsuo Yamaguchi a,b,*, Michikazu Nakai c, Yoko Sumita c, Kunihiro Nishimura c, Toshiyuki Nagai d, Toshihisa Anzai d, Yasushi Sakata e, Hitoshi Ogino f a
Department of Cardiovascular Centre, Toranomon Hospital, Tokyo, Japan Department of Cardiology, Japanese Red Cross Musashino Hospital, Tokyo, Japan c National Cerebral and Cardiovascular Centre, Osaka, Japan d Department of Cardiovascular Medicine, Faculty of Medicine and Graduate School of Medicine Hokkaido University, Sapporo, Japan e Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Osaka, Japan f Department of Cardiovascular Surgery, Tokyo Medical University, Tokyo, Japan b
WHAT THIS PAPER ADDS This nationwide claim based data analysis demonstrated that open surgical repair was less probably to be performed for elderly patients (aged 80 y) with ruptured abdominal aortic aneurysm (rAAA), but endovascular repair (EVAR) was performed similarly. Although old age was an independent predictor of in hospital death for the overall cohort, a small subgroup of elderly patients currently selected for EVAR enjoyed favourable outcomes. Although EVAR for rAAA is not recommended as a first line treatment in current Japanese guidelines, its further implementation, especially in elderly patients with suitable anatomy, may be justified.
Objective: This study aimed to clarify the impact of endovascular aneurysm repair (EVAR) on clinical outcomes in Japanese patients of advanced age with ruptured abdominal aortic aneurysm (rAAA). Methods: This was a national registry based retrospective comparative study, using data from the Japanese Registry Of All cardiac and vascular Diseases-Diagnostic Procedure Combination (JROAD-DPC), a nationwide claim based database from more than 600 hospitals. Patients admitted with rAAA between April 1, 2012, and March 31, 2015 were included in the study. Patient characteristics, management, and outcomes were compared between the elderly (aged 80 y) and the less old. The primary endpoint was in hospital mortality; the secondary endpoint was the functional status at discharge. Results: Of 3 969 eligible patients, 49.9% were categorised as elderly. Elderly patients had a higher prevalence of female gender (41.8% vs. 17.0%, p < .001) and disturbance of consciousness on admission (28.6% vs. 20.7%, p < .001). They were less likely to undergo open surgical repair (31.6% vs. 56.7%, p < .001), although EVAR was performed similarly in both groups (13.7% vs. 14.8%, p ¼ .33). The unadjusted mortality rate (61.8% vs. 37.6%, p < .001) and mean Barthel index at discharge (73.0 vs. 91.8, p < .001) were statistically significantly worse in the elderly. Multilevel mixed effect logistic regression analyses showed that old age was detected as an independent predictor of in hospital death (odds ratio 2.75; 95% confidence interval, 2.39e3.17; p < .001). However, for patients who received EVAR, old age was not statistically significant (odds ratio 1.13; 95% confidence interval, 0.77e1.66; p ¼ .53). Conclusion: Elderly patients with rAAA were less likely to be offered open surgical repair, and the mortality among those who received surgery was high. However, for the small subgroup of elderly patients currently selected for EVAR there was a favourable outcome. The further implementation of EVAR for rAAA in Japan, especially for elderly patients with suitable anatomy, may be justified. Keywords: Elderly patients, Endovascular aneurysm repair, JROAD, Ruptured abdominal aortic aneurysms Article history: Received 28 March 2019, Accepted 14 July 2019, Available online XXX Ó 2019 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.
