title: Current Phase II drugs under investigation for the treatment of limb ischemia.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors: a 1 Patras University Hospital, Department of Interventional Radiology , Patras 26504, Greece +30 2613 603 219; stavspiliop@upatras.gr.
authors: Stavros
authors: S
authors: Spiliopoulos
authors: a 1 Patras University Hospital, Department of Interventional Radiology , Patras 26504, Greece +30 2613 603 219; stavspiliop@upatras.gr.
authors: Panagiotis
authors: P
authors: Kitrou
authors: b 2 Guy's and St Thomas' Hospitals, NHS Foundation Trust, Department of Interventional Radiology , London, UK.
authors: Konstantinos
authors: K
authors: Katsanos
authors: a 1 Patras University Hospital, Department of Interventional Radiology , Patras 26504, Greece +30 2613 603 219; stavspiliop@upatras.gr.
authors: Dimitris
authors: D
authors: Karnabatidis
mesh_terms: D000818:Animals; D017322:Clinical Trials, Phase II as Topic; D016503:Drug Delivery Systems; D015195:Drug Design; D015507:Drugs, Investigational / Q000008:administration & dosage / Q000494:pharmacology; D057510:Endovascular Procedures / Q000379:methods; D006801:Humans; D007511:Ischemia / Q000209:etiology / Q000503:physiopathology / Q000628:therapy*; D023821:Limb Salvage / Q000379:methods*; D058729:Peripheral Arterial Disease / Q000150:complications / Q000628:therapy*; D012307:Risk Factors
chemical_list: D015507:Drugs, Investigational
keywords: Phase II trials; critical limb ischemia; drug therapy; drug-coated balloons; drug-eluting stents; endovascualar treatment; therapeutic angiogenesis