A Core Outcome Set for Intact Abdominal Aortic Aneurysm Repair.

OBJECTIVE: Technology and advances in clinical care have changed the management of abdominal aortic aneurysms (AAAs) but the clinical effectiveness of continuing advances needs to be assessed. To facilitate rapid synthesis of new evidence and improve stakeholder representation, including patients, the concept of core outcome sets has been developed. Core outcome sets, reflecting the needs of all stakeholders, have been established across several surgical specialties. This study aimed to develop an international core outcome set for intact AAA repair. METHODS: Following COMET methodology, potential outcomes were identified from a systematic review of published outcomes and focus groups involving patients, carers, and nurses. A 38 question Delphi consensus survey in lay language was developed (with translation to local languages); this included 35 themes identified from the findings of the systematic review and three themes from the focus groups. All three of the themes identified by the focus groups (cognitive, physical, and social functioning) can be evaluated from quality of life instruments, with overall quality of life being identified from the systematic review. The survey was completed by patients, carers or family members, vascular nurses, vascular surgeons, trainees, interventional radiologists, anaesthetists, and industry partners from six European countries. After two rounds of the survey, the top outcomes were discussed at a face to face multistakeholder consensus meeting. RESULTS: The 38 item questionnaire was amended after piloting among all stakeholder groups. After the first round of the Delphi survey (98 respondents), 15 questions were eliminated and 11 further questions were eliminated after round two (90 respondents). This left two outcome questions for discussion at the consensus meeting, where the top six outcomes were unanimously endorsed: mortality at 30 days (or in hospital if longer), secondary AAA rupture, overall quality of life and retention of cognitive functioning after recovery, 5 year survival, and continued sac growth. CONCLUSION: Six core outcomes are recommended for use as a minimum framework in all future studies and registries of intact open and endovascular AAA repair. Further work to select instruments for quality of life and define instruments for cognitive functioning is needed.

Editor's Choice -- European Society for Vascular Surgery (ESVS) 2024 Clinical Practice Guidelines on the Management of Abdominal Aorto-Iliac Artery Aneurysms.

OBJECTIVE: The European Society for Vascular Surgery (ESVS) has developed clinical practice guidelines for the care of patients with aneurysms of the abdominal aorta and iliac arteries in succession to the 2011 and 2019 versions, with the aim of assisting physicians and patients in selecting the best management strategy. METHODS: The guideline is based on scientific evidence completed with expert opinion on the matter. By summarising and evaluating the best available evidence, recommendations for the evaluation and treatment of patients have been formulated. The recommendations are graded according to a modified European Society of Cardiology grading system, where the strength (class) of each recommendation is graded from I to III and the letters A to C mark the level of evidence. RESULTS: A total of 160 recommendations have been issued on the following topics: Service standards, including surgical volume and training; Epidemiology, diagnosis, and screening; Management of patients with small abdominal aortic aneurysm (AAA), including surveillance, cardiovascular risk reduction, and indication for repair; Elective AAA repair, including operative risk assessment, open and endovascular repair, and early complications; Ruptured and symptomatic AAA, including peri-operative management, such as permissive hypotension and use of aortic occlusion balloon, open and endovascular repair, and early complications, such as abdominal compartment syndrome and colonic ischaemia; Long term outcome and follow up after AAA repair, including graft infection, endoleaks and follow up routines; Management of complex AAA, including open and endovascular repair; Management of iliac artery aneurysm, including indication for repair and open and endovascular repair; and Miscellaneous aortic problems, including mycotic, inflammatory, and saccular aortic aneurysm. In addition, Shared decision making is being addressed, with supporting information for patients, and Unresolved issues are discussed. CONCLUSION: The ESVS Clinical Practice Guidelines provide the most comprehensive, up to date, and unbiased advice to clinicians and patients on the management of abdominal aorto-iliac artery aneurysms.

Assessment of Subclinical Atherosclerosis in Asymptomatic People In Vivo: Measurements Suitable for Biomarker and Mendelian Randomization Studies.

