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Pre-Emptive Embolization of the Aneurysm Sac or Aortic Side Branches in Endovascular Aneurysm Repair: Meta-Analysis and Trial Sequential Analysis of Randomized Controlled Trials
Vascular Surgery Unit, Department of Cardiothoracic and Vascular Surgery, University General Hospital of Heraklion, School of Medicine, University of Crete, Heraklion, Greece
Cardiac Surgery Unit, Department of Cardiothoracic and Vascular Surgery, University General Hospital of Heraklion, School of Medicine, University of Crete, Heraklion, Greece
Vascular Surgery Unit, Department of Cardiothoracic and Vascular Surgery, University General Hospital of Heraklion, School of Medicine, University of Crete, Heraklion, Greece
Correspondence to: George A. Antoniou, MD, PhD, MSc, FEBVS, Room G37, Vascular Offices, J Block, The Royal Oldham Hospital, Rochdale Road, OL1 2JH Oldham, UK
Department of Vascular and Endovascular Surgery, Manchester University NHS Foundation Trust, Manchester, UKDivision of Cardiovascular Sciences, School of Medical Sciences, Manchester Academic Health Science Centre, The University of Manchester, Manchester, UK
To investigate outcomes of pre-emptive embolization of the aneurysm sac or aortic side branches in endovascular aneurysm repair (EVAR).
Methods
The review was reported as per Preferred Reporting Items for Systematic reviews and Meta-Analyses 2020 with a preregistered protocol. Bibliographic sources (MEDLINE, Embase, and CENTRAL) were searched using subject headings and free text terms. Randomized controlled trials comparing EVAR with versus without embolization were included. Pooled estimates of dichotomous outcomes were calculated using odds ratio (OR) or risk difference (RD) and 95% confidence interval (CI) applying the Mantel–Haenszel method. Continuous outcomes were summarized using mean difference (MD) and 95% CI applying the inverse variance method. The certainty of evidence was appraised with the Grading of Recommendations Assessment, Development, and Evaluation framework. Version 2 of the Cochrane tool was used to assess the risk of bias. Trial sequential analysis assumed alpha = 5% and power = 80%.
Results
Four randomized controlled trials were included. No significant difference was found in aneurysm-related mortality (RD 0.00, 95% CI −0.03 to 0.03), overall mortality (OR 1.85, 95% CI 0.42–8.13), aneurysm rupture (RD 0.00, 95% CI −0.03 to 0.03), type II endoleak-related reintervention (RD -0.07, 95% CI −0.21 to 0.06), procedure time (MD 20.12, 95% CI −11.54 to 51.77), or fluoroscopy time (MD 11.17, 95% CI −11.22 to 33.56). Patients with pre-emptive embolization had significantly lower odds of type II endoleak (OR 0.45, 95% CI 0.26–0.78) and sac expansion (OR 0.19, 95% CI 0.07–0.52). The risk of bias was high for all outcomes. The certainty of evidence was very low for all outcomes, except for type II endoleak, for which it was low. Trial sequential analysis showed an inconclusive result for overall mortality and type II endoleak-related reintervention but confirmed the advantage of embolization in reducing type II endoleak and sac expansion.
Conclusions
Limited, low certainty data suggest pre-emptive embolization confers no clinical benefits in EVAR.
Introduction
Endovascular repair is the mainstay of treatment for abdominal aortic aneurysm (AAA).
Editor's Choice - European Society for Vascular Surgery (ESVS) 2019 clinical practice guidelines on the management of abdominal aorto-iliac artery aneurysms.
With the accumulated clinical experience and technological advancements, a broader range of aortic anatomies can be treated inside the instructions for use of newer generation devices.
Despite such advances, type II endoleak remains a common occurrence after endovascular aneurysm repair (EVAR). Although it is considered a benign condition, it requires close follow-up and has the potential of causing severe late complications.
Indeed, a type II endoleak may cause the aneurysm sac to expand as a result of continuous sac pressurization, in which case treatment is required to avoid adverse sequela, such as graft migration, type I or III endoleak, and ultimately rupture. In case of sac expansion caused by a type II endoleak, the first-line treatment is embolization of the culprit vessel or aneurysm sac via the transarterial or translumbar route. Despite high rates of technical success, such procedures may be technically challenging.
