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Editor's Choice – Covered vs. Bare Metal Stents in the Reconstruction of the Aortic Bifurcation: Early and Midterm Outcomes from the COBRA European Multicentre Registry

Published:March 22, 2022DOI:https://doi.org/10.1016/j.ejvs.2021.12.020

      Objective

      To report outcomes following endovascular revascularisation for severe aorto-iliac occlusive disease (AIOD) using covered (CS) or bare metal (BMS) stent(s).

      Methods

      This was a retrospective cohort study including patients who underwent treatment with CS or BMS for AIOD between November 2012 and March 2020 in 12 European centres. Outcome measures included death, freedom from target lesion revascularisation (TLR), major amputation, and major adverse cardiac and cerebrovascular events (MACCE).

      Results

      Overall, 252 patients (53% males; mean age 65 ± 10 years) were included (102 with a bare metal and 150 with a covered aortic stent); 122 (48%) presented with chronic limb threatening ischaemia (CLTI). Severe arterial calcification was noted in > 65% of patients, 70% presented with Trans-Atlantic Societies Consensus (TASC) D lesions, 32% and 46% had aortic or iliac chronic total occlusion (CTO), respectively. Median follow up was 17 months (range 6 – 40; none lost to follow up). Median inpatient stay was two days (range two to four). During the first 30 days, two patients died (both with covered aortic stents, because of cardiovascular events), none required TLR, two (1%) patients had a major amputation (all presented with CLTI), and three (1%) had a MACCE. At 17 months, mortality (BMS 14% vs. CS 7%, hazard ratio [HR] 0.97, 95% confidence interval [CI] 0.42 – 2.26, p = .94, log rank test) and TLR (11% vs. 10%, HR 1.98, 95% CI 0.89 – 4.43, p = .095) did not differ statistically significantly between the two groups; only three patients had a major limb amputation during late follow up (all with a covered stent). In a multivariable model, the use of an aortic CS did not influence TLR. In a conditional Cox regression, however, the concomitant use of aortic and iliac CSs was associated with improved freedom from TLR.

      Conclusion

      Endovascular reconstruction with aortic CSs or BMSs for severe AIOD showed comparable midterm performance. The use of both aortic and iliac CSs seems to be associated with reduced TLR.

      Keywords

      This is the first international multicentre study reporting medium term outcomes in patients undergoing complex endovascular reconstruction for severe aorto-iliac occlusive disease with covered vs. bare metal aortic stents. The study showed comparable outcomes between patients treated by covered and bare metal stents; the use of both aortic and iliac covered stents might be associated with reduced need for re-interventions in a multivariable model.

      Introduction

      Peripheral arterial occlusive disease (PAOD) affects more than 200 million people worldwide and remains the leading cause of major limb amputations.
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      • Dua A.
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      Epidemiology of peripheral arterial disease and critical limb ischemia.
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      • Hinchliffe R.J.
      Peripheral artery disease.
      Patients with PAOD and intermittent claudication (IC) or chronic limb threatening ischaemia (CLTI) often have aorto-iliac occlusive disease (AIOD).
      • Conte M.S.
      • Bradbury A.W.
      • Kolh P.
      • White J.V.
      • Dick F.
      • Fitridge R.
      • et al.
      Global Vascular Guidelines on the management of chronic limb-threatening ischemia.
      ,
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      Peripheral arterial disease: epidemiology, natural history, diagnosis and treatment.
      ,
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      Epidemiology, classification, and modifiable risk factors of peripheral arterial disease.
      As a result, aorto-iliac interventions, either surgical or endovascular, are common.
      • Grimme F.A.
      • Goverde P.C.
      • Verbruggen P.J.
      • Zeebregts C.J.
      • Reijnen M.M.
      Editor's Choice - First results of the covered endovascular reconstruction of the aortic bifurcation (CERAB) technique for aortoiliac occlusive disease.
      • Goverde P.C.
      • Grimme F.A.
      • Verbruggen P.J.
      • Reijnen M.M.
      Covered endovascular reconstruction of aortic bifurcation (CERAB) technique: a new approach in treating extensive aortoiliac occlusive disease.
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      • Weiss B.
      • Topel I.
      • Steinbauer M.
      Results of hybrid procedures for treatment of aortoiliac Trans-Atlantic Inter-Society Consensus II D lesions with self-expanding covered heparin-bonded stent grafts.
      The Trans-Atlantic Inter-Society Consensus II (TASC II) classified AIOD by location and severity of disease and produced recommendations regarding surgical or endovascular management.
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      • et al.
      Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II).
      In recent years, however, there have been notable advances in endovascular techniques for TASC II C and D AIOD lesions.
      • Grimme F.A.
      • Goverde P.C.
      • Verbruggen P.J.
      • Zeebregts C.J.
      • Reijnen M.M.
      Editor's Choice - First results of the covered endovascular reconstruction of the aortic bifurcation (CERAB) technique for aortoiliac occlusive disease.
      ,
      • Goverde P.C.
      • Grimme F.A.
      • Verbruggen P.J.
      • Reijnen M.M.
      Covered endovascular reconstruction of aortic bifurcation (CERAB) technique: a new approach in treating extensive aortoiliac occlusive disease.
      ,
      • Kavaliauskiene Z.
      • Antusevas A.
      • Kaupas R.S.
      • Aleksynas N.
      Recent advances in endovascular treatment of aortoiliac occlusive disease.
      ,
      • Taeymans K.
      • Goverde P.
      • Lauwers K.
      • Verbruggen P.
      The CERAB technique: tips, tricks and results.
      Among these is the Covered Endovascular Reconstruction of Aortic Bifurcation (CERAB) technique,
      • Grimme F.A.
      • Goverde P.C.
      • Verbruggen P.J.
      • Zeebregts C.J.
      • Reijnen M.M.
      Editor's Choice - First results of the covered endovascular reconstruction of the aortic bifurcation (CERAB) technique for aortoiliac occlusive disease.
      • Goverde P.C.
      • Grimme F.A.
      • Verbruggen P.J.
      • Reijnen M.M.
      Covered endovascular reconstruction of aortic bifurcation (CERAB) technique: a new approach in treating extensive aortoiliac occlusive disease.
      • Uhl C.
      • Betz T.
      • Weiss B.
      • Topel I.
      • Steinbauer M.
      Results of hybrid procedures for treatment of aortoiliac Trans-Atlantic Inter-Society Consensus II D lesions with self-expanding covered heparin-bonded stent grafts.
      ,
      • Taeymans K.
      • Goverde P.
      • Lauwers K.
      • Verbruggen P.
      The CERAB technique: tips, tricks and results.
      that is designed to achieve an anatomical reconstruction of the aorto-iliac segment using covered aortic and iliac stents. Despite promising outcomes in single centre cohorts from high volume institutions,
      • Grimme F.A.
      • Goverde P.C.
      • Verbruggen P.J.
      • Zeebregts C.J.
      • Reijnen M.M.
      Editor's Choice - First results of the covered endovascular reconstruction of the aortic bifurcation (CERAB) technique for aortoiliac occlusive disease.
      ,
      • Goverde P.C.
      • Grimme F.A.
      • Verbruggen P.J.
      • Reijnen M.M.
      Covered endovascular reconstruction of aortic bifurcation (CERAB) technique: a new approach in treating extensive aortoiliac occlusive disease.
      ,
      • Taeymans K.
      • Goverde P.
      • Lauwers K.
      • Verbruggen P.
      The CERAB technique: tips, tricks and results.
      there is a lack of multicentre series reporting medium term outcomes in patients treated for severe AIOD using covered stents. Furthermore, many endovascular specialists opt to treat AIOD using bare metal stents and non-covered stent grafts. A direct comparison between the two modalities has not been attempted.
      The aim of this study is to report real world clinical outcomes in patients with severe AIOD who have undergone endovascular reconstruction in vascular centres across Europe and compare outcomes between patients treated with a covered aortic stent with those treated with a bare metal aortic stent.