BACKGROUND: One strategy to reduce the burden of cardiovascular disease is the early detection and treatment of atherosclerosis. This has led to significant interest in studies of subclinical atherosclerosis, using different phenotypes, not all of which are accurate reflections of the presence of asymptomatic atherosclerotic plaques. The aim of part 2 of this series is to provide a review of the existing literature on purported measures of subclinical disease and recommendations concerning which tests may be appropriate in the prevention of incident cardiovascular disease. METHODS: We conducted a critical review of measurements used to infer the presence of subclinical atherosclerosis in the major conduit arteries and focused on the predictive value of these tests for future cardiovascular events, independent of conventional cardiovascular risk factors, in asymptomatic people. The emphasis was on studies with >10 000 person-years of follow-up, with meta-analysis of results reporting adjusted hazard ratios (HRs) with 95% CIs. The arterial territories were limited to carotid, coronary, aorta, and lower limb arteries. RESULTS: In the carotid arteries, the presence of plaque (8 studies) was independently associated with future stroke (pooled HR, 1.89 [1.04-3.44]) and cardiac events (7 studies), with a pooled HR, 1.77 (1.19-2.62). Increased coronary artery calcium (5 studies) was associated with the risk of coronary heart disease events, pooled HR, 1.54 (1.07-2.07) and increasing severity of calcification (by Agaston score) was associated with escalation of risk (13 studies). An ankle/brachial index (ABI) of <0.9, the pooled HR for cardiovascular death from 7 studies was 2.01 (1.43-2.81). There were insufficient studies of either, thoracic or aortic calcium, aortic diameter, or femoral plaque to synthesize the data based on consistent reporting of these measures. CONCLUSIONS: The presence of carotid plaque, coronary artery calcium, or abnormal ankle pressures seems to be a valid indicator of the presence of subclinical atherosclerosis and may be considered for use in biomarker, Mendelian randomization and similar studies.

Pathogenesis and management of abdominal aortic aneurysm.

Abdominal aortic aneurysm (AAA) causes ∼170 000 deaths annually worldwide. Most guidelines recommend asymptomatic small AAAs (30 to <50 mm in women; 30 to <55 mm in men) are monitored by imaging and large asymptomatic, symptomatic, and ruptured AAAs are considered for surgical repair. Advances in AAA repair techniques have occurred, but a remaining priority is therapies to limit AAA growth and rupture. This review outlines research on AAA pathogenesis and therapies to limit AAA growth. Genome-wide association studies have identified novel drug targets, e.g. interleukin-6 blockade. Mendelian randomization analyses suggest that treatments to reduce low-density lipoprotein cholesterol such as proprotein convertase subtilisin/kexin type 9 inhibitors and smoking reduction or cessation are also treatment targets. Thirteen placebo-controlled randomized trials have tested whether a range of antibiotics, blood pressure-lowering drugs, a mast cell stabilizer, an anti-platelet drug, or fenofibrate slow AAA growth. None of these trials have shown convincing evidence of drug efficacy and have been limited by small sample sizes, limited drug adherence, poor participant retention, and over-optimistic AAA growth reduction targets. Data from some large observational cohorts suggest that blood pressure reduction, particularly by angiotensin-converting enzyme inhibitors, could limit aneurysm rupture, but this has not been evaluated in randomized trials. Some observational studies suggest metformin may limit AAA growth, and this is currently being tested in randomized trials. In conclusion, no drug therapy has been shown to convincingly limit AAA growth in randomized controlled trials. Further large prospective studies on other targets are needed.

Sex-specific differences in the standard of care for infrarenal abdominal aortic aneurysm repair, and risk of major adverse cardiovascular events and death.

