Optimizing Surveillance and Re-intervention Strategy Following Elective Endovascular Repair of Abdominal Aortic Aneurysms.

BACKGROUND: EVAR for abdominal aortic aneurysm has an initial survival advantage over OR, but more frequent complications increase costs and long-term aneurysm-related mortality. Randomized controlled trials of EVAR versus OR have shown EVAR is not cost-effective over a patient's lifetime. However, in the EVAR-1 trial, postoperative surveillance may have been sub-optimal, as the importance of sac growth as a predictor of graft failure was overlooked. METHODS: Real-world data informed a discrete event simulation model of postoperative outcomes following EVAR. Outcomes observed EVAR-1 were compared with those from 5 alternative postoperative surveillance and re-intervention strategies. Key events, quality-adjusted life years and costs were predicted. The impact of using complication and rupture rates from more recent devices, imaging and re-intervention methods was also explored. RESULTS: Compared with observed EVAR-1 outcomes, modeling full adherence to the EVAR-1 scan protocol reduced abdominal aortic aneurysm (AAA) deaths by 3% and increased elective re-interventions by 44%. European Society re-intervention guidelines provided the most clinically effective strategy, with an 8% reduction in AAA deaths, but a 52% increase in elective re-interventions. The cheapest and most cost-effective strategy used lifetime annual ultrasound in primary care with confirmatory computed tomography if necessary, and reduced AAA-related deaths by 5%. Using contemporary rates for complications and rupture did not alter these conclusions. CONCLUSIONS: All alternative strategies improved clinical benefits compared with the EVAR-1 trial. Further work is needed regarding the cost and accuracy of primary care ultrasound, and the potential impact of these strategies in the comparison with OR.

Silent Brain Infarction After Endovascular Arch Procedures: Preliminary Results from the STEP Registry.

OBJECTIVE: Few data exist concerning the rate of silent cerebral ischaemic events following endovascular treatment of the aortic arch. The objective of this work was to quantify these lesions using the STEP registry (NCT04489277). METHODS: This multicentre retrospective cohort study included consecutive patients treated with an aortic endoprosthesis deployed in Ishimaru zone 0-3 and brain diffusion weighted magnetic resonance imaging (DW-MRI) within seven days following the procedure. DW-MRI was performed to identify the location and number of new silent brain infarctions (SBI). All endografts were carbon dioxide flushed prior to implantation. RESULTS: The study population included 91 patients (mean age, 69 years; men, 64%) from two academic centres treated between September 2018 and January 2020. The procedure was elective in 71 patients (78%). The treatment was performed for a dissection, degenerative aneurysm, or other aortic disease in 44 (49%), 34 (37%), and 13 (14%) patients, respectively. Endografts were deployed in zone 0, 1, 2 or 3 in 23 (25%), 10 (11%), 47 (52%), and 11 (12%) patients, respectively. Endografts were branched (25%), fenestrated (17%), or tubular (58%). At 30 days, there were no deaths or clinical strokes. On cerebral DW-MRI, a total of 245 SBI were identified in 45 patients (50%). Lesions were in the left hemisphere in 63% of the patients (153/245), predominantly in the middle territory (94/245). Deployment in zone 0-1 (p = .026), placement of a branched or fenestrated endograft (p = .038), a proximal endoprosthesis diameter ≥ 40 mm (p = .038), and an urgent procedure (p = .005) were significantly associated with the presence of SBI on univariable analysis, while urgent procedure was found to be an independent predictor on multivariable analysis (binary logistic regression) (p = .002). CONCLUSION: SBI following endovascular repair of the aortic arch is frequent, although there were no clinical strokes. Innovative strategies to reduce the risk of embolisation need to be developed.

Endovascular Repair of Abdominal Aortic Aneurysm in Patients Physically Ineligible for Open Repair: Very Long-term Follow-up in the EVAR-2 Randomized Controlled Trial.