A meta-analysis of translumbar embolization versus transarterial embolization for type II endoleak after endovascular repair of abdominal aortic aneurysm.
Open surgical repair is an option in case of failure of endovascular treatment strategies and continuing sac expansion.
Emerging evidence suggests that preventive embolization of aortic side branches or the aneurysm sac itself during the index EVAR procedure may be safe and result in lower rates of type II endoleak and secondary interventions and a higher rate of sac regression.
There is currently no meta-analysis of all published randomized controlled trials (RCTs) comparing EVAR with and without embolization. We sought to investigate whether pre-emptive aortic branch or aneurysm sac embolization performed at the same time as the standard EVAR confers improved clinical outcomes compared to standard EVAR alone.
Methods
Review Design and Protocol Registration
The objectives and methodology of our review were prespecified in a protocol, which was registered in PROSPERO (international prospective register of systematic reviews) under the registration number CRD42022311333. No amendments to the review protocol were made during the review conduct. The review was developed in line with principles and methodology described in the Cochrane Handbook for Systematic Reviews of Interventions.
Eligible participants were male or female patients of any age who underwent standard endovascular repair for intact infrarenal AAA with or without preventive embolization of aortic side branches or the aneurysm sac.
Types of intervention
The intervention of interest was preventive embolization of patent aortic side branches arising from the AAA sac, such as the lumbar arteries or the inferior mesenteric artery (IMA), and/or preventive embolization of the AAA sac. Such interventions could have been performed with coils, glue, or plugs. Embolization of aortic side branches could have been performed either at the same time as the index EVAR or in a different setting but within 3 months prior to the EVAR. No restriction to size, number, or type of embolized branch(es) was applied. The control intervention was standard EVAR without pre-emptive embolization.
Types of outcome measures
Primary outcomes were:
•
Aneurysm-related mortality.
•
All-cause mortality.
•
Aneurysm rupture.
Secondary outcomes were:
•
Type II endoleak.
•
Type II endoleak-related reintervention.
•
Procedure and fluoroscopy time.
•
Aneurysm sac expansion.
Studies should report at least one primary or secondary outcome to be eligible for this review. No other study eligibility criteria were applied, for example, language or recruitment period.
Information Sources and Search Strategy
The literature search strategy was developed by a review author (G.A.) with experience in outreach, knowledge, and evidence search. The PICO (patient, intervention, comparison, and outcome) approach was used to form search strategies. Access to healthcare databases was via online sources of institutional library services. MEDLINE (Medical Literature Analysis and Retrieval System Online) and Embase (Excerpta Medica Database) were searched using the Ovid interface. The following limits were applied: “humans,” "year 2000 to current," and "all adult (19+ years)." The Cochrane Central Register of Controlled Trials (CENTRAL) was also searched for eligible RCTs. A combination of controlled vocabulary (subject headings) and free text terms was used to search electronic literature sources. Subject headings/thesaurus trees, search operators, and search limits in each of the above databases were adapted accordingly. Electronic searches were last run in March 2022. Search syntaxes are presented in Appendix 1. A second-level search was conducted by interrogating the bibliographic list of articles that qualified for inclusion in this review.
Study Selection and Data Collection Process
Two review authors (N.G. and M.K.) conducted the prespecified literature searches and evaluated the eligibility of studies against the inclusion criteria independently. When disagreement arose, a third review author (N.K.) acted as an arbitrator. Articles published in a non-English language were translated to determine eligibility, assess the risk of bias, and extract relevant data.
Data to be collected from individual studies were prespecified during the development of the review protocol. Additional relevant data identified during the data collection process were extracted and entered into a Microsoft Excel spreadsheet. Two independent review authors (N.G. and M.K.) extracted data from the selected studies. The collected data were then crosschecked by a third review author (N.K.). Data were extracted from the main text, figures, and tables of the original publications. Only published material was considered and no study investigators were contacted to obtain or confirm relevant information. Data items were grouped as follows:
•
Study level data: first author, journal where the study was published, year of publication, study period, country where the study was conducted, single or multicenter study, inclusion criteria for participant enrollment, information on the intervention of interest (embolization), number of patients in each group, technical success, complications, and length of follow-up.