BACKGROUND: This study investigated whether sex-specific differences in preoperative/perioperative standard of care (SOC) account for disparity in outcomes after elective infrarenal abdominal aortic aneurysm repair. METHODS: This was a retrospective cohort study of elective infrarenal abdominal aortic aneurysm repairs (2013-2020) using depersonalized patient-level National Vascular Registry data. SOC was defined for waiting times, preoperative assessment (multidisciplinary/anaesthetic review), cardiovascular risk prevention, and perioperative medication. The primary outcome was major cardiovascular event and/or death (MACED). RESULTS: Some 21 810 patients with an infrarenal abdominal aortic aneurysm were included, 2380 women and 19 430 men. Women less often underwent aneurysm repair within SOC waiting times (51.5 versus 59.3 per cent; P < 0.001), but were equally likely to receive preoperative assessment (72.1 versus 72.5 per cent; P = 0.742). Women were less likely to receive secondary prevention for known cardiac disease (34.9 versus 39.6 per cent; P = 0.015), but more often met overall cardiovascular risk prevention standards (52.1 versus 47.3 per cent; P < 0.001). Women were at greater risk of MACED (open: 12.0 versus 8.9 per cent, P < 0.001; endovascular: 4.9 versus 2.9 per cent, P < 0.001; risk-adjusted OR 1.33, 95 per cent c.i. 1.12 to 1.59). A significant reduction in the odds of MACED was associated with preoperative assessment (OR 0.86, 0.75 to 0.98) and SOC waiting times (OR 0.78, 0.69 to 0.87). There was insufficient evidence to confirm a significant sex-specific difference in the effect of SOC preoperative assessment (women: OR 0.69, 0.50 to 0.97; men: OR 0.89, 0.77 to 1.03; interaction P = 0.170) or SOC waiting times (women: OR 0.84, 0.62 to 1.16; men: OR 0.76, 0.67 to 0.87; interaction P = 0.570) on the risk of MACED. CONCLUSION: SOC waiting times and preoperative assessment were not met for both sexes, which was associated with an increased risk of MACED. Sex-specific differences in SOC attenuated but did not fully account for the increased risk of MACED in women.

Shared Decision Making and the Management of Intact Abdominal Aortic Aneurysm: A Scoping Review of the Literature.

OBJECTIVE: The aim of this study was to summarise the current knowledge of shared decision making (SDM) in patients facing a treatment decision about an intact abdominal aortic aneurysm (AAA), and to identify where further evidence is needed. DATA SOURCES: MEDLINE, Embase, and the Cochrane Library were searched on 18 July 2021. An updated search was run on 31 May 2022 for relevant studies published from 1 January 2000 to 31 May 2022. REVIEW METHODS: This scoping review was undertaken in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines following a pre-defined protocol, retrieving studies reporting on aspects of SDM in those with intact AAAs. Qualitative synthesis of the articles was performed, and the results grouped according to theme. RESULTS: Fifteen articles reporting on a total of 1 344 participants (age range 62-74 years) from hospital vascular surgery clinics with intact AAAs were included. Studies were observational (n = 9), non-randomised studies of an intervention (n = 3), and randomised clinical trials (n = 3). The first theme was the preferences and practice of SDM. The proportion of patients preferring SDM ranged from 58% to 95% (three studies), although objective rating of SDM practice was consistently < 50% (three studies). Clinician training improved SDM practice. The second theme was poor provision of information. Fewer than half of patients (0 - 46%) surveyed were informed about all available treatment options (three studies). Publicly available information sources were rated as poor. The third theme concerned the utility of decision making support tools (DSTs). Two randomised trials demonstrated that the provision of DSTs improves patient knowledge and agreement between patient preference and repair type received but not objective measures of SDM for patients with AAAs. CONCLUSION: SDM for patients with an intact AAA appears to be in its infancy. Most patients with an AAA want SDM, but this is not commonly applied. Most patients with an AAA do not receive adequate information for SDM, although the use of bespoke DSTs leaves patients better informed to facilitate SDM.

Developing Core Outcome Sets for Vascular Conditions Across Europe, Not as Easy as It Sounds.

Introduction: Most of the outcomes reported in the literature have been chosen by doctors, constituting "traditional" outcome measures such as mortality and re-intervention. Some of the key outcome measures important to patients, families, health providers and other stakeholders may have been overlooked. Core outcome sets, consisting of 6-15 outcomes, can improve representation of all key stakeholders, standardise outcome reporting, and improve future ability to pool results. The aim of this study was to outline the methods and challenges of conducting European core outcome sets. Report: As an overview, development of core outcome sets follows a multistep iterative process: (1) Systematic review of the literature summarising existing outcome measures, (2) Focus Group meeting with patients and other stakeholders to establish missing outcome measures, (3) Development and piloting of Delphi survey, (4) Delphi consensus study for prioritisation of outcomes and establishing consensus, and (5) European consensus meeting to produce a core outcome set. The challenges include the varying ethical requirements for survey work across Europe and translation for surveys and consensus meetings. Discussion: There is an increasing need for core outcome sets to complement clinical practice guidelines. As a European vascular community we need to produce these through collaborative efforts. Unfortunately, there are considerable barriers to doing so - the time and energy required to set up a core outcome study is not dissimilar to that of a multicentre randomised trial. Currently only one core outcome set exists for vascular surgery, for critical limb ischaemia, but this was developed in a single country.