OBJECTIVE: The aim of the study was to compare long-term total and aneurysm-related mortality in physically frail patients with abdominal aortic aneurysm (AAA) randomized to either early endovascular aneurysm repair (EVAR) or no-intervention. SUMMARY BACKGROUND DATA: EVAR-2 remains the sole randomized trial to identify whether EVAR reduces mortality in patients physically ineligible for open repair. METHODS: Between September 1999 and August 2004, 404 patients from 33 centers in the United Kingdom aged ≥60 years with AAA >5.5 cm in diameter were randomized 1:1 using computer-generated sequences of randomly permuted blocks stratified by center to receive either EVAR (197) or no-intervention (207). The primary analysis compared total and aneurysm-related deaths in groups until June 30, 2015 (mean, 12.0 yrs; maximum 14.1 yrs). RESULTS: Mean follow-up until death or censoring was 4.2 years. There were 187 deaths (22.6 per 100 person-yrs) in the EVAR group and 194 (22.1 per 100 person-yrs) in the no-intervention group. By 12 years of follow-up the estimated survival was 5.3% [95% confidence interval (CI), 2.6-9.2] in the EVAR group and 8.5% (95% CI, 5.2-12.9) in the no-intervention group; there was no significant difference in life expectancy between the groups (both 4.2 yrs; P = 0.97). However, overall aneurysm-related mortality was significantly lower in the EVAR group [3.3 deaths per 100 person-yrs compared with 6.5 deaths per 100 person-yrs in the no-intervention group, adjusted hazard ratio 0.55 (95% CI, 0.34-0.91; P = 0.019)]. Patients surviving beyond 8 years were younger, with higher body mass index, estimated glomerular filtration rate, and forced expiratory volume in 1 second. CONCLUSIONS: EVAR does not increase overall life expectancy in patients ineligible for open repair, but can reduce aneurysm-related mortality.

Endovascular versus open repair of abdominal aortic aneurysm in 15-years' follow-up of the UK endovascular aneurysm repair trial 1 (EVAR trial 1): a randomised controlled trial.

BACKGROUND: Short-term survival benefits of endovascular aneurysm repair (EVAR) versus open repair of intact abdominal aortic aneurysms have been shown in randomised trials, but this early survival benefit is lost after a few years. We investigated whether EVAR had a long-term survival benefit compared with open repair. METHODS: We used data from the EVAR randomised controlled trial (EVAR trial 1), which enrolled 1252 patients from 37 centres in the UK between Sept 1, 1999, and Aug 31, 2004. Patients had to be aged 60 years or older, have aneurysms of at least 5·5 cm in diameter, and deemed suitable and fit for either EVAR or open repair. Eligible patients were randomly assigned (1:1) using computer-generated sequences of randomly permuted blocks stratified by centre to receive either EVAR (n=626) or open repair (n=626). Patients and treating clinicians were aware of group assignments, no masking was used. The primary analysis compared total and aneurysm-related deaths in groups until mid-2015 in the intention-to-treat population. This trial is registered at ISRCTN (ISRCTN55703451). FINDINGS: We recruited 1252 patients between Sept 1, 1999, and Aug 31, 2004. 25 patients (four for mortality outcome) were lost to follow-up by June 30, 2015. Over a mean of 12·7 years (SD 1·5; maximum 15·8 years) of follow-up, we recorded 9·3 deaths per 100 person-years in the EVAR group and 8·9 deaths per 100 person-years in the open-repair group (adjusted hazard ratio [HR] 1·11, 95% CI 0·97-1·27, p=0·14). At 0-6 months after randomisation, patients in the EVAR group had a lower mortality (adjusted HR 0·61, 95% CI 0·37-1·02 for total mortality; and 0·47, 0·23-0·93 for aneurysm-related mortality, p=0·031), but beyond 8 years of follow-up open-repair had a significantly lower mortality (adjusted HR 1·25, 95% CI 1·00-1·56, p=0·048 for total mortality; and 5·82, 1·64-20·65, p=0·0064 for aneurysm-related mortality). The increased aneurysm-related mortality in the EVAR group after 8 years was mainly attributable to secondary aneurysm sac rupture (13 deaths [7%] in EVAR vs two [1%] in open repair), with increased cancer mortality also observed in the EVAR group. INTERPRETATION: EVAR has an early survival benefit but an inferior late survival compared with open repair, which needs to be addressed by lifelong surveillance of EVAR and re-intervention if necessary. FUNDING: UK National Institute for Health Research, Camelia Botnar Arterial Research Foundation.

Endovascular versus open repair of abdominal aortic aneurysm.

