Minimally invasive treatment of the iliac artery

Peripheral artery disease (PAD) is caused by atherosclerotic stenoses or occlusions of the lower limb and leads to intermittent claudication and chronic limb threatening ischemia (CLTI). When PAD is located in the aortoiliac segments, it is termed AIOD (Aortoiliac Occlusive Disease). All patients with PAD should receive intensive risk factor modification, both through life style modification and medical therapy. For patients with claudication, supervised exercise therapy (SET) is the first treatment step. When disabling symptoms persist after SET, and for patients with CLTI, revascularization is warranted.
When considering revascularization there are, generally speaking, two options: Surgical or endovascular. In general, surgical repair has higher patency rates, but comes with higher morbidity, mortality and longer hospital stay. Endovascular repair has lower patency rates and, in the past, was considered unsuitable for more advanced lesions. Nowadays, indications have broadened and most physicians advocate an ‘endovascular first’ strategy for all lesions, but patency rates are still lower than for surgical repair. For some indications, hybrid procedures are available, combining some of the benefits of both open and endovascular procedures.
In this thesis several endovascular and hybrid techniques and strategies for treating iliac artery disease have been studied.
Chapter 2 is a Cochrane systematic review comparing primary stenting with percutaneous transluminal angioplasty (PTA) with selective stenting. In the first technique a stent is placed in all patients, in the second technique a stent is only placed when there is an unsatisfactory result after PTA. Two randomized controlled trials (RCT) could be included, with a total of 397 participants. Due to heterogeneity in baseline characteristics and outcome definitions, results could not be pooled. One RCT which included only iliac occlusions found significantly more immediate complications in the PTA group, mainly distal embolization. For the other primary outcomes, technical success, patency and symptomatic improvement, no differences were found between both groups.
Chapter 3 is a review of the literature on self-expanding stents for AIOD. The biomechanical properties of self-expanding stents would make them more suitable for tortuous arteries which are susceptible to flection during body movement, whereas balloon expandable stents would be more suitable for heavily calcified lesions and when precise placement is necessary. The level of evidence for this assumption is low, level 4 according to the Oxford Centre for Evidence Based Medicine.
Chapter 4 is a systematic review and meta-analysis of the use of covered stents for AIOD. A total of 19 studies were identified, 12 single-arm studies including 826 limbs, and 7 series comparing covered stents to bare-metal stents, including 1126 limbs. Four more series described bifurcated reconstructions with covered stents; 3 series on EVAR (EndoVascular Aneurysm Repair) stentgrafts and 1 series on CERAB (Complete Endovascular Repair of the Aortic Bifurcation). Meta-analysis of the comparative series showed no benefit of covered stents over bare-metal stents with regard to technical success, complications, primary or secondary patency. Studies looking specifically at more advanced lesions (TASC C and D) did show a benefit for covered stents, however due to the heterogeneity of the TASC II classification, it was not possible to identify which specific lesions might benefit from covered stents. The series on bifurcated reconstructions showed excellent results given that this was a subset of patients with more advanced disease, but no randomized or comparative retrospective cohort studies were available.
Chapter 5 is the study protocol for the Dutch Iliac Stent trial: COVERed balloon-expandable versus uncovered balloon-expandable stents in the common iliac artery (DISCOVER). In this randomized, controlled, double-blind, multicenter trial 174 patients were included with advanced atherosclerotic lesions of the common iliac artery (CIA) and treated with either covered or uncovered stents. An advanced lesion was defined as either an occlusion, or a stenosis longer than 3 cm. Additional treatment of any lesions in the aorta, external iliac artery and common femoral artery was mandatory, to guarantee optimal inflow and outflow through at least a patent deep or superficial femoral artery. Additionally, scrupulous verification of technical success had to be performed using digital subtraction angiography in two perpendicular directions, and intra-arterial translesional pressure gradient measurement. Patients were followed up for 2 years, and the primary end point was freedom from restenosis rate.
Chapter 6 describes the final results of the DISCOVER trial. Patients were included from 2012 until 2019. Technical success was achieved in all patients. Complete follow-up data at 2 years was available for 89.7% of patients, owing to six patients who had died during follow-up and 12 patients who were lost to follow-up. Freedom from restenosis rates after 2 years of follow-up were not different between both groups, 84.7% (95% confidence interval (CI) 76.7%–92.7%) in the uncovered stent group and 89.1% (95% CI 82.4%–95.8%) in the covered stent group (p=0.40). Freedom from occlusion was 95.0% (95% CI 90.3%–95.7%) in the covered stent group and 96.4% (95% CI 92.5%–100%) in the uncovered stent group (p=0.66). Freedom from target lesion revascularization was 91.1% (95% CI 84.8%–97.3%) and 95.2% (95% CI 90.7%–99.7%), respectively (p=0.31). Complications, mortality, clinical success and hemodynamic success were also comparable between both groups. Per-protocol analysis did not affect the outcomes of the study. Subgroup analysis did not identify any subgroups in which either stent performed better than the other. There were some limitations to this study. It took 7 years to include all 174 patients, where two years were anticipated. There were more patients who received kissing stents in the covered stent group than in the uncovered stent group, despite randomization. No explanation was found for difference. Additional subgroup analysis and multivariable modelling showed no influence of this imbalance on the results of the study. So, based on the results of this study, routine use of covered stents for advanced lesions of the common iliac artery cannot be advocated.
Chapter 7 is a retrospective series comparing angioplasty and repeated stenting with a covered stent in patients with common iliac artery in-stent restenosis (CIA-ISR). Between 2007 and 2017, 74 interventions were included, 37 in each group. Freedom from restenosis after the reintervention was 72.6% in the patients treated with a covered stent and 43.5% in the patients treated with angioplasty alone after 4 years of follow-up (p=0.003). There were also significantly more reinterventions in this group (43.6%) compared with the group of patients who had received a covered stent (16.4%, 0=0.020). Based on these results and until further evidence is available, patients with CIA-ISR should be treated with a covered stent rather than angioplasty alone.
Chapter 8 is a retrospective series of patients who underwent remote iliac artery endarterectomy (RIAE) in two vascular centers between 2004 and 2015. Technical success was 84.7%, but most patients with a technical failure could be successfully treated with a bail-out procedure, which did not negatively influence long term outcomes. Complication rate was 13.7%, and 30-day mortality rate was 0%. Primary patency at 5 years was 78.2%, and secondary patency was 86.7% (number at risk 10). It appears RIAE is a viable treatment option for selected patients with combined common femoral artery (CFA) and iliac lesions. It offers higher patency rates than hybrid treatment with CFA endarterectomy and endovascular treatment of the iliac arteries, and lower morbidity and mortality rates than open surgical bypass.
Chapter 9 is a retrospective series of patients treated with the Cook Zenith ZBIS iliac branch device (IBD), including 162 IBD implantations in 7 vascular centers between 2004 and 2015. Technical success was achieved in 157 procedures (96.9%). In 15 patients (9.3%) there was an occlusion of the internal iliac artery branch, either perioperatively or during follow-up. Six of these patients (40%) developed buttock claudication. Freedom from secondary intervention was 75.9% at 5 years. These results show that treatment of the common iliac artery with an iliac branch device is a safe and feasible option, however efforts should be made to reduce reintervention rates and internal iliac branch occlusion rates.