      Methods

      Patient selection

      This is a retrospective analysis of institutional datasets, which were prospectively maintained (see Supplementary Table S1). The study, protocol, and analysis plan were registered in February 2020 (ISRCTN registry reference: 19619299). European vascular centres that routinely perform aorto-iliac endovascular procedures were invited to participate by KS, AS, AA, and HZ in February 2020. All patients undergoing aorto-iliac reconstruction with at least one aortic stent (1 November 2012 to 30 March 2020) in each participating centre were screened locally in April 2020, using departmental databases, multidisciplinary team meeting notes, and electronic records. Centres that could provide full data for at least five aorto-iliac endovascular reconstructions were eligible to take part. Included in this study were consecutive patients with AIOD with ≥ 50% stenosis of the infrarenal aorta and/or common iliac artery(-ies) based on a computed tomographic angiogram (CTA) causing IC or CLTI. Patients were categorised into two groups based on the nature of the aortic stent used (covered or bare metal), regardless of the design of the iliac stents. Exclusion criteria were acute AIOD; aortic coarctation; isolated kissing stent reconstruction without aortic stents; aortic injury/trauma; suprarenal/visceral reconstruction; infrarenal abdominal aortic aneurysm; penetrating aortic ulcer(s); aortic dissection. All individual participating NHS centres obtained approval as “service evaluation and audit”. The present authors applied for NHS Review Ethics Committee (REC) review but given the nature of the study and no reporting of identifiable data, were advised that a REC opinion was not necessary. Outside the UK, individual local and regional approvals were sought and were in place. All patients provided written informed consent for the procedure(s) and their data to be used for research.

      Device and procedural details

      The treatment of the aortic lesions, iliac arteries, and outflow (common femoral arteries and infra-inguinal vessels) were operator dependent. All lead operators were qualified vascular/endovascular surgeons and/or interventional radiologists. Procedures were performed either in an angiographic suite or a hybrid theatre. All patients had undergone cross sectional imaging pre-operatively; a CTA with at least 1 mm slices had been obtained to plan the endovascular interventions. The mode of anaesthesia was dependent on local practice(s), need for concomitant procedures, and patients’ comorbidities. Devices were deployed as per manufacturers’ instructions. The aortic stents were deployed first, followed by iliac stents protruding into the aortic stent by at least 10 mm. The aortic stents were deployed as close to the aortic bifurcation as possible; however, each procedure was performed based on the operator’s preference and intra-operative imaging. Supplementary Table S2 lists the devices that were used.

