Predictors of Major Adverse Limb Events After Endovascular Iliac Stenting: a Real-world Cohort Study (PREMISE-ILIAC)

Predictors of Major Adverse Limb Events After Endovascular Iliac Stenting: a Real-world Cohort Study (PREMISE-ILIAC Study)

Peripheral arterial disease involving the iliac arteries is a common manifestation of systemic atherosclerosis and a major cause of lifestyle-limiting claudication and chronic limb-threatening ischemia. Endovascular iliac artery stenting has become the preferred treatment strategy for most iliac lesions, including complex TransAtlantic Inter-Society Consensus II (TASC II) C and D lesions, owing to high technical success rates and lower perioperative morbidity compared with open surgical reconstruction.

Despite widespread adoption of endovascular treatment, available evidence regarding predictors of major adverse limb events (MALE) after iliac artery stenting remains limited, particularly in unselected real-world populations with substantial comorbidity burden. Patient-related factors, including frailty, may contribute to post-procedural outcomes in addition to lesion-related characteristics.

This retrospective single-center cohort study will evaluate clinical outcomes following endovascular iliac artery stenting in consecutive adult patients treated at IRCCS Galeazzi-Sant'Ambrogio Hospital, Milan, Italy. The study will assess the occurrence of major adverse limb events (MALE), primary patency, peri-procedural complications, target lesion revascularization, restenosis or occlusion, and all-cause mortality. Clinical, anatomical, and procedural factors associated with adverse limb outcomes, including frailty assessed by the modified five-item Frailty Index (mFI-5), will also be investigated.

Study Overview

• Status: Recruiting
• Conditions: Peripheral Arterial Disease; Intermittent Claudication; Aortoiliac Occlusive Disease; Chronic Limb-Threatening Ischemia
• Intervention / Treatment: Procedure: Iliac stenting

Detailed Description

Peripheral arterial disease (PAD) involving the iliac arteries is a common manifestation of systemic atherosclerosis and represents a frequent cause of lifestyle-limiting intermittent claudication and chronic limb-threatening ischemia (CLTI). Over the past two decades, continuous advances in endovascular techniques, stent technology, and peri-procedural imaging have led to a progressive shift from open surgical reconstruction toward an endovascular-first strategy for the treatment of aortoiliac occlusive disease, including anatomically complex lesions classified as TransAtlantic Inter-Society Consensus II (TASC II) C and D.

Current international guidelines support endovascular treatment for most iliac lesions because of high technical success rates and lower perioperative morbidity compared with open surgical reconstruction. As a result, iliac artery stenting has become the predominant treatment modality in routine vascular practice. However, much of the available evidence is derived from selected patient populations or controlled clinical studies and may not fully reflect outcomes observed in unselected real-world cohorts with substantial comorbidity burden.

Although procedural success and vessel patency after iliac artery stenting have been widely reported, less information is available regarding predictors of clinically meaningful limb-related outcomes, particularly Major Adverse Limb Events (MALE). Furthermore, lesion morphology alone may not adequately explain variability in outcomes after technically successful revascularization. Patient-related factors, including frailty, chronic kidney disease, diabetes mellitus, coronary artery disease, and advanced age, may significantly influence post-procedural clinical trajectories. Frailty, assessed using the modified five-item Frailty Index (mFI-5), has been associated with adverse outcomes in cardiovascular and vascular surgical populations, but its prognostic role in patients undergoing iliac artery stenting remains insufficiently characterized.

This study is a single-center retrospective observational cohort study conducted at the Division of Vascular Surgery, IRCCS Galeazzi-Sant'Ambrogio Hospital, Milan, Italy. Consecutive adult patients who underwent endovascular stenting for de novo stenotic or occlusive disease of the common and/or external iliac arteries between January 2023 and May 2025 will be included. Clinical, anatomical, procedural, and follow-up data will be retrospectively extracted from institutional vascular registries, imaging databases, and electronic medical records.

The primary objective is to evaluate MALE-free survival following endovascular iliac artery stenting. Secondary objectives include assessment of primary patency, peri-procedural complications, target lesion revascularization, restenosis or occlusion, and all-cause mortality. The study will also evaluate associations between baseline clinical and anatomical characteristics and adverse limb outcomes, with particular attention to frailty as assessed by the mFI-5.

Follow-up data are derived exclusively from routine clinical surveillance, including outpatient evaluations, ankle-brachial index measurements when available, duplex ultrasound examinations, and additional imaging studies performed according to clinical indications. Outcomes will be analyzed using Kaplan-Meier survival methods and Cox proportional hazards regression models to identify factors associated with adverse clinical outcomes after iliac artery stenting in a real-world population.

