The study population consisted of patients treated for a ruptured infra-renal AAA in two aortic centers (Leeds, UK [Center 1] and Vienna, Austria [Center 2]). Patients in Center 1 were identified between 2007 and 2016, and in Center 2 between 2000 and 2016. All patients were treated prior to the publication of the first draft of the current NICE guidelines. Patients with ruptured iliac aneurysms, juxtarenal aortic aneurysms, thoraco-abdominal aortic aneurysms, mycotic aneurysms and ruptured abdominal-iliac aneurysm were excluded from the study.

The stability of the patients was defined according to the main clinical definition of blood pressure of at least 80 mmHg mean systolic (8). Treatment decisions were determined based on: anatomical criteria for rEVAR according the device instruction for use and hemodynamic stability of the patient on arrival at the hospital. EVAR teams were available 24/7, 365 days a year in both centers across the duration of the study. EVAR teams were called in once it was known that there was a patient on route, or the decision has been taken to re-offer rEVAR. rEVAR was performed via femoral access in all cases. The decision to perform rEVAR with a bifurcated graft or aorto-uni-iliac configuration in conjunction with a femoro- femoral bypass was left to the discretion of the operating team. rOSR was performed in most of the cases using either a mid-line or vertical approach depending on operator preference, after achieving proximal aortic control at either the supracoeliac, supra-renal or infra-renal aortic level, the rOSR was performed by using either a tube graft or a bifurcated graft. Grafts made of knitted polyester (Dacron) or polytetrafluoroethylene (PTFE) grafts were used at the discretion of the operating surgeon. Permissive hypotension and low volume fluid administration was permitted as standard (9).

Patients were identified from registries of rAAA performed at each center. The following demographic variables and comorbidities, recorded at time of surgery were included in the analysis: age, gender, body mass index (BMI), history of smoking (yes/no), hypertension (HTN), diabetes mellitus, hypercholesterolemia, coronary artery disease (CAD), cerebrovascular disease, pulmonary disease and any known malignancy. Renal function was assessed using glomerular filtration rate (GFR) and creatinine. Patient hemodynamic stability at presentation was determined from electronic case records. The date and cause of death was identified from case records. Overall survival was calculated as the number of days from surgery to death from any cause or last follow-up date. whatever occurred earlier. Survival time was treated as censored if a patient was alive at last follow-up.

The study was approved by the local ethics review committee (EC 2086/2012) at Center 2, conducted according to the Declaration of Helsinki and registered the study ID research registry 5,637. According to the local authorities at Center 1, ethics committee approval was not deemed necessary for this retrospective study. The study adhered to the STROCSS criteria (10). Given that all procedures were performed under emergency conditions it was not possible to obtain a complete history in all patients and missing values are reported in Table 1.

Female patients, male patients older than 70 years with rEVAR, and male patients up to 70 years of age with rOSR were considered as NICE-compliers. Female patients, and male patients older than 70 years with rOSR, and male patients up to 70 years of age with rEVAR were considered as NICE-non-compliers. To additionally account for the patients' hemodynamic stability, we defined the following modified NICE (mNICE) criteria: Hemodynamically unstable patients treated with rOSR, and stable patients treated according to the NICE criteria were considered as mNICE-compliers. On the other hand, hemodynamically unstable patients treated with rEVAR, and stable patients treated contradictory to the NICE criteria were considered as mNICE-non-compliers.

Categorical variables are described by absolute numbers and relative frequencies, and continuous variables by mean and standard deviation (SD) or median and interquartile range (IQR) in case of non-normal distribution. The inverse Kaplan–Meier method (11) was used to estimate the median follow-up time. To evaluate the impact of the proposed NICE Guidelines in rAAA patients on overall survival, we emulated a hypothetical target trial comparing the outcome under usual care to that expected under compliance to NICE (12). The hypothetical target trial methodology simulates a randomized trial in which patients are randomized to either usual care or treatment according to NICE criteria. The outcomes under both alternatives are then statistically compared. The outcome under usual care can be estimated from our total study cohort, and the sub-cohort of NICE-compliers serves as the basis to estimate the outcome if all patients were treated compliant to NICE. However, these patients are a sub-cohort of the total study cohort and thus might differ in their baseline characteristics from the total cohort. Therefore, we first evaluated differences in baseline characteristics between the total cohort and the NICE-compliers by propensity score (multivariable logistic regression) analyses using compliance to NICE (yes/no) as binary outcome variable and age, sex, diabetes mellitus, chronic lung disease, chronic kidney disease, and stability as covariates. The inverted predicted probabilities of compliance (inverse probability of treatment weights, IPW) were then used to weight the outcomes in the sub-cohort of NICE-compliers (13). Considering patients of center 1 (n = 146), the variable stability was not included in the propensity score model, since it was missing in 32% of the cases. On the other hand, 14 observations were excluded from the propensity score model of center 2, due to missing values in the baseline variables diabetes, chronic lung disease, chronic kidney disease, and/or stability, resulting in a total sample size of n = 138 patients in center 2. Altogether, n = 284 patients were used for statistical comparisons of overall survival. In a second step, using the unweighted observations of the total cohort or the IPW-weighted observations of the NICE-compliers, the Kaplan–Meier method was applied to estimate survival probabilities, and risk ratios were calculated to compare the two cohorts at the pre-specified time points 30 days, 1 year, and 5 years after procedure. This Kaplan–Meier analysis was also performed for the subgroups of men aged ≤70 years, of men aged >70 years, and of women, respectively. Bootstrap percentile confidence intervals were calculated for the risk ratios, using the balanced bootstrap method with 10,000 samples stratified by the center. This method was used to account for the special dependency-structure of the two cohorts (the “NICE-complier” cohort is an IPW-weighted sub-cohort of the “usual care” cohort). To evaluate the impact of the modified NICE criteria compared to NICE and usual care, only patients of center 2 were considered (n = 138). Patients of center 1 were excluded from this sub-analysis due to the large number of missing values in the baseline variable stability. Again, propensity score models were used and the three IPW-weighted cohorts (“mNICE compliers”, “NICE compliers”, and “usual care”) were compared with respect to overall survival as described before. All statistical analyses were performed using the software system SAS (version 9.4. (2016), SAS Institute Inc. Cary, NC, USA).