BACKGROUND: Few data are available on the long-term outcome of endovascular repair of abdominal aortic aneurysm as compared with open repair. METHODS: From 1999 through 2004 at 37 hospitals in the United Kingdom, we randomly assigned 1252 patients with large abdominal aortic aneurysms (> or = 5.5 cm in diameter) to undergo either endovascular or open repair; 626 patients were assigned to each group. Patients were followed for rates of death, graft-related complications, reinterventions, and resource use until the end of 2009. Logistic regression and Cox regression were used to compare outcomes in the two groups. RESULTS: The 30-day operative mortality was 1.8% in the endovascular-repair group and 4.3% in the open-repair group (adjusted odds ratio for endovascular repair as compared with open repair, 0.39; 95% confidence interval [CI], 0.18 to 0.87; P=0.02). The endovascular-repair group had an early benefit with respect to aneurysm-related mortality, but the benefit was lost by the end of the study, at least partially because of fatal endograft ruptures (adjusted hazard ratio, 0.92; 95% CI, 0.57 to 1.49; P=0.73). By the end of follow-up, there was no significant difference between the two groups in the rate of death from any cause (adjusted hazard ratio, 1.03; 95% CI, 0.86 to 1.23; P=0.72). The rates of graft-related complications and reinterventions were higher with endovascular repair, and new complications occurred up to 8 years after randomization, contributing to higher overall costs. CONCLUSIONS: In this large, randomized trial, endovascular repair of abdominal aortic aneurysm was associated with a significantly lower operative mortality than open surgical repair. However, no differences were seen in total mortality or aneurysm-related mortality in the long term. Endovascular repair was associated with increased rates of graft-related complications and reinterventions and was more costly. (Current Controlled Trials number, ISRCTN55703451.)

Endovascular repair of aortic aneurysm in patients physically ineligible for open repair.

BACKGROUND: Endovascular repair of abdominal aortic aneurysm was originally developed for patients who were considered to be physically ineligible for open surgical repair. Data are lacking on the question of whether endovascular repair reduces the rate of death among these patients. METHODS: From 1999 through 2004 at 33 hospitals in the United Kingdom, we randomly assigned 404 patients with large abdominal aortic aneurysms (> or = 5.5 cm in diameter) who were considered to be physically ineligible for open repair to undergo either endovascular repair or no repair; 197 patients were assigned to undergo endovascular repair, and 207 were assigned to have no intervention. Patients were followed for rates of death, graft-related complications and reinterventions, and costs until the end of 2009. Cox regression was used to compare outcomes in the two groups. RESULTS: The 30-day operative mortality was 7.3% in the endovascular-repair group. The overall rate of aneurysm rupture in the no-intervention group was 12.4 (95% confidence interval [CI], 9.6 to 16.2) per 100 person-years. Aneurysm-related mortality was lower in the endovascular-repair group (adjusted hazard ratio, 0.53; 95% CI, 0.32 to 0.89; P=0.02). This advantage did not result in any benefit in terms of total mortality (adjusted hazard ratio, 0.99; 95% CI, 0.78 to 1.27; P=0.97). A total of 48% of patients who survived endovascular repair had graft-related complications, and 27% required reintervention within the first 6 years. During 8 years of follow-up, endovascular repair was considerably more expensive than no repair (cost difference, 9,826 pounds sterling [U.S. $14,867]; 95% CI, 7,638 to 12,013 [11,556 to 18,176]). CONCLUSIONS: In this randomized trial involving patients who were physically ineligible for open repair, endovascular repair of abdominal aortic aneurysm was associated with a significantly lower rate of aneurysm-related mortality than no repair. However, endovascular repair was not associated with a reduction in the rate of death from any cause. The rates of graft-related complications and reinterventions were higher with endovascular repair, and it was more costly. (Current Controlled Trials number, ISRCTN55703451.)

The influence of thrombus, calcification, angulation, and tortuosity of attachment sites on the time to the first graft-related complication after endovascular aneurysm repair.

PURPOSE: Endovascular aneurysm repair (EVAR) is associated with high graft-related complication rates during follow-up. Anatomical fit between patient and endograft could be an important factor for successful treatment. Aim was to assess whether extent of thrombus, calcification, angulation, and tortuosity are associated with occurrence of complications after EVAR. MATERIALS AND METHODS: Patients in either United Kingdom EVAR trial 1 or 2 were included if they had undergone EVAR within 6 months of randomization and had a preoperative computed tomography (CT) scan of adequate quality in the core laboratory. Three-dimensional CT imaging was used to assess extent of preoperative thrombus, calcification, angulation, and tortuosity in aneurysm neck and iliac segments. Cox regression modeling, adjusted for the variables tested and for known confounding variables, was used to investigate whether these factors were associated with increased rates of reported first complications. RESULTS: A total of 217 patients with 53 first graft-related complications were analyzed after a mean follow-up of 3.6 years. Adjusted hazard ratios (95% confidence intervals, P values) for complications per unit increase of variable were 0.96 (0.92-0.99, 0.018) for neck thrombus, 1.06 (1.00-1.12, 0.044) for neck calcification, 1.02 (1.00-1.05, 0.079) for neck angulation, 1.04 (1.01-1.06, 0.011) for common iliac thrombus, 0.96 (0.93-1.00, 0.033) for common iliac calcification, and 5.96 (1.53-23.28, 0.010) for common iliac tortuosity. CONCLUSION: Increased neck angulation and calcification and common iliac thrombus and tortuosity are associated with higher rates of graft-related complications after EVAR. Increased neck thrombus and common iliac calcification appear to protect against complications. Careful evaluation of these factors prior to EVAR might lead to lower complication rates.