      Clinical follow up

      All patients received best medical therapy consisting of an antiplatelet (or anticoagulant if indicated) with clopidogrel 75 mg or aspirin 75 mg pre-operatively and statin therapy, advice regarding smoking cessation, and referral for exercise therapy for claudicants if available at the participating centre. Patients were reviewed clinically post-operatively at set intervals as per local departmental practice. Patients underwent clinically driven imaging based on clinical findings at their post-operative follow up appointments. Patients were offered target lesion revascularisation (TLR) when presenting with new symptoms (e.g., new onset claudication, rest pain, or tissue loss) and/or if they were found to have a stenosis ≥ 50% within the previously treated lesion(s) or dominant outflow vessel on imaging. Follow up data were recorded in digital databases; missing data were retrieved retrospectively in April 2020. Post-operative medical therapy and follow up procedures were uniform between centres. Causes of death were obtained based on death certificates and electronic files.

      Reporting, definitions, and outcomes

      The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidance was used during protocol design to ensure accurate reporting of study findings (Supplementary Fig. S1). The latest available pre-operative CTA and intra-operative angiogram were used to define the degree and length of disease as well as calcification of the aorta and iliac arteries. Calcification of the target lesions was reported using a modification of the score reported by Fanelli et al.
      • Fanelli F.
      • Cannavale A.
      • Gazzetti M.
      • Lucatelli P.
      • Wlderk A.
      • Cirelli C.
      • d’ Adamo A.
      • Salvatori F.M.
      Calcium burden assessment and impact on drug-eluting balloons in peripheral arterial disease.
      assigning a score of 1 – 4 (Grade 1 – 4) based on the number of arterial quadrants exhibiting substantial calcification. A Grade of 3 or 4 was considered to be “severe”. The institutional lead investigator reported the relevant degree of calcification at each centre.
      • Rocha-Singh K.J.
      • Zeller T.
      • Jaff M.R.
      Peripheral arterial calcification: prevalence, mechanism, detection, and clinical implications.
      Diagnoses and clinical events were defined as per the American Heart Association (AHA) guidance for cardiovascular studies
      • Hicks K.A.
      • Tcheng J.E.
      • Bozkurt B.
      • Chaitman B.R.
      • Cutlip D.E.
      • Farb A.
      • et al.
      2014 ACC/AHA Key data elements and definitions for cardiovascular endpoint events in clinical trials: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Data Standards (Writing Committee to Develop Cardiovascular Endpoints Data Standards).
      and the reporting standards of the Society for Vascular Surgery (SVS).
      • Stoner M.C.
      • Calligaro K.D.
      • Chaer R.A.
      • Dietzek A.M.
      • Farber A.
      • Guzman R.J.
      • et al.
      Reporting standards of the Society for Vascular Surgery for endovascular treatment of chronic lower extremity peripheral artery disease.
      For major adverse cardiac and cerebrovascular events (MACCE), the following definition was used: death secondary to myocardial infarction, stroke, or coronary vessel revascularisation, or occurrence of non-fatal myocardial infarction, stroke, or coronary revascularisation.
      • Behrendt C.A.
      • Bertges D.
      • Eldrup N.
      • Beck A.W.
      • Mani K.
      • Venermo M.
      • et al.
      International Consortium of Vascular Registries Consensus Recommendations for Peripheral Revascularisation Registry Data Collection.
      A diagnosis of diabetes was recorded based on past medical case records and pre-existing medications. A diagnosis of hypertension was made based on baseline blood pressure and medication.
      • Hicks K.A.
      • Tcheng J.E.
      • Bozkurt B.
      • Chaitman B.R.
      • Cutlip D.E.
      • Farb A.
      • et al.
      2014 ACC/AHA Key data elements and definitions for cardiovascular endpoint events in clinical trials: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Data Standards (Writing Committee to Develop Cardiovascular Endpoints Data Standards).
      Chronic kidney disease (CKD) was diagnosed based on latest available estimated glomerular filtration (eGFR) level. AKI was defined as per the Kidney Disease Improving Global Outcomes (KDIGO) criteria.
      The main outcome measures were mortality, target lesion revascularisation (TLR), major lower limb amputation, and MACCE. Freedom from surgical conversion was also reported.

      Statistical analysis

      All analyses were performed using SPSS version 26.0 (IBM, Armonk, NY, USA) and R for Windows (version 3.6.1), with the support of an independent qualified medical statistician, based on a statistical analysis plan which was drawn before the complete datasets were available to investigators. TB and AS were responsible for all statistical analyses, blinded to data source. Data were inspected prior to analyses and pre-processed to ensure uniformity of format by TB, AS, AA, and KS. All data relating to post-operative events, devices used, and intra-operative characteristics were complete (no missing data). Normality of continuous variables was assessed using the Shapiro-Wilk test, as well as by examining skewness and kurtosis. Means and standard deviations are reported for each group. For categorical variables, the number (and percentage) of patients in each category is reported. Mean values with standard deviation are reported for normally distributed continuous variables; median values with range are reported for non-normally distributed continuous variables. Fisher’s test was used to assess differences between categorical variables. Kaplan–Meier curves were constructed regarding the main outcomes of interest during long term follow up for patients having covered and bare metal aortic stents. The log rank test was used to compare outcomes of interest (univariable comparison) at latest available follow up based on the Kaplan–Meier curves. A Cox regression was performed to assess parameters that may be associated with endovascular re-intervention during long term follow up (the most common post-operative event during follow up). Two types of Cox regression modelling were performed: (i) a model where pre-specified anatomical parameters which might impact TLR were included alongside the type of procedure (following discussion between the investigators, the following were included in this model: aortic chronic total occlusion, iliac chronic total occlusion, aortic lesion length, total iliac lesion length, TASC classification, presence of severe calcification); (ii) a stepwise model where demographics, comorbidities, and anatomical characteristics were all entered alongside the type of procedure, that is use of bare metal vs. covered stents. Given the size of the cohort and rarity of clinical events such as major amputation, further multivariable analyses were not possible. A p value < .050 was considered to be statistically significant.