INTRODUCTION * Corresponding author. Department of Cardiovascular Centre, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo 105e8470, Japan. E-mail address: [email protected] (Tetsuo Yamaguchi). 1078-5884/Ó 2019 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved. https://doi.org/10.1016/j.ejvs.2019.07.016
A ruptured abdominal aortic aneurysm (rAAA) still carries a high mortality.1e3 Previous studies4e6 have reported that only 25e29% of elderly patients (aged 80 years) were offered open surgical repair or endovascular repair (EVAR) for rAAA. Indeed, advanced age is considered a major risk
Please cite this article as: Yamaguchi T et al., Impact of Endovascular Repair on the Outcomes of Octogenarians with Ruptured Abdominal Aortic Aneurysms: A Nationwide Japanese Study, European Journal of Vascular and Endovascular Surgery, https://doi.org/10.1016/j.ejvs.2019.07.016
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factor for early post-operative death.7,8 However, EVAR is potentially suitable and beneficial for elderly patients because of its low invasiveness. Indeed, lower perioperative morbidity rates and similar in hospital mortality rates with EVAR rather than open surgery for rAAA have been shown in previous studies.9e11 EVAR for rAAA and suitable anatomy is recommended as the first line option in the European Society for Vascular Surgery (ESVS) guidelines.12 According to Japanese guidelines,13 EVAR is not recommended for emergency surgery (including rupture) and may be considered only in cases of rupture with stable haemodynamics. Furthermore, few data exist concerning the impact of EVAR on the clinical outcomes in Japanese patients of advanced age with rAAA. The present study compared patient characteristics, management (EVAR, open surgical repair, or conservative treatment) and the outcomes of elderly (aged 80 y) and younger patients with rAAA using the Japanese Registry Of All cardiac and vascular Diseases-Diagnostic Procedure Combination (JROAD-DPC) database. The primary endpoint was in hospital mortality; the secondary endpoint was the functional status at discharge. METHODS Database explanation The JROAD-DPC is a nationwide claim based database based on data from the Japanese DPC/Per Diem Payment System in hospitals participating in the JROAD survey.14 The JROAD database has been described in detail previously.15e17 In brief, all teaching hospitals with cardiovascular beds participate in the JROAD. Hospital doctors must record all admission and discharge data for each patient and are obliged to guarantee their accuracy. This study analysed the JROAD-DPC data from 610 hospitals in 2012, 637 hospitals in 2013, and 742 hospitals in 2014 from all regions in Japan between April 1, 2012, and March 31, 2015.
Tetsuo Yamaguchi et al.
procedures including EVAR, during this period were excluded, because patients transferred to such hospitals might be dead on arrival or unable to undergo surgical treatment. In addition, patients admitted to non-teaching hospitals were excluded to standardise the quality of treatment and data because response rates of teaching hospitals in the JROAD survey were 100%.15 Patients who underwent both EVAR and open surgery were excluded because it could not be determined whether these were intra-operative conversions or planned staged procedures. The cut off age (80 years) was determined by referencing previous studies4e6 and ESVS guidelines.12 The following clinical data were extracted from the database: patient background characteristics; comorbidities; hospital information including bed number, number of aortic procedures per year, and number of cardiovascular surgeons; treatments including operations, drugs, and additional treatments, such as transfusions and vasopressors; in hospital death; consciousness level both on admission and discharge according to the Japan Coma Scale;18,19 and Barthel index (BI) at discharge. Disturbance of consciousness (DOC) was defined as a Japan Coma Scale score of 100e300, as described in a previous report.18 A BI 75 was considered to be a favourable functional status at discharge, according to a previous report.20 Emergency operation was defined as open surgery and/or EVAR performed within one day of admission. Ethical consideration This research plan was designed by the authors and approved by the Institutional Review Board of the Japanese Red Cross Musashino Hospital (approval number: 367). The requirement for informed consent was waived because of the anonymised data. All participants were notified through homepages or posters at each hospital and were told that they were free to opt out of participation at any time. The study complied with the Declaration of Helsinki and Japanese Ethical Guideline for Medical and Health Research involving Human Subjects.