•
Individual study population data: male gender, age, and maximum AAA diameter.
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Data pertaining to risk of bias assessment.
•
Outcome data, as outlined in the “Eligibility criteria” section.
Study Risk of Bias Assessment and Evidence Appraisal
Version 2 of the Cochrane risk-of-bias tool for randomized trials (RoB 2) was used to assess the risk of bias in RCT included in this review.
The tool, that is outcome-based, is structured into 5 domains through which bias might be introduced into the result: bias arising from the randomization process, bias due to deviations from intended interventions, bias due to missing outcome data, bias in measurement of the outcome, and bias in selection of the reported result. The tool gives the option for an overall predicted direction of bias for a specific outcome. An Excel tool was used to implement RoB 2. Two review authors (N.G. and N.K.) assessed the risk of bias in studies independently; a third review author acted as an arbitrator in case of disagreement.
The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework was used to appraise the certainty of the body of evidence for specific outcomes.
The GRADE approach results in an assessment of the quality of the body of evidence in one of 4 grades: high, moderate, low, and very low. Factors determining the quality of evidence are limitations in study design or execution, inconsistency of results, indirectness of evidence, imprecision, publication bias, magnitude of effect, plausible confounding, and dose-response gradient. Summary of findings tables were generated using an online platform (https://gdt.gradepro.org/app/).
Synthesis Methods
For binary outcomes, the effect measure used in the synthesis was the odds ratio (OR) or risk difference (RD) and 95% confidence interval (CI). The RD was calculated when no events were reported in both groups.
For continuous outcomes, the effect measure used was the mean difference (MD) and 95% CI.
All studies reporting the primary and secondary outcomes were eligible for data synthesis. Number of events and total number of patients in each group for dichotomous outcomes and mean value, corresponding standard deviation (SD), and total number of patients in each group were inputted into the RevMan computer program (Version 5.4, Copenhagen: The Nordic Cochrane Center, The Cochrane Collaboration, 2020). Effect estimates for binary outcomes were calculated using the Mantel–Haenszel statistical method and those for continuous outcomes were calculated using the inverse variance method. A forest plot was generated for graphical presentation of meta-analysis for each outcome.
Because of the anticipated between-study heterogeneity, for example, different methods of embolization, random-effects models proposed by DerSimonian and Laird were used for all meta-analyses.
The extent and impact of between-study heterogeneity were assessed by inspecting the forest plots and by calculating the tau-squared and the I-squared statistics, respectively. Inconsistency was quantified and interpreted with the following guide: 0% to 40% might not be important; 30% to 60% may represent moderate heterogeneity; 50% to 90% may represent substantial heterogeneity; and 75% to 100% may represent considerable heterogeneity.
To explore possible causes of heterogeneity, a subgroup analysis was conducted for patients who had aortic side branch embolization versus those who had aneurysm sac embolization.
Sensitivity analyses were conducted to explore the robustness of the meta-analyses by excluding studies that were deemed to be of high risk of bias. Furthermore, the analyses were repeated after removing one study at a time to examine the impact of each study on the overall meta-analysis.
To assess risk of bias due to missing results in a synthesis arising from reporting biases, the effect by the inverse of its standard error would be plotted for each study. The possibility of publication bias would be assessed both visually evaluating the symmetry of the funnel plot and mathematically using the Egger's regression intercept for outcomes reported by at least 10 studies.
Trial sequential analysis was used to quantify the statistical reliability of data in the cumulative meta-analysis adjusting significance levels for sparse data and repetitive testing on accumulating data.
To control for type I error, the thresholds for statistical significance were adjusted using the O'Brien-Fleming α-spending function to account for the elevated risk of random error, when the required information size was not surpassed. Furthermore, the test statistic itself was penalized in congruence with the strength of the available evidence. To control for type II error, adjusted thresholds for nonsuperiority and noninferiority were constructed using the β-spending function and futility boundaries. The information size was estimated based on 80% power and 5% type 1 error. The incidence in the intervention and control arm was calculated with the Comprehensive Meta-Analysis software (Biostat, Englewood, New Jersey, USA) by pooling incidence rates reported in the included trials in a proportion meta-analysis. The trial sequential analysis was conducted using an open-source software: Trial Sequential Analysis (Computer program) Version 0.9.5.10 Beta, The Copenhagen Trial Unit, Center for Clinical Intervention Research, The Capital Region, Copenhagen University Hospital–Rigshospitalet, 2021.
