Critical Limb Ischaemia: Pathophysiology, Diagnosis, and Contemporary Management Strategies: A Critical Review

Abstract

Critical limb ischaemia (CLI), increasingly designated chronic limb-threatening ischaemia (CLTI) in contemporary vascular practice, represents the most severe manifestation of peripheral arterial disease and constitutes one of the foremost challenges in modern vascular medicine. Characterised by ischaemic rest pain, non-healing ulceration, and tissue gangrene attributable to chronic arterial insufficiency, CLI carries a one-year mortality rate approaching 20–25% and a risk of major amputation of comparable magnitude in the absence of timely and effective intervention. Despite considerable advances in both endovascular and open surgical techniques over the past two decades, outcomes remain disconcertingly poor, and a substantial proportion of patients continue to receive care that falls short of established guideline recommendations. This critical review synthesises evidence from peer-reviewed journals published between January 2000 and February 2026, encompassing the epidemiology, pathophysiology, diagnostic strategies, medical management, revascularisation options, and emerging therapies relevant to CLI. The landmark BASIL, BEST-CLI, and BASIL-2 randomised controlled trials are critically appraised alongside major guideline frameworks from the Global Vascular Guidelines, the European Society of Cardiology, and the American Heart Association/American College of Cardiology. The emerging controversy surrounding paclitaxel-coated devices, the evolving role of antithrombotic therapy, and advances in biological and regenerative medicine for patients lacking conventional revascularisation options are also examined. The review concludes that whilst revascularisation — particularly open bypass surgery in patients with adequate saphenous vein — remains the cornerstone of CLI management, a holistic, multidisciplinary approach integrating optimal medical therapy, structured wound care, and carefully selected emerging biological strategies is essential to improving both limb salvage and long-term survival in this high-risk patient population.