Rate and predictability of graft rupture after endovascular and open abdominal aortic aneurysm repair: data from the EVAR Trials.

OBJECTIVE: To assess the rate and factors associated with rupture after endovascular aneurysm repair (EVAR) or open repair (OR) of abdominal aortic aneurysm. BACKGROUND: Graft rupture after EVAR has been reported, often preceded by graft-related complications. Graft rupture has also been reported after OR. METHODS: By July 2009, a total of 848 elective EVARs and 594 elective ORs were performed in the United Kingdom EVAR trials 1 and 2. Patients were followed up for complications, reinterventions, and rupture. The incidence of rupture was explored in relation to baseline anatomy and subsequent complications in a Cox regression analysis. RESULTS: There were no ruptures in the OR patients. A total of 27 ruptures occurred after EVAR during a mean follow-up of 4.8 years: crude rate = 0.7 [95% confidence interval (CI): 0.5-1.0] ruptures per 100 person-years. Eighteen patients (67%) died within 30 days of rupture. Five ruptures occurred in the first 30 postoperative days and 22 after that: crude rates of rupture = 7.2 (95% CI: 3.0-17.4) and 0.6 (95% CI: 0.4-0.9) per 100 person-years, respectively. Previous complications (endoleak type 1, type 2 with sac expansion, type 3, migration or kinking) increased the risk of rupture, adjusted hazard ratio 8.83 (95% CI 3.76-20.76), P < 0.0001. CONCLUSIONS: There were no ruptures after OR and a low rate after EVAR. Mortality after graft rupture is high and previous serious complications are significantly associated with the risk of rupture. Few ruptures after EVAR seem to be spontaneous without complications identified during optimal surveillance.

Renal function and abdominal aortic aneurysm (AAA): the impact of different management strategies on long-term renal function in the UK EndoVascular Aneurysm Repair (EVAR) Trials.

OBJECTIVE: To investigate the impact of different management policies on renal function in patients with abdominal aortic aneurysm. SUMMARY BACKGROUND DATA: Limited longitudinal data exist on alterations in renal function in patients with abdominal aortic aneurysm. Escalating use of endovascular aneurysm repair (EVAR) with increased use of intensive imaging and contrast agents may have a deleterious effect on renal function. METHODS: Multilevel modeling of estimated Glomerular Filtration Rate (eGFR), measured annually over an average of 3.6 years, was performed on 1194 patients enrolled in the randomized EVAR trials to compare renal function in patients managed with open or endovascular repair or no intervention and investigate, which factors were associated with fast renal decline. RESULTS: For EVAR trial 1, the mean (SD) rate of change in eGFR was -1.13 (1.43) and -1.00 (1.43) mL/min/1.73 m per year for the EVAR and open repair groups, respectively, but this difference was not statistically significant (P=0.208). For EVAR trial 2, the mean (SD) rate of change in eGFR was -0.98 (1.49) and -0.76 (1.30) mL/min/1.73 m per year for the EVAR and no intervention groups, respectively (P=0.087). Faster rates of renal function decline were significantly associated with larger aortic neck diameters (P=0.003) and onset of graft-related complications after EVAR (P=0.001). CONCLUSIONS: In these patients deterioration in renal function was slow, with little evidence to suggest any long-term difference between treatment with EVAR or open repair in fit patients or between EVAR and no intervention in unfit patients. Graft complications and larger neck diameters appear to be associated with faster renal function decline.

Evaluation and stages of surgical innovations.

Surgical innovation is an important part of surgical practice. Its assessment is complex because of idiosyncrasies related to surgical practice, but necessary so that introduction and adoption of surgical innovations can derive from evidence-based principles rather than trial and error. A regulatory framework is also desirable to protect patients against the potential harms of any novel procedure. In this first of three Series papers on surgical innovation and evaluation, we propose a five-stage paradigm to describe the development of innovative surgical procedures.