Systematic Reviews of the Literature Are Not Always Either Useful Or the Best Way To Add To Science.

Systematic reviews are becoming more popular as a way of doing research; however, not all systematic reviews are clinically useful and sometimes another type of review (scoping, topical, or critical) would be of greater value to the clinical and scientific community. The different types of review and their use are described, illustrated by examples relevant to vascular surgery.

Low Shear Stress at Baseline Predicts Expansion and Aneurysm-Related Events in Patients With Abdominal Aortic Aneurysm.

BACKGROUND: Low shear stress has been implicated in abdominal aortic aneurysm (AAA) expansion and clinical events. We tested the hypothesis that low shear stress in AAA at baseline is a marker of expansion rate and future aneurysm-related events. METHODS: Patients were imaged with computed tomography angiography at baseline and followed up every 6 months >24 months with ultrasound measurements of maximum diameter. From baseline computed tomography angiography, we reconstructed 3-dimensional models for automated computational fluid dynamics simulations and computed luminal shear stress. The primary composite end point was aneurysm repair and/or rupture, and the secondary end point was aneurysm expansion rate. RESULTS: We included 295 patients with median AAA diameter of 49 mm (interquartile range, 43-54 mm) and median follow-up of 914 (interquartile range, 670-1112) days. There were 114 (39%) aneurysm-related events, with 13 AAA ruptures and 98 repairs (one rupture was repaired). Patients with low shear stress (<0.4 Pa) experienced a higher number of aneurysm-related events (44%) compared with medium (0.4-0.6 Pa; 27%) and high (>0.6 Pa; 29%) shear stress groups (P=0.010). This association was independent of known risk factors (adjusted hazard ratio, 1.72 [95% CI, 1.08-2.73]; P=0.023). Low shear stress was also independently associated with AAA expansion rate (ß=+0.28 mm/y [95% CI, 0.02-0.53]; P=0.037). CONCLUSIONS: We show for the first time that low shear stress (<0.4 Pa) at baseline is associated with both AAA expansion and future aneurysm-related events. Aneurysms within the lowest tertile of shear stress, versus those with higher shear stress, were more likely to rupture or reach thresholds for elective repair. Larger prospective validation trials are needed to confirm these findings and translate them into clinical management.

Editor's Choice - Systematic Review and Meta-Analysis of Sex Specific Differences in Adverse Events After Open and Endovascular Intact Abdominal Aortic Aneurysm Repair: Consistently Worse Outcomes for Women.