      Results

      A total of 252 patients (134 males, 53%; mean age: 65 ± 10 years; 102 with a bare metal and 150 with a covered aortic stent) treated between November 2012 and March 2020 were included from a total of 12 centres (Supplementary Table S1). Chronic kidney disease, inclusive of stages II–V (80 patients, 32%), hypertension (170 patients, 68%), diabetes mellitus (76 patients, 30%), and ischaemic heart disease (71 patients, 28%) were the commonest comorbidities – as expected in a population with symptomatic severe AIOD. All baseline demographics and patient characteristics are presented in Table 1. Indications for treatment comprised mild/moderate claudication (Rutherford 1, three patients, Rutherford 2, 19 patients, 9%), severe claudication (Rutherford 3, 108 patients, 43%), rest pain (Rutherford 4, 61 patients, 24%), and tissue loss (Rutherford 5/6, 60 patients, 24%); none required treatment as an emergency (defined as treatment within 24 hours of presentation) – overall, 48% of patients had CLTI. Of those presenting with Rutherford 1/2 symptomatology, all had lifestyle limiting claudication; one patient had had a previous iliac angioplasty and presented again with an occlusion and claudication and one patient had iliac occlusions in the context of claudication and a 6.5 cm thoracic aortic aneurysm. Anatomical features of the AIOD and lesion characteristics are listed in Table 1. Procedural details are listed in Table 2.
      Table 1Baseline demographics, clinical, and anatomical characteristics of all 252 patients, and 102 patients in the bare metal stent and 150 patients in the covered stent group, for reconstruction of the aortic bifurcation for aorto-iliac occlusive disease
      CharacteristicAll patients (n = 252)Bare metal stents (n = 102)Covered stents (n = 150)p value
      Mean age – y65 ± 1064 ± 1165 ± 10.26
      Male sex134 (53)49 (48)85 (57).17
      Arterial hypertension170 (68)80 (78)90 (60).002
      Diabetes mellitus76 (30)26 (26)50 (33).18
      Tobacco use107 (43)52 (51)55 (37).024
      End stage renal disease requiring dialysis4 (2)2 (2)2 (1)1.0
      Coronary heart disease71 (28)33 (32)38 (25).22
      Statin use130 (52)47 (46)83 (55).15
      Aortic chronic total occlusion80 (32)28 (28)52 (35).22
      Iliac chronic total occlusion, any117 (46)27 (27)90 (60).001
      TASC II A2 (1)0 (0)2 (1).51
      TASC II B54 (21)27 (27)27 (18).10
      TASC II C20 (8)15 (15)5 (3).001
      TASC II D176 (70)60 (59)116 (77).002
      Aortic lesion length – mm40 (25, 62)48 (40, 57)33 (30, 40).004
      Right iliac lesion length – mm30 (0, 57)20 (0, 31)40 (0, 270).001
      Left iliac lesion length – mm30 (0, 58)23 (10, 37)30 (23, 44).004
      Aortic calcification
      Calcification of the target lesions was reported using a modification of the score reported by Fanelli et al.21 assigning a score of 1–4 based on the number of quadrants exhibiting substantial calcification.
       Grade 144 (18)21 (21)23 (15).29
       Grade 248 (19)25 (25)24 (16).095
       Grade 351 (20)29 (28)22 (15).008
       Grade 481 (32)14 (14)67 (45).001
      Calcification right iliac lesion
      Calcification of the target lesions was reported using a modification of the score reported by Fanelli et al.21 assigning a score of 1–4 based on the number of quadrants exhibiting substantial calcification.
       Grade 137 (15)15 (15)22 (15).99
       Grade 249 (20)18 (18)31 (21).53
       Grade 336 (14)15 (15)21 (14).89
       Grade 445 (18)4 (4)41 (28).001
      Calcification left iliac lesion
      Calcification of the target lesions was reported using a modification of the score reported by Fanelli et al.21 assigning a score of 1–4 based on the number of quadrants exhibiting substantial calcification.
       Grade 144 (18)15 (15)29 (20).33
       Grade 241 (16)19 (19)22 (15).41
       Grade 328 (11)11 (11)17 (11).87
       Grade 454 (22)8 (8)46 (31).001
      Data presented as n (%), or mean ± standard deviation, or median (interquartile range). TASC = Trans-Atlantic Society Consensus.
      Calcification of the target lesions was reported using a modification of the score reported by Fanelli et al.
      • Fanelli F.
      • Cannavale A.
      • Gazzetti M.
      • Lucatelli P.
      • Wlderk A.
      • Cirelli C.
      • d’ Adamo A.
      • Salvatori F.M.
      Calcium burden assessment and impact on drug-eluting balloons in peripheral arterial disease.
      assigning a score of 1–4 based on the number of quadrants exhibiting substantial calcification.
      Table 2Procedural details reported for all 252 patients, and 102 patients in the bare metal stent and 150 patients in the covered stent group, for reconstruction of the aortic bifurcation for aorto-iliac occlusive disease
      CharacteristicAll patients (n = 252)Bare metal stents (n = 102)Covered stents (n = 150)p value
      Subintimal recanalisation of aorta1 (0.5)1 (1)0.34
      Subintimal recanalisation iliac(s)67 (27)14 (14)53 (36).001
      Single femoral access46 (30)36 (36)10 (19).031
      Single brachial access13 (8)10 (10)3 (6).37
      Bilateral femoral access87 (56)45 (44)42 (79).001
      Combined access32 (13)13 (13)19 (13).96
      Number of aortic stents
       One stent228 (91)97 (94)129 (88).004
       Two stents28 (11)5 (5)23 (15).009
       Three stents2 (1)1 (1)1 (0.7).78
      Diameter of aortic stent – mm14 (12, 16)14 (14, 14)12 (12, 16).012
      Length of aortic stent(s) – mm41 (38, 60)50 (40, 60)41 (29.5, 59).005
      Number of iliac stents, right side
       None72 (29)57 (56)15 (10).001
       One stent121 (48)37 (36)84 (57).002
       Two stents52 (21)8 (8)44 (30).001
       Three stents5 (2)0 (0)5 (3).061
      Diameter of iliac stent – mm7 (0, 8)8 (7, 8)8 (7, 9).42
      Number of iliac stents, left side
       None67 (27)55 (54)12 (8).001
       One stent132 (53)40 (39)92 (62).001
       Two stents47 (19)6 (6)41 (28).001
       Three stents5 (2)1 (1)4 (3).34
      Diameter of iliac stent – mm8 (0, 8)8 (7, 8)8 (7, 9).42
      Length of iliac stent(s) – mm56 (0, 59)57 (39, 60)57 (57, 59).69
      CFA endarterectomy47 (19)12 (12)35 (24).020
      External iliac stent74 (30)22 (22)52 (35).023
      Internal iliac stent3 (1.9)2 (2)1 (1.9).97
      Data presented as n (%) or median (interquartile range). CFA = common femoral artery.
      Overall, 70% (176 patients) had TASC II D AIOD and 8% (20 patients) had TASC II C AIOD, with 32% and 46% demonstrating aortic or iliac chronic total occlusion (CTO), respectively. Severe aortic and/or iliac artery calcified lesions were noted in 65% of patients on at least one side (Table 2). Of note, patients who had a bare metal aortic stent vs. patients who had a covered aortic stent were lesslikely to have an iliac CTO (27% vs. 60%, p = .001), have TASC D disease (59% vs. 77%, p = .002), and had shorter iliac lesions (Table 2). At the same time, those patients who had a bare metal aortic stent were not less likely to have an aortic CTO (28% vs. 35%, p = .22). There was great variability in terms of the length and degree of calcification of the lesions between the two groups, as summarised in Table 2. Patients who had a covered aortic stent were also more likely to have had a subintimal recanalisation of at least one iliac artery (14% vs. 36%, p = .001; Table 2). A total of 78 patients (31%) were treated in the form of a formal Covered Endovascular Repair of the Aortic Bifurcation (CERAB) technique, that is with at least one covered aortic stent and two covered common iliac stents into the aortic stent. The numbers of stents used, stent diameters, and concomitant procedures performed are listed in Table 2. Again, there was considerable variability between the groups.