Study participants Patients hospitalised for ruptured aortic aneurysms were identified primarily based on the International Classification of Diseases (ICD)-10 diagnosis codes (ruptured thoracic aortic aneurysm: I711; ruptured abdominal aortic aneurysm: I713; and ruptured thoracic-abdominal aortic aneurysm: I715). In the JROAD-DPC database, aortic dissections and non-ruptured aortic aneurysms are clearly distinguished from ruptured aortic aneurysms. Diagnosis and comorbidities were primarily defined based on the ICD-10 codes, but they were also checked by the physicians to examine whether they matched the treatments performed for each patient and to determine whether these were compatible with the code data.14 Additionally, the diagnosis written in Japanese in the DPC database was used to increase the accuracy of the diagnosis.17 Patients admitted to hospitals that did not perform any cardiovascular
Statistical analyses Data were expressed as the mean and standard deviation for normally distributed variables and as median with the interquartile range for non-normally distributed data. Continuous variables were compared by Student’s t test or the ManneWhitney U test as appropriate. Categorical data were expressed as numbers and percentages and compared by the chi-square test or Fisher’s exact test. Multilevel mixed effect logistic regression analyses using institutional codes as random intercepts were performed to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) for the in hospital death of the elderly patient group compared with the younger patients, adjusted for gender, history of heart failure, chronic obstructive pulmonary disease, diabetes mellitus, cerebrovascular disease, renal failure on admission, DOC on admission, the need for vasopressor
Please cite this article as: Yamaguchi T et al., Impact of Endovascular Repair on the Outcomes of Octogenarians with Ruptured Abdominal Aortic Aneurysms: A Nationwide Japanese Study, European Journal of Vascular and Endovascular Surgery, https://doi.org/10.1016/j.ejvs.2019.07.016
EVAR for Elderly Japanese rAAA Patients
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administration in the emergency department, hospital bed number, and number of cardiovascular surgeons. These variables were selected according to their clinical importance based on previous studies.8,21e25 Discrimination of the selected variables was confirmed by a receiver operator characteristics (ROC) analysis. Furthermore, as sensitivity analyses, additional logistic regression analyses were performed using another cut off age made by the ROC analysis for in hospital death. Statistical analyses were performed by a physician (Yamaguchi T) and a statistician (Nakai M) using the Stata software program, ver. 14.2 (StataCorp, College Station, TX, USA). A two sided p value < .05 was considered statistically significant.
higher prevalence of DOC on admission than younger patients (28.6% vs. 20.7%, p < .001). Elderly patients were transferred to hospitals with fewer cardiovascular surgeons and annual aortic procedures than younger patients. The baseline characteristics of the patients stratified by age group and treatments performed are shown in Table S1. Overall, patients who were managed medically were older with a lower body mass index and markedly higher prevalence of DOC on arrival, and they were transferred to hospitals with fewer cardiovascular surgeons and annual aortic procedures in both groups.
RESULTS
Fig. 2 shows the key outcomes of this study, and Table 2 shows the treatments and outcomes comparing the elderly and younger patients. A small number of patients (elderly: 2.5% [49/1 982], younger: 3.5% [69/1 987]) received delayed (more than one day after arrival) operative treatment. Elderly patients were less likely to undergo emergency operation (42.8% vs. 68.0%, p < .001) and open surgical repair (31.6% vs. 56.7%, p < .001) than younger patients. However, EVAR was performed at a similar rate in both groups (13.7% vs. 14.8%, p ¼ .33), and the ratio of EVAR to open surgery was much higher in the elderly patients than in the younger patients (43.5% vs. 26.1%, p < .001). The unadjusted in hospital mortality rate of elderly patients was statistically significantly worse than that in the younger patients (61.8% vs. 37.6%, p < .001).
Patient characteristics A total of 8 032 patients (aged 20 years) admitted with a primary diagnosis of ruptured aortic aneurysm from April 1, 2012, to March 31, 2015, were extracted from the database. The patient selection flowchart is shown in Fig. 1. A total of 7 086 patients from 564 hospitals were identified and 3 991 had rAAA. After excluding non-eligible patients, 1 982 patients (49.9%) were elderly (aged 80 years). The baseline characteristics of the patients stratified by age group are shown in Table 1. Female patients were dominant in the elderly group compared with the young group (41.8% vs. 17.0%, p < .001). The elderly showed a statistically significantly lower body mass index (21.2 vs. 23.3, p < .001) and a
Clinical outcomes
Patients with ruptured aortic aneurysms (n=8 302)
Patients asmitted to hospitals not performing any cardiovascular operations (n=1 026)
Patients admitted to non-teaching hospitals (n=190)
Patients from 564 hospitals (n = 7 086) Thoracic aneurysm (n=2 700)
Thoraco-abdominal aneurysm (n=395)
Abdominal aneurysm (n=3 991) Missing data for age (n=2)
Patients who underwent both EVAR and open surgery (n=20)
Study population (n=3 969)
Octogenarians (n=1 982)
Younger group (n=1 987)
Figure 1. Study flow chart. EVAR ¼ endovascular aneurysm repair.