OBJECTIVE: Previously, reports have shown that women experience a higher mortality rate than men after elective open (OAR) and endovascular (EVAR) repair of abdominal aortic aneurysm (AAA). With recent improvements in overall AAA repair outcomes, this study aimed to identify whether sex specific disparity has been ameliorated by modern practice, and to define sex specific differences in peri- and post-operative complications and pre-operative status; factors which may contribute to poor outcome. METHODS: This was a systematic review, meta-analysis, and meta-regression of sex specific differences in 30 day mortality and complications conducted according to PRISMA guidance (Prospero registration CRD42020176398). Papers with ≥ 50 women, reporting sex specific outcomes, following intact primary AAA repair, from 2000 to 2020 worldwide were included; with separate analyses for EVAR and OAR. Data sources were Medline, Embase, and CENTRAL databases 2005 - 2020 searched using ProQuest Dialog. RESULTS: Twenty-six studies (371 215 men, 65 465 women) were included. Meta-analysis and meta-regression indicated that sex specific odds ratios (ORs) for 30 day mortality were unchanged from 2000 to 2020. Mortality risk was higher in women for OAR and more so for EVAR (OR [95% CI] 1.49 [1.37 - 1.61]; 1.86 [1.59 - 2.17], respectively) and this remained following multivariable risk adjustment. Transfusion, pulmonary complications, and bowel ischaemia were more common in women after OAR and EVAR (OAR: ORs 1.81 [1.60 - 2.04], 1.40 [1.28 - 1.53], 1.54 [1.36 - 1.75]; EVAR: ORs 2.18 [2.08 - 2.29] 1.44 [1.17 - 1.77], 1.99 [1.51 - 2.62], respectively). Arterial injury, limb ischaemia, renal and cardiac complications were more common in women after EVAR (ORs 3.02 [1.62 - 5.65], 2.13 [1.48 - 3.06], 1.46 [1.22 - 1.72] and 1.19 [1.03 - 1.37], respectively); the latter was associated with greater mortality risk on meta-regression. CONCLUSION: Increased mortality risk for women following AAA repair remains. Women had a higher incidence of transfusion, pulmonary and bowel complications after EVAR and OAR. Higher mortality risk ratios for EVAR may result from cardiac complications, additional arterial injury, and embolisation, leading to renal and limb ischaemia. These findings indicate possible causes for observed outcome disparities and targets for quality improvement.

Towards a Core Outcome Set for Abdominal Aortic Aneurysm: Systematic Review of Outcomes Reported Following Intact and Ruptured Abdominal Aortic Aneurysm Repair.

OBJECTIVE: To encompass the needs of all stakeholders and allow effective data synthesis from trials, registries, and other studies; a core outcome set for infrarenal abdominal aortic aneurysm (AAA) repair is needed. In this first stage, the aim was to report the range, frequency, and time of pre-specified outcomes reported following AAA repair. DATA SOURCES: Medline, Embase, and CENTRAL databases 2010 - 2019 were searched using ProQuest Dialog™. REVIEW METHODS: The systematic review was reported to Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines (PRISMA), PROSPERO registration CRD42019130119. Outcomes were coded using Core Outcome Measures in Effectiveness Trials (COMET) taxonomy and presented separately for intact and rupture repairs, endovascular aneurysm repair (EVAR) and open repair, and time from repair (acute < 90 days vs. ≥ 1 year) (COMET Initiative 1582). RESULTS: For intact AAA and rupture repair, a total of 231 and 70 reports with 589 255 and 177 465 patients respectively were included: only 98 and 19 respectively provided ≥ 1 year outcomes. Most studies were retrospective, with 13 randomised trials of intact AAA repair and five randomised trials of ruptured AAA repair. For intact AAA, the most common pre-specified COMET taxonomy outcomes were mortality (181), vascular complications (137), and re-intervention (52). EVAR studies dominated the vascular outcomes in acute and later time periods: excluding 47 reports from device registries, reduced vascular outcomes to 83. For ruptured AAA, the three most common outcomes were mortality (64), vascular (11), and hospital stay (10). The range of outcomes reported was wide with functioning outcomes reported from most randomised trials but few retrospective studies. CONCLUSION: This review identifies the paucity of long term data and the disproportionate attention paid to vascular complications vs. patient functioning outcomes, this skew being accentuated by reporting from EVAR device registries. These data will inform focus groups, prior to a pan-European Delphi consensus, involving clinicians, patients, carers and providers, for developing core outcomes for repair of intact and ruptured AAA.

Surgery for small asymptomatic abdominal aortic aneurysms.