No surgical innovation without evaluation: the IDEAL recommendations.

Surgery and other invasive therapies are complex interventions, the assessment of which is challenged by factors that depend on operator, team, and setting, such as learning curves, quality variations, and perception of equipoise. We propose recommendations for the assessment of surgery based on a five-stage description of the surgical development process. We also encourage the widespread use of prospective databases and registries. Reports of new techniques should be registered as a professional duty, anonymously if necessary when outcomes are adverse. Case series studies should be replaced by prospective development studies for early technical modifications and by prospective research databases for later pre-trial evaluation. Protocols for these studies should be registered publicly. Statistical process control techniques can be useful in both early and late assessment. Randomised trials should be used whenever possible to investigate efficacy, but adequate pre-trial data are essential to allow power calculations, clarify the definition and indications of the intervention, and develop quality measures. Difficulties in doing randomised clinical trials should be addressed by measures to evaluate learning curves and alleviate equipoise problems. Alternative prospective designs, such as interrupted time series studies, should be used when randomised trials are not feasible. Established procedures should be monitored with prospective databases to analyse outcome variations and to identify late and rare events. Achievement of improved design, conduct, and reporting of surgical research will need concerted action by editors, funders of health care and research, regulatory bodies, and professional societies.

Challenges in evaluating surgical innovation.

Research on surgical interventions is associated with several methodological and practical challenges of which few, if any, apply only to surgery. However, surgical evaluation is especially demanding because many of these challenges coincide. In this report, the second of three on surgical innovation and evaluation, we discuss obstacles related to the study design of randomised controlled trials and non-randomised studies assessing surgical interventions. We also describe the issues related to the nature of surgical procedures-for example, their complexity, surgeon-related factors, and the range of outcomes. Although difficult, surgical evaluation is achievable and necessary. Solutions tailored to surgical research and a framework for generating evidence on which to base surgical practice are essential.

Use of angiotensin converting enzyme inhibitors is associated with increased growth rate of abdominal aortic aneurysms.

OBJECTIVES: To evaluate whether either angiotensin converting enzyme (ACE) inhibitors or other classes of antihypertensive drug attenuate or increase growth rates of small infrarenal abdominal aortic aneurysms. METHODS: Prospective cohort study of 1701 patients enrolled in the UK Small Aneurysm Trial or associated study at 93 hospitals between 1991 and 1995 and who had at least two ultrasound measurements of aneurysm diameter and baseline drug prescription data recorded. Abdominal aortic aneurysm diameter was measured in the anterior-posterior plane using ultrasound. The mean growth rate was estimated through a mixed-effects linear growth model. RESULTS: Mean aneurysm growth rate in 169 patients taking ACE inhibitors at baseline was 3.33 mm/y vs 2.77 mm/y in the remaining 1532 patients, P = .009. The significance of this finding did not alter after adjustment for known confounders. The prescription of any antihypertensive agent and other specific classes of antihypertensive drugs were not found to be associated with aneurysm growth rate. CONCLUSION: These results show that patients taking ACE inhibitors have faster aneurysm growth and are in conflict with the observation from a large Canadian data-base that aneurysm patients taking ACE inhibitors are less likely to present with aneurysm rupture. There is an urgent need for a randomized trial to assess whether ACE inhibitors are beneficial or harmful to patients with aneurysms below the threshold size for surgical intervention.

The genetics of abdominal aortic aneurysms: a comprehensive meta-analysis involving eight candidate genes in over 16,700 patients.