Results
Results of the Literature Search and Characteristics of Included Studies
Electronic literature searches retrieved 2,238 reports. Four RCTs were eligible for inclusion in this review.
The 4 RCTs reported a total of 393 patients, of whom 194 were allocated to the intervention group and 199 to the control group. Three hundred eighty two patients received the treatment they were assigned to (197 standard EVARs and 185 pre-emptive embolizations). Three of the studies included only patients who were deemed high risk for type II endoleak. Eligibility criteria for participant inclusion in the individual studies and definitions for high risk for type II endoleak are presented in Table I. Various agents were used for sac or side branch embolization, such as coils, fibrin glue, and plugs. The technical success rate of embolization ranged across the trials from 89% to 100%. No perioperative complications resulting from sac or branch embolization were reported. The follow-up period ranged across the studies from 16 to 24 months. Two trials reported separate outcomes for a third group of patients, who were considered low risk for type II endoleak.
Defined as patent IMA with a luminal diameter at its origin > 3 mm, ≥ 3 pairs of patent lumbar arteries, or 2 pairs of lumbar arteries and a median sacral artery or an accessory renal artery.
Sac embolization with volume-dependent number of coils
EVAR, endovascular aneurysm repair; IMA, inferior mesenteric artery; NR, not reported; SD, standard deviation
a Defined as patent IMA and ≥ 2 pairs of lumbar arteries.
b Defined as patent IMA ≥ 3 mm, lumbar artery ≥ 2 mm, or aorto-iliac aneurysm.
c Defined as patent IMA with a luminal diameter at its origin > 3 mm, ≥ 3 pairs of patent lumbar arteries, or 2 pairs of lumbar arteries and a median sacral artery or an accessory renal artery.
d Not specifically defined but refers to both control and intervention groups.
e Defined as successful IMA embolization.
f Mean and SD.
g Target follow-up period for the study population.
A summary of methods used to describe changes in AAA size is provided in Supplementary Table 1. Data on sac growth were explicitly reported in 2 studies.
In the other 2, data on sac expansion were extracted from the number of reinterventions because the authors reported that secondary interventions were indicated in case of AAA sac enlargement.
Results of Data Synthesis, Risk of Bias Assessment, and Certainty of Evidence Appraisal
The results of risk of bias assessments are presented in Figure 2. The forest plots for the primary and secondary outcomes are presented in Figure 3. The results of the GRADE assessment for the individual outcomes are summarized in Table III.
Fig. 2Results of risk of bias assessment for the individual outcomes using the Cochrane Risk of Bias 2 tool. (A) aneurysm-related mortality, (B) overall mortality, (C) aneurysm rupture, (D) Type II endoleak, (E) Type II endoleak related-reintervention, (F) procedure duration, (G) fluoroscopy time, and (H) aneurysm sac expansion.
Fig. 2Results of risk of bias assessment for the individual outcomes using the Cochrane Risk of Bias 2 tool. (A) aneurysm-related mortality, (B) overall mortality, (C) aneurysm rupture, (D) Type II endoleak, (E) Type II endoleak related-reintervention, (F) procedure duration, (G) fluoroscopy time, and (H) aneurysm sac expansion.
Fig. 3Forest plots for the comparison embolization versus standard EVAR. The solid squares denote the odds ratios, risk differences, or mean differences; the horizontal lines represent the 95% confidence intervals; and the diamonds denote the pooled odds ratios, risk differences, or mean differences. (A) aneurysm-related mortality, (B) overall mortality, (C) aneurysm rupture, (D) Type II endoleak, (E) Type II endoleak-related reintervention, (F) procedure duration, (G) fluoroscopy time, and (H) sac expansion. CI, confidence interval; EVAR, endovascular aneurysm repair; IV, inverse variance; M-H, Mantel–Haenszel; SD, standard deviation.