This study included 298 patients with a rAAA, 112 EVARs were performed (58 patients from Center 1 and 54 patients from Center 2) and 186 OSRs were performed (88 patients from Center 1 and 98 patients from Centre 2), Figure 1.

The mean (SD) age of patients included in the study was 74.3 (9.5) years and 249 patients (83.6%) were men. Baseline characteristics are summarized in Table 1 and Supplementary Table S1. The median (IQR) follow-up time was 5.9 (4.6–7.2) and 7.4 (1.8–10.1) years in Center 1 and 2, respectively. Morphological characteristics of rAAA could be assessed for 102 patients from Center 1 and for 104 patients from Center 2. The data was extrapolated from preoperative computer tomography (CT) scans and is depicted in Table 2.

Examining how treatment of the patients relates to the NICE recommendations, there were 144 NICE compliers (19 women undergoing rEVAR; 66 men >70 years undergoing rEVAR; and 59 men ≤70 years undergoing rOSR), representing 48.3% of the study population. There were 154 patients not compliant with NICE recommendations (30 women undergoing rOSR; 27 men ≤70 years undergoing rEVAR; and 97 men >70 years undergoing rOSR, representing 51.7% of the study population, Figure 1.

Overall, 184 deaths (68 [37%] with rEVAR and 116 [63%] with rOSR) were observed during the study period. The IPW-weighted Kaplan–Meier estimate of cumulative survival under compliance to NICE is compared to the unweighted estimate under usual care for the total cohort is shown in Figure 2A. Overall survival under usual care is estimated as 69.2% at 30 days, 56.5% at one year, and 42.4% at 5 years. Under compliance to NICE the corresponding numbers were 73.1%, 60.2% and 42.9%, respectively Figure 2A. The risk ratios at these time points, comparing NICE-compliance to usual care, were 0.88 [95% Confidence-Interval: 0.67–1.09], 0.92 [0.76–1.08], and 0.99 [0.87–1.12], respectively Table 3.

Of the 112 patients in this study who had a rEVAR, 66 patients (59%) were men aged >70 years and 27 patients (24.1%) were men aged ≤70 years. Of the 186 patients who had a rOSR, 59 patients (31.7%) were men aged ≤70 years and 97 patients (52.2%) were men aged >70 years. Men aged ≤70 years showed slightly better survival under usual care than under compliance to NICE, 79% survival at 30 days, 66.8% at one year and 60.2% at 5 years vs. 73.7% at 30 days, 63.8% at one year and 58.8% at 5 years, respectively Figure 2C. Men aged >70 years had better estimated survival under compliance to NICE in the early phase (up to 2 years) of follow-up: usual care 63.7% survival at 30 days, 51% at one year, 35.3% at 5 years vs. NICE-compliance 71.3% at 30 days, 57.6% at one year and 33.7% at 5 years Figure 2D. The respective risk ratios are given in Table 3.

Overall 19 patients (17%) who had undergone rEVAR and 30 patients (16.1%) who had a rOSR were women. Women slightly benefitted from compliance to NICE in the early post-procedural phase: Under usual care survival probability was estimated as 70.7% at 30 days, 57.4% at one year and 37% at 5 years, compared to 76.2% at 30 days, 59.6% one year, 34.4% at 5 years under compliance to NICE Figure 2B.

Data relating to patient hemodynamic stability was unavailable for 46 patients of center 1, and 1 patient of center 2 (15.8%). At presentation, 74.5% of patients undergoing rEVAR and 54.8% undergoing rOSR were deemed hemodynamically stable. The stability of the patients was defined according to the main clinical definition of blood pressure of at least 80 mmHg mean systolic on arrival (8). In a subgroup analysis of 138 patients (from center 2), we compared the estimated overall survival under usual care to that under compliance to mNICE (including hemodynamic stability) and NICE. Compliance to mNICE did marginally improve survival in contrast to compliance to NICE and usual care: Survival under mNICE was estimated as 69.4% at 30 days, 54.1% at one year and 40.4% at 5 years, compared to 68.1% survival at 30 days, 53.9% at 1 year and 40.6% at 5 years under NICE compliance, and 67.8% survival at 30 days, 51.3% at 1 year and 39.8% at 5 years under usual care Figure 3A and Table 4. Female patients seem to show a slight advantage under mNICE strategy in the early post-procedural phase, 70.2% survival at 30 days, 53.9% at 1 year, 35.6% at 5 years vs. NICE-strategy 61.6% survival at 30 days, 48.5% at one year, 31.6% at 5 years and usual care 67.6% survival at 30 days, 52.0% at 1 year, 39.0% at 5 years, respectively Figures 3B–D. The estimated risk ratios are given in Table 4.