      Post-operative outcomes (30 days and medium term follow up)

      30 day (early) outcomes

      Table 3 summarises outcomes at 30 days. All procedures were completed successfully. No patients were lost to early follow up (30 days). The median inpatient stay after the procedure was two days (range two to four days); a total of 10 patients (4%) were admitted to a critical care facility post-operatively for close monitoring (none of these admissions were elective) – the decision to admit these patients to intensive care was made by the operating anaesthetist for each patient. The median stay in critical care was two days (range one to two days); the median hospital stay of those patients was four days (range three to four days). Patients with a covered aortic stent spent on average one extra day in hospital (median of two days [range: two to three days] vs. median of three days [range: two to seven days], p = .002). During the first 30 post-operative days, two patients died because of MACCEs (both with covered aortic stents), none required TLR, two (1%) patients had a major lower limb amputation, and three (1%) had non-fatal MACCE. Twenty two (9%) patients developed access site complications which required further treatment (14 had antibiotics for a groin wound infection, two had evacuation of a haematoma, one had a surgical pseudoaneurysm repair, and eight had thrombin injection for a pseudoaneurysm). Eight patients (n = 8, 3%) developed acute kidney injury; however, no patients required renal dialysis or developed a drop in eGFR of more than 25% during the first 30 days. There were no differences between patients with a bare metal stent and a covered aortic stent at 30 days with regards to death (0 vs. 1%, p = .51), major lower limb amputation (0 vs. 1%, p = .51), MACCE (1% for both groups), acute kidney injury (2% vs. 4%, p = .36), or access site complications (8% vs. 9%, p = .68) (summarised in Table 3).
      Table 3Post-operative adverse events at 30 days for all 252 patients, and 102 patients in the bare metal stent and 150 patients in the covered stent group, for reconstruction of the aortic bifurcation for aorto-iliac occlusive disease
      EventsAll patients (n = 252)Bare metal stents (n = 102)Covered stents (n = 150)p value
      Death2 (1)0 (0)2 (1)
      Target lesion revascularisation0 (0)0 (0)0 (0).24
      Major lower limb amputation2 (1)0 (0)2 (1)
      Major adverse cardiac event3 (1)1 (1)2 (1).24
      Access site complications22 (9)8 (8)14 (9).79
      Acute kidney injury8 (3)2 (2)6 (4).68
      Aortic rupture, intra-operative2 (1)0 (0)2 (1).47
      Stroke1 (0.4)1 (1)0 (0).24
      Data are presented as n (%). AKI = Acute Kidney Injury – defined as per the Kidney Disease Improving Global Outcomes (KDIGO) Consortium, using serum creatinine measurements.