BACKGROUND: An abdominal aortic aneurysm (AAA) is an abnormal ballooning of the major abdominal artery. Some AAAs present as emergencies and require surgery; others remain asymptomatic. Treatment of asymptomatic AAAs depends on many factors, but the size of the aneurysm is important, as risk of rupture increases with aneurysm size. Large asymptomatic AAAs (greater than 5.5 cm in diameter) are usually repaired surgically; very small AAAs (less than 4.0 cm diameter) are monitored with ultrasonography. Debate continues over the roles of early repair versus surveillance with repair on subsequent enlargement in people with asymptomatic AAAs of 4.0 cm to 5.5 cm diameter. This is the fourth update of the review first published in 1999. OBJECTIVES: To compare mortality and costs, as well as quality of life and aneurysm rupture as secondary outcomes, following early surgical repair versus routine ultrasound surveillance in people with asymptomatic AAAs between 4.0 cm and 5.5 cm in diameter. SEARCH METHODS: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, two other databases, and two trials registers to 10 July 2019. We handsearched conference proceedings and checked reference lists of relevant studies. SELECTION CRITERIA: We included randomised controlled trials where people with asymptomatic AAAs of 4.0 cm to 5.5 cm were randomly allocated to early repair or imaging-based surveillance at least every six months. Outcomes had to include mortality or survival. DATA COLLECTION AND ANALYSIS: Three review authors independently extracted data, which were cross-checked by other team members. Outcomes were mortality, costs, quality of life, and aneurysm rupture. For mortality, we estimated risk ratios (RR) (endovascular aneurysm repair only), hazard ratios (HR) (open repair only), and 95% confidence intervals (CI) based on Mantel-Haenszel Chi2 statistics at one and six years (open repair only) following randomisation. MAIN RESULTS: We found no new studies for this update. Four trials with 3314 participants fulfilled the inclusion criteria. Two trials compared early open repair with surveillance and two trials compared early endovascular repair (EVAR) with surveillance. We used GRADE to access the certainty of the evidence for mortality and cost, which ranged from high to low. We downgraded the certainty in the evidence from high to moderate and low due to risk of bias concerns and imprecision (some outcomes were only reported by one study). All four trials showed an early survival benefit in the surveillance group (due to 30-day operative mortality with repair) but no evidence of differences in long-term survival. One study compared early open repair with surveillance with an adjusted HR of 0.88 (95% CI 0.75 to 1.02, mean follow-up 10 years; HR 1.21, 95% CI 0.95 to 1.54, mean follow-up 4.9 years). Pooled analysis of participant-level data from the two trials comparing early open repair with surveillance (maximum follow-up seven to eight years) showed no evidence of a difference in survival (propensity score-adjusted HR 0.99, 95% CI 0.83 to 1.18; 2226 participants; high-certainty evidence). This lack of treatment effect did not vary to three years by AAA diameter (P = 0.39), participant age (P = 0.61), or for women (HR 0.84, 95% CI 0.62 to 1.11). Two studies compared EVAR with surveillance and there was no evidence of a survival benefit for early EVAR at 12 months (RR 1.92, 95% CI 0.73 to 5.06; 846 participants; low-certainty evidence). Two trials reported costs. The mean UK health service costs per participant over the first 18 months after randomisation were higher in the open repair surgery than the surveillance group (GBP 4978 in the repair group versus GBP 3914 in the surveillance group; mean difference (MD) GBP 1064, 95% CI 796 to 1332; 1090 participants; moderate-certainty evidence). There was a similar difference after 12 years. The mean USA hospital costs for participants at six months after randomisation were higher in the EVAR group than in the surveillance group (USD 33,471 with repair versus USD 5520 with surveillance; MD USD 27,951, 95% CI 25,156 to 30,746; 614 participants; low-certainty evidence). After four years, there was no evidence of a difference in total medical costs between groups (USD 48,669 with repair versus USD 46,112 with surveillance; MD USD 2557, 95% CI -8043 to 13,156; 614 participants; low-certainty evidence). All studies reported quality of life but used different assessment measurements and results were conflicting. All four studies reported aneurysm rupture. There were very few ruptures reported in the trials of EVAR versus surveillance up to three years. In the trials of open surgery versus surveillance, there were ruptures to at least six years and there were more ruptures in the surveillance group, but most of these ruptures occurred in aneurysms that had exceeded the threshold for surgical repair. AUTHORS' CONCLUSIONS: There was no evidence of an advantage to early repair for small AAA (4.0 cm to 5.5 cm), regardless of whether open repair or EVAR is used and, at least for open repair, regardless of patient age and AAA diameter. Thus, neither early open nor early EVAR of small AAAs is supported by currently available evidence. Long-term data from the two trials investigating EVAR are not available, so, we can only draw firm conclusions regarding outcomes after the first few years for open repair. Research regarding the risks related to and management of small AAAs in ethnic minorities and women is urgently needed, as data regarding these populations are lacking.