Fig. 3Forest plots for the comparison embolization versus standard EVAR. The solid squares denote the odds ratios, risk differences, or mean differences; the horizontal lines represent the 95% confidence intervals; and the diamonds denote the pooled odds ratios, risk differences, or mean differences. (A) aneurysm-related mortality, (B) overall mortality, (C) aneurysm rupture, (D) Type II endoleak, (E) Type II endoleak-related reintervention, (F) procedure duration, (G) fluoroscopy time, and (H) sac expansion. CI, confidence interval; EVAR, endovascular aneurysm repair; IV, inverse variance; M-H, Mantel–Haenszel; SD, standard deviation.
with a total of 166 patients (80 in the pre-emptive embolization group and 86 in the control group). No aneurysm-related death occurred in either treatment arm (RD 0.00, 95% CI -0.03 to 0.03, P = 1; test for heterogeneity: P = 1.0, I2 = 0%). The overall risk of bias was high, and the quality of evidence was very low.
Overall mortality: Data on overall mortality were reported in 2 studies,
with a total of 166 patients (80 in the pre-emptive embolization group and 86 in the control group). Meta-analysis showed no statistically significant difference in overall mortality between the treatment arms (OR 1.85, 95% CI 0.42–8.13, P = 0.42; test for heterogeneity: P = 0.64, I2 = 0%). The overall risk of bias was high, and the quality of evidence was very low.
Aneurysm rupture: Data on aneurysm rupture were reported in 2 studies,
with a total of 166 patients (80 in the pre-emptive embolization group and 86 in the control group). No rupture occurred in either treatment arm (RD 0.00, 95% CI -0.03 to 0.03, P = 1; test for heterogeneity: P = 1.0, I2 = 0%). The overall risk of bias was high, and the quality of evidence was very low.
Type II endoleak: Data on type II endoleak were reported in all trials,
with a total of 358 patients (174 in the pre-emptive embolization group and 184 in the control group). The odds of type II endoleak were lower in patients who underwent pre-emptive embolization with the difference being statistically significant (OR 0.45, 95% CI 0.26–0.78; P = 0.004; test for heterogeneity: P = 0.60, I2 = 0%). The overall risk of bias was high, and the quality of evidence was low. Meta-analyses for type II endoleak at different time points are presented in Supplementary Figure 1.
Type II endoleak-related reintervention: Data on type II endoleak-related reintervention were reported in 3 studies,
with a total of 305 patients (150 in the pre-emptive embolization group and 155 in the control group). Meta-analysis showed no statistically significant difference in the odds of type II endoleak-related reintervention between the treatment arms (RD -0.07, 95% CI -0.21 to 0.06, P = 0.30; test for heterogeneity: P = 0.0001, I2 = 89%). The overall risk of bias was high, and the quality of evidence was very low.
Procedure time: Data on procedural time were reported in 2 studies,
with a total of 211 patients (103 in the pre-emptive embolization group and 108 in the control group). Meta-analysis showed no statistically significant difference in the duration of the procedure between the treatment arms (MD 20.12, 95% CI -11.54 to 51.77; P = 0.21; test for heterogeneity: P = 0.09, I2 = 66%). The overall risk of bias was high, and the quality of evidence was very low.
Fluoroscopy time: Data on fluoroscopy time were reported in 2 studies,
with a total of 211 patients (103 in the pre-emptive embolization group and 108 in the control group). The difference in fluoroscopy time between the groups was not statistically significant (MD 11.17, 95% CI -11.22 to 33.56; P = 0.33; test for heterogeneity: P = 0.004, I2 = 88%). The overall risk of bias was high, and the quality of evidence was very low.
Aneurysm sac expansion: A total of 391 patients (192 in the pre-emptive embolization group and 199 in the control group) were included in meta-analysis for sac expansion. The odds of sac expansion were significantly lower in patients with pre-emptive embolization (OR 0.19, 95% CI 0.07–0.52; P = 0.001; test for heterogeneity: P = 0.83, I2 = 0%). The overall risk of bias was high, and the quality of evidence was very low.