• Study Type: Observational
• Enrollment (Estimated): 98

Contacts and Locations

• Study Contact: Name: Luca Galassi, MD; Phone Number: +393458013083; Email: luca.galassi@unimi.it

Study Locations

• Italy
  • Mi
    • Milan, Mi, Italy, 20157
      • Recruiting
      • IRCCS Galeazzi Sant'Ambrogio Hospital
      • Contact: Elena Cittera Dr.; Phone Number: +390283502224; Email: direzionescientifica.ogsa@grupposandonato.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Consecutive adult patients (≥18 years), both male and female, undergoing endovascular stenting for stenotic or occlusive disease of the common and/or external iliac arteries (CIA/EIA) at IRCCS Galeazzi-Sant'Ambrogio, Milan, between January 2023 and May 2025, will be retrospectively included. Lesions will be classified according to TASC II, with an expected predominance (~70%) of complex (C-D) lesions.

Description

Inclusion Criteria:

Adult patients aged ≥18 years, of both male and female sex

• Presence of haemodynamically significant stenosis or occlusion of the common iliac artery (CIA) and/or external iliac artery (EIA), documented by computed tomography angiography, magnetic resonance angiography, or diagnostic angiography
• Symptomatic peripheral artery disease, including lifestyle-limiting intermittent claudication (Rutherford category 2-3) or chronic limb- threatening ischaemia (CLTI; Rutherford category 4-6), refractory to optimal medical therapy
• Treatment with endovascular iliac artery stenting (covered or uncovered; balloon-expandable or self-expanding devices) as the primary revascularisation strategy
• De novo iliac lesions only
• Availability of complet

Exclusion Criteria:

Primary open surgical revascularisation of the iliac axis (e.g., aorto- bifemoral bypass or endarterectomy).

• Previous stenting of the target iliac segment (in-stent restenosis cases excluded).
• Aorto-iliac aneurysmal disease as the primary indication for treatment (including EVAR or fenestrated endografts).
• Hybrid procedures with concomitant infrainguinal bypass surgery.
• Incomplete clinical, procedural, or follow-up data preventing assessment of study endpoints.
• Loss to follow-up without documented clinical outcomes.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Experiencing Major Adverse Limb Events (MALE) Within 12 Months	MALE is defined as a composite endpoint including: acute limb ischaemia requiring intervention, major amputation (above or below knee), or surgical/endovascular re-intervention on the target iliac vessel. Results will be reported as the number and proportion of participants experiencing at least one MALE event within 12 months of the index procedure. Independent predictors will be identified by multivariable Cox regression, including frailty (mFI-5), lesion complexity (TASC II class), stent type, and cardiovascular comorbidities.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary Patency of the Treated Iliac Artery Segment	Primary patency defined as freedom from target lesion revascularization and absence of documented iliac artery occlusion during follow-up, assessed by duplex ultrasound or cross-sectional imaging.	12 months
Number of Participants With Peri-Procedural Complications	Number of participants experiencing peri-procedural complications within 30 days after iliac stenting, including access-site complications, arterial dissection, perforation, pseudoaneurysm, hematoma formation, contrast-induced nephropathy, hemorrhagic events, and neurological events.	30 days
All-Cause Mortality	Number of participants who die from any cause following the index iliac stenting procedure.	12 months
Freedom From Target Lesion Revascularization (TLR)	Time from the index procedure to the first repeat endovascular or surgical intervention performed on the treated iliac artery segment	12 months
Number of Participants With Iliac Artery Restenosis or Occlusion	Number of participants with documented restenosis or occlusion of the treated iliac artery segment detected by duplex ultrasound, computed tomography angiography, or other clinically indicated imaging.	12 months

Collaborators and Investigators

• Sponsor: I.R.C.C.S Ospedale Galeazzi-Sant'Ambrogio

Study record dates

Study Major Dates

• Study Start (Actual): June 16, 2026
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 16, 2026

Study Registration Dates

• First Submitted: June 17, 2026
• First Submitted That Met QC Criteria: June 23, 2026
• First Posted (Actual): June 26, 2026

Study Record Updates

• Last Update Posted (Actual): June 26, 2026
• Last Update Submitted That Met QC Criteria: June 23, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Peripheral Arterial Disease; Iliac Artery Stenting; Endovascular Revascularization
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Chronic Disease; Disease Attributes; Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Peripheral Vascular Diseases; Ischemia; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Chronic Limb-Threatening Ischemia; Peripheral Arterial Disease; Intermittent Claudication
• Other Study ID Numbers: PREMISE-ILIAC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No