      Medium term outcomes (30th post-operative day until end of follow up)

      The median follow up was 17 months (range 6 – 40 months) and no patient was lost to follow up. A total of 24 patients (10%; 14 [14%] with a bare metal aortic stent vs. 10 [7%] with a covered aortic stent, p = .072) died during long term follow up; Kaplan–Meier curve analysis disclosed no differences between patients with a bare metal aortic stent vs. those with a covered aortic stent (HR 0.97, 95% CI 0.42 – 2.26, p = .94, log rank test) (Supplementary Fig. S2).
      A total of 26 patients (10%; 11 [11%] with a bare metal aortic stent vs. 15 [10%] with a covered aortic stent, p = .90) required target lesion revascularisation (TLR) during follow up (18 [69%] endovascular and eight [31%] open, that is conversion to surgery). Figure 1 represents a Kaplan–Meier curve comparing freedom from TLR between those with a bare metal vs. a covered aortic stent; there were no differences with regards to TLR at 17 months (i.e., latest available follow up) on univariable analysis (hazard ratio [HR] 1.98, 95% confidence interval [CI] 0.89 – 4.43, p = .095, log rank test).
      Figure 1
      Figure 1Cumulative Kaplan–Meier estimate of freedom from target lesion revascularisation (TLR) during follow up between 102 patients receiving a bare metal aortic stent vs. 150 patients receiving a covered aortic stent for reconstruction of the aortic bifurcation for aorto-iliac occlusive disease. Hazard ratio 1.98, 95% confidence interval 0.89 – 4.43, p = .095.
      The use of a covered aortic stent was not associated with freedom from TLR in a multivariable model in which anatomical parameters that may influence patency were accounted for (Table 4; HR 1.44, p = .42); however, in a subsequent conditional Cox regression (where all variables which differed between the two groups were entered), the use of a covered aortic stent alongside covered common iliac stents was associated with improved freedom from TLR (Table 4). Common femoral endarterectomy was not associated with improved TLR (HR 1.02, p = .83).
      Table 4Multivariable analyses assessing the association between use of covered (n = 150) vs. bare metal (n = 102) aortic stent(s) and target lesion revascularisation (TLR) during follow up in 252 patients with reconstruction of the aortic bifurcation with bare metal or covered stents for aorto-iliac occlusive disease
      HR (95% CI)p value
      Cox regression using anatomical characteristics
       Covered aortic stent1.441 (0.589–3.527).42
       Aortic chronic total occlusion1.498 (0.576–3.895).40
       Iliac chronic total occlusion1.710 (0.579–5.049).33
       Aortic lesion length1.002 (0.988–1.016).78
       Total iliac lesion length1.001 (0.996–1.006).61
       TASC II classification1.877 (0.746–4.718).18
       Severe aortic calcification1.144 (0.231–5.670).86
       Severe iliac calcification1.085 (0.260–4.525).91
      Conditional Cox regression (best fit model)
      R2 (Cox & Snell) 0.56, degrees of freedom 4, p =.048.
       Covered aortic stent0.302 (0.105–0.875).027
       TASC II classification2.184 (0.984–4.848).050
       Use covered common iliac stents0.080 (0.022–0.271).001
      HR = hazard ratio; CI = confidence interval; TASC = Trans-Atlantic Society Consensus.
      R2 (Cox & Snell) 0.56, degrees of freedom 4, p =.048.
      Three (1%) patients underwent a major lower limb amputation after the 30th post-operative day (all with a covered aortic stent) and a total of 28 (11%) patients experienced a MACCE after the 30th post-operative day (10 [10%] with a bare metal aortic stent vs. 18 [12%] with a covered aortic stent, p = .61) (Supplementary Fig. S3). Finally, eight (3%) patients required surgical conversion after the 30th post-operative day (three [3%] with bare metal stents vs. five [8%] with a covered stent, p = .36] (Supplementary Fig. S4). Conversion to open surgery was included in the regression modelling.