Subgroup and sensitivity analyses
Subgroup analyses for method of embolization (aneurysm sac versus side branch) showed that the direction of the effect estimate was not affected for any of the outcomes. Meta-analyses of studies that used sac embolization, thus excluding the study that reported side branch embolization, affected the significance of effect estimates as follows:
1
The difference in type II endoleak became non-significant (OR 0.56 95% CI 0.28–1.15, P = 0.11; heterogeneity: P = 0.60, I2 = 0%).
2
The difference in type II endoleak-related reintervention became statistically significant in favor of pre-emptive sac embolization (RD -0.12 95% CI -0.19 to 0.04, P = 0.002; heterogeneity: P = 0.78, I2 = 0%).
Prespecified sensitivity analyses did not affect the direction or statistical significance of the effect estimate for any of the outcomes.
Trial sequential analysis
A graphical presentation of the results of trial sequential analyses is presented in Figure 4. Analysis of embolization EVAR versus standard EVAR for overall mortality showed that the information size has not been reached and the meta-analysis result is inconclusive with the cumulative Z-curve crossing neither the conventional significance threshold nor the O'Brien–Fleming boundaries. More trials are needed to confidently conclude on potential effects of pre-emptive embolization on overall mortality.
Fig. 4Trial sequential analysis diagrams for (A) overall mortality, (B) type II endoleak, (C) type II endoleak-related reintervention, and (D) aneurysm sac expansion including both repeated non-superiority/non-inferiority and two-sided significance testing showing no significant benefit for overall mortality and type II endoleak-related reintervention of embolization endovascular aneurysm repair (EVAR) compared to standard EVAR (the cumulative Z score does not reach significance by crossing either the conventional boundary or the O’Brian-Fleming boundaries), and a significant benefit for type II endoleak and aneurysm sac expansion.
Fig. 4Trial sequential analysis diagrams for (A) overall mortality, (B) type II endoleak, (C) type II endoleak-related reintervention, and (D) aneurysm sac expansion including both repeated non-superiority/non-inferiority and two-sided significance testing showing no significant benefit for overall mortality and type II endoleak-related reintervention of embolization endovascular aneurysm repair (EVAR) compared to standard EVAR (the cumulative Z score does not reach significance by crossing either the conventional boundary or the O’Brian-Fleming boundaries), and a significant benefit for type II endoleak and aneurysm sac expansion.
For type II endoleak, trial sequential analysis showed a significant benefit of pre-emptive embolization; the cumulative Z-score reaches significance by crossing both the conventional boundary and the O'Brian–Fleming boundaries. It can be inferred that pre-emptive embolization is superior to standard EVAR without embolization for this outcome and no further trials are required.
The cumulative Z-curve for type II endoleak-related reintervention crosses neither the conventional significance boundaries nor the O'Brien–Fleming boundaries, and the information size has not been reached, meaning that the meta-analysis result is inconclusive and more trials are required to make inferences for this outcome. For aneurysm sac expansion, the information size has been reached and no more trials are required to confirm the benefit of pre-emptive embolization for this outcome.
Discussion
We found no significant difference for any of the primary outcomes, namely aneurysm-related mortality, overall mortality, and aneurysm rupture, between EVAR with pre-emptive embolization and standard EVAR without. No events were recorded for aneurysm-related mortality and aneurysm rupture, reflecting the underpowered trials and/or short follow-up. The risk of type II endoleak was reduced with pre-emptive embolization of the aneurysm sac or aortic side branches but such benefit did not translate into a reduction of type II endoleak-related reintervention. Pre-emptive embolization was not shown to prolong the procedural or fluoroscopy time and was found to be associated with a reduced risk of sac expansion. Trial sequential analyses confirmed a true positive finding for type II endoleak and aneurysm sac expansion but showed inconclusive results for overall mortality and type II endoleak-related reintervention. The absence of embolization-related complications and the high technical success rates reflect the safety of the procedure in the context of EVAR.
Type II endoleaks are not always benign. They have been reported to be associated with sac expansion and, commonly, require secondary interventions.
This is important, particularly in light of recent research, which has shown that not only sac expansion but also failure of the aneurysm sac to regress may result in a higher risk of death.
Deery et al. have shown that patients with type II endoleak have a relative risk of 3 for sac expansion and a relative risk of 0.2 for sac regression, which were independently associated with mortality.