Please cite this article as: Yamaguchi T et al., Impact of Endovascular Repair on the Outcomes of Octogenarians with Ruptured Abdominal Aortic Aneurysms: A Nationwide Japanese Study, European Journal of Vascular and Endovascular Surgery, https://doi.org/10.1016/j.ejvs.2019.07.016
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Tetsuo Yamaguchi et al.
Table 1. Baseline characteristics of 3 969 Japanese patients with ruptured abdominal aortic aneurysm, stratified by age group Parameter
Octogenarians Younger (n [ 1982) patients (n [ 1987)
Age e y 86.2 4.3 Female gender 829 (41.8) Body mass index e kg/m2 21.2 4.6 Medical history Heart failure 181 (9.1) Myocardial infarction 55 (2.8) Cerebrovascular disease 145 (7.3) COPD 69 (3.5) Diabetes mellitus 133 (6.7) Renal failure on 156 (7.9) admission Need for additional treatment Transfusion 1080 (54.5) Vasopressor 982 (49.5) Disturbance of 567 (28.6) consciousness on arrival Institutional parameters Number of beds (missing n ¼ 1) 20e100 beds 20 (1.0) 100e200 beds 39 (2.0) 200e300 beds 114 (5.8) 300e450 beds 439 (22.1) 450e750 beds 993 (50.1) > 750 beds 377 (19.0) Number of cardiovascular 5.0 (3.0e7.0) surgeons Number of certified 6.0 (4.0e10.0) cardiologists Annual aortic procedures 116.2 89.2 Annual endovascular 34.1 33.3 aneurysm repair Data are medians defined COPD ¼
p
69.7 7.3 337 (17.0) 23.3 4.7
<.001 <.001 <.001
227 (11.4) 63 (3.2) 133 (6.7) 69 (3.5) 202 (10.2) 167 (8.4)
.017 .46 .44 .99 <.001 .54
1492 (75.1) 1373 (69.1) 412 (20.7)
<.001 <.001 <.001
.88 18 (0.9) 44 (2.2) 125 (6.3) 417 (21.0) 991 (49.9) 391 (19.7) 5.0 (3.0e8.0) <.001 7.0 (4.0e11.0) .002 124.3 89.7 37.6 34.0
.005 <.001
expressed as numbers (%), means standard deviations, or (interquartile range). A disturbance of consciousness was as a Japan Coma Scale of from 100 to 300. chronic obstructive pulmonary disease.
Similarly, patients who were discharged with a favourable functional status (BI 75) were statistically significantly less frequent among elderly patients than among younger patients (55.3% vs. 85.0%, p < .001). Table S2 shows the outcomes by each treatment comparing the elderly and the young. Unadjusted mortality was higher in the elderly patients for all types of management than in younger patients. The mortality rate with conservative therapy in this database was 89.9% in the elderly patients and 82.2% in the young patients. Table 3 shows the results of multilevel mixed effect logistic regression analyses for in hospital death. In the multivariable analyses, the area under the curve (AUC) of the selected variables in the ROC curve was 0.85 (95% CI 0.84e0.86). Old age (cut off: 80 years) was detected as an independent predictor of in hospital death in the overall cohort after adjusting for covariates (OR 2.43; 95% CI 2.06e 2.87; p < .001). This trend was similar when analyses were
performed for the patients receiving open surgery and medical management. However, only for patients who underwent EVAR, was old age not statistically significant (OR 1.13; 95% CI 0.77e1.66; p ¼ .53). Similar results were confirmed when analyses were performed at another cut off age (76 years) determined by the ROC analysis (Table 3). DISCUSSION This is the largest population based study to compare the characteristics, management, and outcomes of elderly Japanese patients with rAAA with those of younger patients. The main finding was that although elderly patients had a worse overall mortality rate and functional status at discharge than younger patients, those who received EVAR showed a comparable outcome to younger patients. Previous studies have shown a low rate of emergency surgery (25e29%) for rAAA in elderly patients.4e6 A similar trend was noted in the present study, where statistically significantly fewer elderly patients with rAAA underwent emergency operations than younger patients (42.8% vs. 68.0%, p < .001). This may be because of their older age and more severe clinical presentation, such as a higher rate of DOC on arrival, than in younger patients. Older age can be related to delayed or missed diagnosis of aortic aneurysms, which can result in a more severe clinical presentation. Previous studies have shown that although elderly patients have a significantly higher risk of post-operative death compared with younger patients, open surgical repair has been life saving in 33% of elderly patients,26 and the mortality rate of 59% in the pooled analysis of 36 studies was deemed acceptable.27 In