      Discussion

      This is the largest multicentre study comparing outcomes of complex endovascular aorto-iliac reconstruction using covered vs. bare metal aortic stents. The study showed that both approaches have satisfactory early and medium term outcomes; however, the use of covered aortic stents was associated with improved freedom from TLR when combined with common iliac covered stenting.
      Endovascular treatment of severe AIOD has evolved considerably with the evolution of iliac stenting techniques.
      • Scheinert D.
      • Schroder M.
      • Balzer J.O.
      • Steinkamp H.
      • Biamino G.
      Stent-supported reconstruction of the aortoiliac bifurcation with the kissing balloon technique.
      Kissing iliac stents are associated with acceptable patency rates, comparable in some cases with open surgery; however, no high quality randomised controlled trials comparing open vs. endovascular AIOD reconstructions are available.
      • Chiu K.W.
      • Davies R.S.
      • Nightingale P.G.
      • Bradbury A.W.
      • Adam D.J.
      Review of direct anatomical open surgical management of atherosclerotic aorto-iliac occlusive disease.
      ,
      • Shen C.
      • Zhang Y.
      • Qu C.
      • Fang J.
      • Liu X.
      • Teng L.
      Outcomes of total aortoiliac revascularization for TASC-II C&D lesion with kissing self-expanding covered stents.
      Furthermore, a variety of novel endovascular therapeutic approaches have been reported for AIOD, involving the use of both covered and bare metal stents in the aorta or iliacs. The Covered vs. Balloon Expandable Stent Trial (COBEST) is the only randomised trial in this area; COBEST showed a benefit when a covered stent was used in TASC II C or D iliac lesions compared with bare metal stents in terms of patency.
      • Mwipatayi B.P.
      • Sharma S.
      • Daneshmand A.
      • Thomas S.D.
      • Vijayan V.
      • Altaf N.
      • et al.
      Durability of the balloon-expandable covered versus bare-metal stents in the Covered versus Balloon Expandable Stent Trial (COBEST) for the treatment of aortoiliac occlusive disease.
      ,
      • Mwipatayi B.P.
      • Thomas S.
      • Wong J.
      • Temple S.E.
      • Vijayan V.
      • Jackson M.
      • et al.
      A comparison of covered vs bare expandable stents for the treatment of aortoiliac occlusive disease.
      However, the study only evaluated the performance of iliac scaffolds.
      Various parameters may influence patency when treating severe AIOD by endovascular means, including stent positioning, stent design and the discrepancy between the stented lumen and aortic lumen or “radial mismatch”.
      • Goverde P.C.
      • Grimme F.A.
      • Verbruggen P.J.
      • Reijnen M.M.
      Covered endovascular reconstruction of aortic bifurcation (CERAB) technique: a new approach in treating extensive aortoiliac occlusive disease.
      ,
      • Kavaliauskiene Z.
      • Antusevas A.
      • Kaupas R.S.
      • Aleksynas N.
      Recent advances in endovascular treatment of aortoiliac occlusive disease.
      ,
      • Mwipatayi B.P.
      • Sharma S.
      • Daneshmand A.
      • Thomas S.D.
      • Vijayan V.
      • Altaf N.
      • et al.
      Durability of the balloon-expandable covered versus bare-metal stents in the Covered versus Balloon Expandable Stent Trial (COBEST) for the treatment of aortoiliac occlusive disease.
      The latter might cause flow disturbances and thrombus formation. Choosing a configuration with the lowest radial mismatch is the hypothesis that led to the advent of the Covered Endovascular Repair of the Aortic Bifurcation (CERAB) technique, which aims to achieve a more “anatomical” distal aortic reconstruction with three covered stents.
      • Grimme F.A.
      • Goverde P.C.
      • Verbruggen P.J.
      • Zeebregts C.J.
      • Reijnen M.M.
      Editor's Choice - First results of the covered endovascular reconstruction of the aortic bifurcation (CERAB) technique for aortoiliac occlusive disease.
      ,
      • Goverde P.C.
      • Grimme F.A.
      • Verbruggen P.J.
      • Reijnen M.M.
      Covered endovascular reconstruction of aortic bifurcation (CERAB) technique: a new approach in treating extensive aortoiliac occlusive disease.
      ,
      • Taeymans K.
      • Goverde P.
      • Lauwers K.
      • Verbruggen P.
      The CERAB technique: tips, tricks and results.
      To date, results from CERAB series up to three years have demonstrated acceptable results.
      • Grimme F.A.
      • Goverde P.C.
      • Verbruggen P.J.
      • Zeebregts C.J.
      • Reijnen M.M.
      Editor's Choice - First results of the covered endovascular reconstruction of the aortic bifurcation (CERAB) technique for aortoiliac occlusive disease.
      ,
      • Goverde P.C.
      • Grimme F.A.
      • Verbruggen P.J.
      • Reijnen M.M.
      Covered endovascular reconstruction of aortic bifurcation (CERAB) technique: a new approach in treating extensive aortoiliac occlusive disease.
      ,
      • Taeymans K.
      • Goverde P.
      • Lauwers K.
      • Verbruggen P.
      The CERAB technique: tips, tricks and results.
      These come from the high volume institutions that reported the technique originally. The currently available CERAB studies and those relating to other similar techniques published to date have a number of limitations. They are mostly single centre cohort studies from high volume experienced centres with relatively limited follow up. Results have not been replicated in non-tertiary centres, and longer term outcomes are lacking. Additionally, the currently available endovascular literature in AIOD has not quantified the degree of calcium in atherosclerotic plaques, and anatomical data are not reported uniformly. A direct comparison between bare metal and covered aortic stents in complex AIOD has also not been attempted.
      This current study represents real world practice from 12 European centres. It also provides outcomes for allcomers who presented with complex severe AIOD. Of note, 32% had aortic CTO, 46% had iliac CTO, and 48% presented with CLTI. These features reflect the extensive AIOD burden in this cohort, as seen in everyday practice. In addition, most patients had severe aortic and/or iliac calcification. This was reflected by the difficulty of the revascularisation procedures, with 56% of patients requiring bilateral femoral access and 13% requiring simultaneous brachial and femoral access with recanalisation achieved via a subintimal plane in 27% of patients. Further, the patients treated had a variety of anatomies and comorbidities. This reflects real world practice; however, it does impact on the validity of the findings. The present authors tried to address this using multivariable regression analyses based on two different models.
      Analysis of midterm outcomes in the current study showed no difference in mortality, TLR, or major amputation between patients with bare metal vs. covered aortic stents. A number of multivariable analyses were performed to adjust for potential confounders and this finding was consistent. The only difference was that covered aortic stents were associated with improved freedom from TLR if combined with covered iliac stents in a multivariable conditional regression. This is in line with the COBEST trial. The present authors appreciate that in this pragmatic multicentre series a number of confounders are present, as expected in any dataset reporting real world data; however, there is definitely no strong signal that uncovered stents are unsafe. These findings should be taken into consideration when planning the reconstruction of severe AIOD. It should be noted that a variety of different covered stents were used, even some designed for endovascular aneurysm repair, indicating the lack of a standardised approach. Also, bare metal stent reconstructions usually require smaller sheaths (5 and 6 French) and could be deployed percutaneously through upper extremity access in patients with hostile distal anatomy. Further, it should be pointed out that covered aortic stents will occlude potential collateral circulation via lumbar arteries or the inferior mesenteric artery, depending on each individual’s anatomy. An interesting finding in this study was that patients with a covered stent spent a longer time in hospital. This might be because more severe anatomies were treated with covered stents or the larger size of the sheaths needed. In this context, the decision between covered and bare metal stents should be made after consideration of various parameters such as lesion morphology (thrombus, calcification) and access. An important issue to take into account when relating the results of this series into clinical practice is that subgroup analyses relating to special stent characteristics (e.g., radial force, stent design, and stent materials) could not be performed. This can only be addressed in a very large pragmatic study. The present authors strongly advocate the creation of multicentre registries and participation in pragmatic randomised trials in this clinical context for the future.