Vascular Study Group of New England. Aneurysm sac expansion is independently associated with late mortality in patients treated with endovascular aneurysm repair.
All trials included in this review reported size-related outcomes. The trials found a reduction in both aneurysm sac volume and diameter in the embolization group. Such reductions in size did not translate in improvements in important clinical outcomes, such as aneurysm rupture and mortality.
Previous research has also shown that complications from type II endoleaks are significantly more common in persistent endoleaks or those that appear late.
Our analysis showed similar rates of type II endoleak early after the index EVAR but a significant reduction in the medium term.
Of the 3 previously published systematic reviews examining the effect of pre-emptive embolization in EVAR, only one distinguishes between early and late type II endoleaks.
Effectiveness of collateral arteries embolization before endovascular aneurysm repair to prevent type II endoleaks: a systematic review and meta-analysis.
These reviews included mainly observational studies, which contaminate the results because of selection bias and limit their applicability. The review of Yu et al.
Effectiveness of collateral arteries embolization before endovascular aneurysm repair to prevent type II endoleaks: a systematic review and meta-analysis.
Our results are in accordance with those of the previous studies.
The certainty of evidence was judged to be very low for the critical outcomes, mainly due to limited data and high risk of bias in the trials. Similarly, the level of evidence was judged to be very low for all secondary outcomes, except for type II endoleak, for which the level of evidence was low. Rates of secondary interventions for type II endoleak varied across the studies, which may reflect different indications and thresholds for treatment. Samura et al.
did not undertake reinterventions for type II endoleak in any of the trial participants, although the rate of sac expansion was significantly higher in the control group. Fabre et al.
Our findings should be viewed and interpreted in the context of limitations. Only patients at high risk for type II endoleak were eligible for inclusion in 3 of the trials, which may limit the external validity and applicability of our findings to the general EVAR population. The meta-analysis population and the number of events was low resulting in imprecision and downgrading the certainty of evidence. No events were recorded for the primary outcomes, which indicates that the trials are underpowered. The optimal information size was reached for none of the outcomes except for sac expansion, and the CI around both relative and absolute estimates of effect include both appreciable benefit and appreciable harm. Furthermore, outcome reporting was not consistent across the trials not allowing inclusion in statistical comparisons. Considerable heterogeneity between the trials was noted; plausible explanations include different eligibility criteria for participant enrollment, different definitions (e.g., sac expansion), and different indications and thresholds for secondary interventions. A limitation of the review process was that the trial authors were not contacted for missing data.
Conclusion
The evidence base on potential benefits of pre-emptive embolization as an adjunct to EVAR is limited. Available data suggest that such treatment may not confer a survival advantage compared to standard EVAR without aneurysms sac or aortic side branch embolization. Although pre-emptive embolization may reduce the risk of type II endoleak in the medium term, such benefit is not translated into a reduction of reintervention, aneurysm rupture, or aneurysm-related mortality. The optimal information size has not been reached, and underpowered studies may explain the absence of tangible benefits. None of the trials investigated patient-reported outcomes. Trial sequential analyses confirmed the meta-analysis result is inconclusive for critical outcomes. Further large studies with longer follow-up are required to provide more information and make inferences about potential benefits of pre-emptive embolization in EVAR.
Editor's Choice - European Society for Vascular Surgery (ESVS) 2019 clinical practice guidelines on the management of abdominal aorto-iliac artery aneurysms.
A meta-analysis of translumbar embolization versus transarterial embolization for type II endoleak after endovascular repair of abdominal aortic aneurysm.
Vascular Study Group of New England. Aneurysm sac expansion is independently associated with late mortality in patients treated with endovascular aneurysm repair.
Effectiveness of collateral arteries embolization before endovascular aneurysm repair to prevent type II endoleaks: a systematic review and meta-analysis.
Support: No financial support was obtained for the conduct of this review.
Competing Interests: The review authors have no competing interests to disclose or any relationships that could be perceived as conflict of interest for the conduct of this review.
Availability of Data, Code, and Other Materials: A list of studies that were excluded from this review with reasons, template data collection forms, data extracted from included studies, data used for all analyses, and analytical code can be obtained from the corresponding author upon request. Such data are not publicly available.
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