Intravascular Ultrasound for Endovascular Revascularization in Peripheral Artery Disease

Introduction Although angiography-guided endovascular revascularization is a key treatment modality for symptomatic PAD management, limb outcomes remain poor, particularly in chronic limb-threatening ischemia (CLTI). Intravascular ultrasound (IVUS) provides high-resolution intraluminal imaging and has demonstrated benefit in coronary interventions, but its role in PAD revascularization remains uncertain. This thesis evaluates IVUS in PAD using complementary methodological approaches. Methods First, a systematic review and meta-analysis of randomized controlled trials and observational studies was conducted to compare IVUS-guided and angiography-guided PAD endovascular revascularization. Randomized evidence suggests that IVUS guidance likely reduces restenosis, although its effects on reintervention, major amputation, and mortality remain uncertain. Observational studies demonstrate consistent associations between IVUS use and improved outcomes; however, these findings are limited by low certainty of evidence due to potential bias and confounding. Second, an international, multidisciplinary survey of clinicians involved in CLTI revascularization demonstrated substantial heterogeneity in IVUS utilization, identified key barriers to its adoption, and confirmed persistent clinical equipoise and willingness to randomize in a large trial comparing IVUS with angiography. Third, CLARITY is a multicenter randomized trial comparing IVUS-guided versus angiography-guided revascularization in patients with CLTI and ≥70% infrainguinal stenosis. After successful wire crossing, patients are randomized 1:1 to IVUS-guided optimization or standard angiographic guidance. The primary endpoint is a composite of major adverse limb events or restenosis over a median follow-up of 3 years. An initial Vanguard Phase will assess feasibility before Full Trial expansion. Given the ongoing nature of the trial, outcome data from CLARITY are not included in this thesis. Conclusions This work aims to address a critical evidence gap in PAD management. While IVUS shows promise in reducing restenosis, definitive evidence regarding its impact on hard clinical outcomes is lacking. The CLARITY research program is positioned to provide robust evidence to inform clinical practice and guideline recommendations.