the present study, the mortality rate of elderly patients receiving open surgery was also acceptable at 28.8%, which was similar to the 30 day mortality of 26.7% from a tertiary referral centre.28 In addition, the intermediate survival rates (at one, two and three years after surgery) of elderly patients with rAAA are also reported to be acceptable (82%, 76%, and 69%, respectively).29 For these reasons, the ESVS guideline recommends that advanced age alone should not prevent surgery for rAAA. Because elderly patients have more comorbidities than younger patients, EVAR may be more beneficial for the former population because of its low invasiveness. In the present study, the ratio of EVAR to open surgery was much higher in the elderly patients than in the younger ones (43.5% vs. 26.1%, p < .001). Furthermore, a multivariable analysis showed that elderly patients receiving EVAR enjoyed comparable outcomes to younger patients. Similar results were reported in a previous study,30 showing that the peri-operative mortality in elderly patients was higher than that in younger patients, although not to a statistically significant degree when only EVAR was performed. Previous studies have shown that, with the advancements in endografts, nearly 80% of patients can be treated by EVAR,31 and three quarters of patients with rAAA can be considered for EVAR, regardless of their haemodynamic
Please cite this article as: Yamaguchi T et al., Impact of Endovascular Repair on the Outcomes of Octogenarians with Ruptured Abdominal Aortic Aneurysms: A Nationwide Japanese Study, European Journal of Vascular and Endovascular Surgery, https://doi.org/10.1016/j.ejvs.2019.07.016
Proportion of favourable in hospital outcome – %
EVAR for Elderly Japanese rAAA Patients
5
p <.001
100 80
p < .001
31.6
20 0
61.8
56.7
60 40
85.0
p < .001
55.3 37.6
p = .33 13.7 14.8
Open surgical repair
Endovascular repair Octogenarians
In-hospital death
Favourable functional status at discharge
Younger
Figure 2. A comparison of key in hospital outcomes between octogenarians and younger patients. A favourable functional status at discharge was defined as a Barthel index 75. Results from a population based analysis of 3 969 Japanese patients with ruptured abdominal aortic aneurysm.
status.32 For these reasons, EVAR for rAAA, especially in elderly patients, can be performed widely in Japan if the anatomy is suitable. There are several limitations with the present study. First, because this study was a retrospective analysis of claim based data, there may be risks of systemic or nonsystemic coding errors or insufficient data collection. However, the validity of the DPC database is generally high, especially for primary diagnoses and procedure records.33 In addition, because these coding errors are likely to affect all comparison groups equally, comparative studies may be useful. Although attempts were made to adjust for confounders as much as possible using clinically important predictors and the discrimination power of the selected variables was relatively high (AUC: 0.85), unadjusted confounding factors may have existed. Second, the DPC database does not include detailed data on the aortic anatomy, such as aneurysm neck length, Fitzgerald classification, type of stent graft implanted, duration from onset to arrival, or blood pressure at arrival, blood pressure management, and pre-operative volume resuscitation.
Table 2. Treatments and clinical outcomes of 3969 Japanese patients with ruptured abdominal aortic aneurysm, stratified by age group Parameter Management Medical management Emergency repair < 24 h Delayed repair Open surgical repair Endovascular repair Endovascular repair/open surgical repair Clinical outcomes In hospital death Barthel index at discharge Favourable functional status at discharge Other outcomes Length of hospitalisation e d
Octogenarians (n [ 1982)
Younger patients (n [ 1987)
p
1084 (54.7) 849 (42.8) 49 (2.5) 626 (31.6) 272 (13.7) 272/626 (43.4)
567 (28.5) 1351 (68.0) 69 (3.5) 1126 (56.7) 294 (14.8) 294/1126 (26.1)
<.001 <.001 .064 <.001 .33 <.001
1225 (61.8) 73.0 (30.5) 419/757 (55.4)
748 (37.6) 91.8 (19.6) 1053/1239 (85.0)
<.001 <.001 <.001
24 (16e37)
22 (15e34)
.011
Data are expressed as numbers (%), or medians (interquartile range). Emergency operation was defined as open surgery and/or endovascular aneurysm repair performed within one day of admission. A favourable functional status was defined as a Barthel index at discharge 75.
