Current Phase II drugs under investigation for the treatment of limb ischemia.

INTRODUCTION: More than 20 million people in Europe suffer from peripheral arterial disease and nearly 3% develop critical limb ischemia (CLI). Without any medical treatment, CLI has poor prognosis, resulting in limb loss and high mortality rate. Until today, no systemic drug is available for the treatment of CLI and the gold standard method of treatment includes risk factor modification and open surgical or endovascular revascularization. Endovascular local drug delivery devices and novel antithrombotic agents, currently under investigation, aim to improve outcomes of revascularization procedures. The pioneering concept of therapeutic angiogenesis induced by gene and stem cell therapy has been proposed, in an attempt to increase ischemic tissue perfusion.

AREAS COVERED: This review summarizes local and systemic pharmacological treatment of CLI using endovascular or pharmaco-biological therapy and focuses on Phase II trials available for these drugs.

EXPERT OPINION: Novel endovascular technologies combining angioplasty and local drug-delivery continuously improve and will come to be standard of practice for the management of limb ischemia, while new antithrombotic agents will further improve outcomes. Therapeutic angiogenesis represents a safe and promising treatment option. The combination of revascularization with microcirculation improvement induced by gene or stem cell therapy could enhance limb salvage.