Abdominal aortic aneurysms (AAAs) are thought to be multifactorial in etiology. A variety of susceptibility genes have been associated, but definitive conclusions have been difficult to draw and are partly hampered by the small number of patients in each study. We undertook a comprehensive meta-analysis on any gene that was investigated in a case-control model of AAA. A comprehensive, genetic meta-analysis of all genes investigated by using an allelic-association, case-control model in AAA was conducted. Electronic databases were searched through July 2009 for any candidate gene in AAA. Odds ratio (OR) and 95% confidence intervals (CIs) were determined for each gene-disease association by using fixed- and random-effect models. Twenty studies in 7 candidate genes were analysed among 16,748 individuals (i.e., 7891 patients and 8857 controls). Of the 8 genes studied, 5 genes were associated with AAA. The angiotensin-1 converting enzyme (ACE) insertion/deletion polymorphism (I/D) showed a significant association in both a dominant model (OR, 1.35; 95% CI, 1.17 to 1.56; P < 0.0001) and a recessive model (OR 1.24; 95% CI, 1.08 to 1.42; P < 0.00001). The pooled ORs for the C677T variant of 5,10-methyltetrahydrofolate reductase (MTHFR) were 1.34 (95% CI, 1.08 to 1.65; P = 0.007) for the dominant model and 1.16 (95% CI, 0.81 to 1.67; P = 0.41) for a recessive model. There was also significance in the dominant model of the angiotensin-1 receptor polymorphism (AT1R) A1166C (OR, 1.94; 95% CI, 1.66 to 2.28; P < 0.00001) and in the dominant (95% CI, 1.18 to 2.11; P = 0.002) and recessive (OR, 1.51; 95% CI, 1.13 to 2.02; P = 0.006) models of the interleukin-10 1082 polymorphism. The MMP-3 nt-1612 polymorphism was also significant in the dominant (OR, 1.4; 95% CI, 1.12 to 1.76; P = 0.003) and recessive (OR 1.3; 95% CI, 1.05 to 1.61; P = 0.02) models. In conclusion, there is a genetic basis to sporadic aortic aneurysms. Patients with the ACE/D and MTHFR/677T, AT1R/C, IL-10/A, and MMP-3 nt-1612 polymorphisms are at an increased risk of developing this condition.

Fit patients with small abdominal aortic aneurysms (AAAs) do not benefit from early intervention.

OBJECTIVES: The UK Small Aneurysm Trial (UKSAT) and the American Aneurysm Detection and Management (ADAM) trial both concluded that early elective open surgery does not confer any late survival advantage in patients with small abdominal aortic aneurysm (AAA) with diameter 4.0 to 5.5 cm. However, two trials of endovascular aneurysm repair in small AAA have started based upon speculation that a sub-group of particularly fit patients, with low operative mortality, may benefit from early intervention. Here we investigate whether the fittest patients from the UKSAT might have benefited from early intervention. METHODS: A total of 1090 patients randomized into the UKSAT between 1991 and 1995 were followed for an average of 12 years for mortality. Baseline data were used to calculate the Customized Probability Index (CPI), a validated prognostic risk score for operative mortality after elective open aneurysm repair that assigns risk points for history of cardiac, pulmonary, and renal disease and subtracts risk points for use of statins and beta-blockers. Cox regression was used to assess any differences in all-cause or aneurysm-related mortality between policies of early surgery or surveillance across the fitness spectrum. Tests for interaction used CPI scores as a continuous variable but patients also were stratified into tertile groups for descriptive purposes. Hazard ratios were adjusted for age, gender, and aneurysm diameter. RESULTS: A total of 714 deaths (95 aneurysm-related) occurred in 8485 person-years (number of patients multiplied by average years of conditional follow-up). The mean (standard deviation [SD]) CPI score was 8.1 (9.9) with similar scores between randomized groups. The tertile groups had mean (SD) scores of -1.8 (3.7) for the 389 fittest patients, 8.8 (3.3) for the 438 moderately fit, 21.4 (6.6) for the 261 least fit with missing scores in 2 patients. The tests for interaction were non-significant for both all-cause (P = .176) and aneurysm-related mortality (.178). However, for the least fit patients a survival advantage was seen in the early surgery group; adjusted hazard ratios 0.73 (95% confidence interval [CI] 0.56-0.96) and 0.46 (95% CI 0.22-0.98) for all-cause and aneurysm-related mortality respectively. CONCLUSION: Early elective surgery did not confer any survival benefit in the fittest patients. On the contrary, the possibility of a survival benefit from early intervention in patients of poor fitness merits further investigation through meta-analysis or validation in other prospective studies.

The UK EndoVascular Aneurysm Repair (EVAR) randomised controlled trials: long-term follow-up and cost-effectiveness analysis.