Table 3. Multivariable logistic regression analyses for risk of in hospital death stratified by management approach Age groups
Overall in hospital mortality* OR
Younger Octogenarians Elderly (cut off: 76)
95% CI
1 (Reference) 2.43 2.06e2.87 2.40 2.03e2.85
In hospital mortality after open surgical repair* p
OR
<.001 <.001
1 (Reference) 1.88 1.45e2.44 1.93 1.49e2.49
95% CI
In hospital mortality after endovascular repair*
p
OR
<.001 <.001
1 (Reference) 1.13 0.77e1.66 1.26 0.84e1.89
95% CI
In hospital mortality after medical treatment*
p
OR
.53 .26
1 (Reference) 2.53 1.71e3.72 2.72 1.79e4.13
95% CI
p <.001 <.001
Results from a population based analysis of 3969 Japanese patients with ruptured abdominal aortic aneurysm. OR ¼ odds ratio; CI ¼ confidence interval. * Adjusted for gender, history of heart failure, chronic obstructive pulmonary disease, diabetes mellitus, cerebrovascular disease, renal failure on admission, disturbance of consciousness on admission, the need for vasopressor administration in the emergency department, hospital bed number, and number of cardiovascular surgeons.
Please cite this article as: Yamaguchi T et al., Impact of Endovascular Repair on the Outcomes of Octogenarians with Ruptured Abdominal Aortic Aneurysms: A Nationwide Japanese Study, European Journal of Vascular and Endovascular Surgery, https://doi.org/10.1016/j.ejvs.2019.07.016
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However, renal failure at admission, DOC at admission, and the need for vasopressor administration in the emergency department in the multivariable analyses were used as surrogates for unstable haemodynamics and a low blood pressure on admission. Third, it was not possible to determine indications for treatment, so the possibility of selection bias cannot be ruled out. However, claim based databases have strengths of including treatments performed by large numbers of healthcare providers and medical specialties, no selection bias by physicians, and high external validity, as no reimbursement is received without the submission of data to the funder.34 Fourth, the non-surgery rate was very high in this study. Because some of the hospitals participating in this study are not the large operating centres, patients managed medically may include those who arrived at the hospital almost dead, and those who could not undergo surgery because of severe complications. A previous meta-analysis35 showed that the non-surgery rate for rAAA was nearly 40%, which was similar to that noted in the present study. Considering publication bias, the non-surgery rate of non-referral centres may be higher than 40%. Therefore, it is considered that this high non-surgery rate reflects the real world situation in Japan. The mortality rates of patients who were managed medically in the same meta-analysis35 range between 75% and 90%, which was also similar to the present results. Finally, it was only possible to evaluate the in hospital outcomes and not the longer term outcomes. CONCLUSIONS The present analysis of a nationwide administrative database demonstrated that elderly patients with rAAA had worse in hospital mortality and functional status at discharge than young patients. Elderly patients with rAAA were less likely to be offered open surgical repair, and the mortality among those who received surgery was high. However, the small subgroup of elderly patients currently selected for EVAR showed a favourable outcome. Further implementation of EVAR for rAAA in Japan, especially for elderly patients with suitable anatomy, may be justified. CONFLICT OF INTEREST None. FUNDING None. APPENDIX A. SUPPLEMENTARY DATA Supplementary data to this article can be found online at https://doi.org/10.1016/j.ejvs.2019.07.016. REFERENCES 1 Hoornweg LL, Storm-Versloot MN, Ubbink DT, Koelemay MJ, Legemate DA, Balm R. Meta analysis on mortality of ruptured abdominal aortic aneurysms. Eur J Vasc Endovasc Surg 2008;35: 558e70.
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Please cite this article as: Yamaguchi T et al., Impact of Endovascular Repair on the Outcomes of Octogenarians with Ruptured Abdominal Aortic Aneurysms: A Nationwide Japanese Study, European Journal of Vascular and Endovascular Surgery, https://doi.org/10.1016/j.ejvs.2019.07.016