      Limitations

      This study has a number of limitations. It represents a retrospective analysis of prospectively maintained databases, with inherent recall, selection, and reporting bias. Also, even though the study reported the degree of calcification at the level of the aorta and iliac arteries, this was performed by the lead investigator at each institution. It was not possible to validate reporting because of the lack of a core imaging laboratory. The small number of post-operative complications and size of the series does not allow performance of in depth comparative analyses. Further, Kaplan–Meier curves were reported to a maximum of 72 months, given the duration of follow up and number of patients; however, the number of patients at risk at each time interval was reported to ensure the analysis reflects the size of the cohort surviving. Given the size of the study and variability in stents used, comparisons cannot be made between balloon and self expandable stents for common iliac disease / aortic disease, especially of an occlusive nature. Other subgroup analyses, for example relating to the degree of radial force are also not feasible. Also it was not possible to adjust per volume of centre, given the number of centres involved and that the actual volume of patients presenting with AIOD is difficult to report precisely. No core imaging laboratory was used for this series, which might have impacted on uniformity of reporting. Wound, Ischaemia and Foot Infection (WIFI) scores were not documented and hence are not reported. The number of CFA endarterectomies in the covered stent group is substantially higher and may have contributed to a lower TLR rate. An analysis based on propensity scoring is not feasible using this dataset and cohort of patients, because of the number of patients included. Such an approach would limit the number of patients in each arm very considerably. Finally, the registry has not been externally validated.

      Conclusion

      Endovascular AIOD reconstruction has satisfactory 30 day and midterm outcomes despite adverse anatomical and technical features and should be considered in suitable patients. Covered aortic stents might be associated with better freedom from TLR when combined with covered iliac stents. The need for procedural standardisation is crucial and further prospective trials should compare the two treatment strategies.

      Conflict of interest

      S Abisi is a consultant for Bentley InnoMed, Cryolife, and Cook Medical. R Coscas has been consultant for Medtronic Inc., Boston Scientific Inc., Gore Inc., Spectranetics Inc., Biotronik Inc., and Bard Inc. M Ruffino is a consultant for and has received educational grants from Terumo Europe; she is a speaker for Bentley InnoMed, Biotronik, Boston Scientific, Cardiovascular Systems, and Penumbra. A Saratzis is funded by the National Institute of Healthcare Research (NIHR), British Heart Foundation (BHF), and receives honoraria from Amgen Inc., Regeneron Inc., and Abbott Medical Ltd. K Stavroulakis consults for Phillips, Shockwave, Terumo, and received honoraria from Medtronic Inc., Boston Scientific Inc., and Biotronik Inc. I Van Herzeele is a consultant for Medtronic Inc. H Zayed has received research grants from Abbott Medical and is a speaker for Abbott, Boston Scientific, Gore Medical, Cryolife, Bentley InnoMed, and Cook Medical. The rest of the authors have no interest to declare.

      Funding

      None.

      Acknowledgements

      The authors would like to acknowledge the contribution of the following colleagues: Morad Sallam, Tommaso Donati, Sanjay Patel, Lukla Biasi, Narayanan Thulasidasan, Tarun Sabharwal, Athanasios Diamantopolous, Ashish Patel, Rebecca Sandford, Bijan Modarai, Stephen Black, Michael Dialynas, Mark Tyrrell, Talia Lea, Gianluca Faggioli, and Enrico Gallitto.

      Appendix A. Supplementary data

      Supplementary Figure S1
      Supplementary Figure S2
      Supplementary Figure S2Kaplan Meier curve comparing survival during follow-up between patients receiving a bare metal aortic stent (Group A, n=102) vs. patients receiving a covered aortic stent (Group B, n=150).
      Supplementary Figure S3
      Supplementary Figure S3Kaplan Meier curve comparing freedom from major adverse cardiac events during follow-up between patients receiving a bare metal aortic stent (Group A, n=102) vs. patients receiving a covered aortic stent (Group B, n=150).
      Supplementary Figure S4
      Supplementary Figure S4Kaplan Meier curve comparing freedom from surgical conversion during follow up between patients receiving a bare metal aortic stent (Group A, n = 102) vs. patients receiving a covered aortic stent (Group B, n = 150).

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