BACKGROUND: Short-term survival benefits of endovascular aneurysm repair (EVAR) compared with open repair (OR) of intact abdominal aortic aneurysms have been shown in randomised trials, but this early survival benefit is soon lost. Survival benefit of EVAR was unclear at follow-up to 10 years. OBJECTIVE: To assess the long-term efficacy of EVAR against OR in patients deemed fit and suitable for both procedures (EVAR trial 1; EVAR-1); and against no intervention in patients unfit for OR (EVAR trial 2; EVAR-2). To appraise the long-term significance of type II endoleak and define criteria for intervention. DESIGN: Two national, multicentre randomised controlled trials: EVAR-1 and EVAR-2. SETTING: Patients were recruited from 37 hospitals in the UK between 1 September 1999 and 31 August 2004. PARTICIPANTS: Men and women aged ≥ 60 years with an aneurysm of ≥ 5.5 cm (as identified by computed tomography scanning), anatomically suitable and fit for OR were randomly assigned 1 : 1 to either EVAR (n = 626) or OR (n = 626) in EVAR-1 using computer-generated sequences at the trial hub. Patients considered unfit were randomly assigned to EVAR (n = 197) or no intervention (n = 207) in EVAR-2. There was no blinding. INTERVENTIONS: EVAR, OR or no intervention. MAIN OUTCOME MEASURES: The primary end points were total and aneurysm-related mortality until mid-2015 for both trials. Secondary outcomes for EVAR-1 were reinterventions, costs and cost-effectiveness. RESULTS: In EVAR-1, over a mean of 12.7 years (standard deviation 1.5 years; maximum 15.8 years), we recorded 9.3 deaths per 100 person-years in the EVAR group and 8.9 deaths per 100 person-years in the OR group [adjusted hazard ratio (HR) 1.11, 95% confidence interval (CI) 0.97 to 1.27; p = 0.14]. At 0-6 months after randomisation, patients in the EVAR group had a lower mortality (adjusted HR 0.61, 95% CI 0.37 to 1.02 for total mortality; HR 0.47, 95% CI 0.23 to 0.93 for aneurysm-related mortality; p = 0.031), but beyond 8 years of follow-up patients in the OR group had a significantly lower mortality (adjusted HR 1.25, 95% CI 1.00 to 1.56, p = 0.048 for total mortality; HR 5.82, 95% CI 1.64 to 20.65, p = 0.0064 for aneurysm-related mortality). The increased aneurysm-related mortality in the EVAR group after 8 years was mainly attributable to secondary aneurysm sac rupture, with increased cancer mortality also observed in the EVAR group. Overall, aneurysm reintervention rates were higher in the EVAR group than in the OR group, 4.1 and 1.7 per 100 person-years, respectively (p < 0.001), with reinterventions occurring throughout follow-up. The mean difference in costs over 14 years was £3798 (95% CI £2338 to £5258). Economic modelling based on the outcomes of the EVAR-1 trial showed that the cost per quality-adjusted life-year gained over the patient's lifetime exceeds conventional thresholds used in the UK. In EVAR-2, patients died at the same rate in both groups, but there was suggestion of lower aneurysm mortality in those who actually underwent EVAR. Type II endoleak itself is not associated with a higher rate of mortality. LIMITATIONS: Devices used were implanted between 1999 and 2004. Newer devices might have better results. Later follow-up imaging declined, particularly for OR patients. Methodology to capture reinterventions changed mainly to record linkage through the Hospital Episode Statistics administrative data set from 2009. CONCLUSIONS: EVAR has an early survival benefit but an inferior late survival benefit compared with OR, which needs to be addressed by lifelong surveillance of EVAR and reintervention if necessary. EVAR does not prolong life in patients unfit for OR. Type II endoleak alone is relatively benign. FUTURE WORK: To find easier ways to monitor sac expansion to trigger timely reintervention. TRIAL REGISTRATION: Current Controlled Trials ISRCTN55703451. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and the results will be published in full in Health Technology Assessment; Vol. 22, No. 5. See the NIHR Journals Library website for further project information.

Strategy of endovascular versus open repair for patients with clinical diagnosis of ruptured abdominal aortic aneurysm: the IMPROVE RCT.

BACKGROUND: Ruptured abdominal aortic aneurysm (AAA) is a common vascular emergency. The mortality from emergency endovascular repair may be much lower than the 40-50% reported for open surgery. OBJECTIVE: To assess whether or not a strategy of endovascular repair compared with open repair reduces 30-day and mid-term mortality (including costs and cost-effectiveness) among patients with a suspected ruptured AAA. DESIGN: Randomised controlled trial, with computer-generated telephone randomisation of participants in a 1 : 1 ratio, using variable block size, stratified by centre and without blinding. SETTING: Vascular centres in the UK (n = 29) and Canada (n = 1) between 2009 and 2013. PARTICIPANTS: A total of 613 eligible participants (480 men) with a ruptured aneurysm, clinically diagnosed at the trial centre. INTERVENTIONS: A total of 316 participants were randomised to the endovascular strategy group (immediate computerised tomography followed by endovascular repair if anatomically suitable or, if not suitable, open repair) and 297 were randomised to the open repair group (computerised tomography optional). MAIN OUTCOME MEASURES: The primary outcome measure was 30-day mortality, with 30-day reinterventions, costs and disposal as early secondary outcome measures. Later outcome measures included 1- and 3-year mortality, reinterventions, quality of life (QoL) and cost-effectiveness. RESULTS: The 30-day mortality was 35.4% in the endovascular strategy group and 37.4% in the open repair group [odds ratio (OR) 0.92, 95% confidence interval (CI) 0.66 to 1.28; p = 0.62, and, after adjustment for age, sex and Hardman index, OR 0.94, 95% CI 0.67 to 1.33]. The endovascular strategy appeared to be more effective in women than in men (interaction test p = 0.02). More discharges in the endovascular strategy group (94%) than in the open repair group (77%) were directly to home (p < 0.001). Average 30-day costs were similar between groups, with the mean difference in costs being -£1186 (95% CI -£2997 to £625), favouring the endovascular strategy group. After 1 year, survival and reintervention rates were similar in the two groups, QoL (at both 3 and 12 months) was higher in the endovascular strategy group and the mean cost difference was -£2329 (95% CI -£5489 to £922). At 3 years, mortality was 48% and 56% in the endovascular strategy group and open repair group, respectively (OR 0.73, 95% CI 0.53 to 1.00; p = 0.053), with a stronger benefit for the endovascular strategy in the subgroup of 502 participants in whom repair was started for a proven rupture (OR 0.62, 95% CI 0.43 to 0.89; p = 0.009), whereas aneurysm-related reintervention rates were non-significantly higher in this group. At 3 years, considering all participants, there was a mean difference of 0.174 quality-adjusted life-years (QALYs) (95% CI 0.002 to 0.353 QALYs) and, among the endovascular strategy group, a cost difference of -£2605 (95% CI -£5966 to £702), leading to 88% of estimates in the cost-effectiveness plane being in the quadrant showing the endovascular strategy to be 'dominant'. LIMITATIONS: Because of the pragmatic design of this trial, 33 participants in the endovascular strategy group and 26 in the open repair group breached randomisation allocation. CONCLUSIONS: The endovascular strategy was not associated with a significant reduction in either 30-day mortality or cost but was associated with faster participant recovery. By 3 years, the endovascular strategy showed a survival and QALY gain and was highly likely to be cost-effective. Future research could include improving resuscitation for older persons with circulatory collapse, the impact of local anaesthesia and emergency consent procedures. TRIAL REGISTRATION: Current Controlled Trials ISRCTN48334791 and NCT00746122. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 22, No. 31. See the NIHR Journals Library website for further project information.

Defining the role of endovascular therapy in the treatment of abdominal aortic aneurysm: results of a prospective randomized trial.

Following publication of early registry data showing poor durability for first-generation endografts, EVAR was labeled by some as a failed experiment. The EVAR trial results prove such a pessimistic appraisal of EVAR wrong. In patients fit for open AAA repair EVAR w ith current devicesachieves a 3% benefit in operative and 4-year aneurysm-related mortality compared with open surgery. In patients unfit for open repair 30-day mortality is significantly greater and can no longer be described as safe. Nor does EVAR affect aneurysm-related or all-cause mortality in the 4-year follow-up. EVAR, at least for the first 4 years, is not safe or effective. Based on these results it seems appropriate in unfit patients to attend to concurrent medical problems before considering intervention for an asymptomatic aneurysm. Before the publication of this trial it was generally believed that EVAR would be of benefit in such patients; indeed, it was for the high-risk patient that EVAR was originally conceived. The focus changes from urgency to deploy EVAR to improvement of fitness, recognizing that such patients are very sick with multiple comorbidities. In both fit and unfit patients with large aneurysms most late deaths were cardiovascular related. The importance of risk factor management in both patient groups cannot be overstated. Despite the cost implications of EVAR and its failure to improve mid-term all-cause mortality over open AAA repair it is likely that the bias of both patients and surgeons toward this minimally invasive procedure means that it will continue to have a significant role. Experience and endograft developments have the potential to reduce postoperative complications; surveillance strategies could then be amended to reduce cost implications. Alternatively, over time the currently static rate of complications may increase as endografts reach the end of their working life. The long-term follow-up of patients in both the both EVAR Trials 1 and 2 has the potential for future surprises.