Randomised Controlled Trial of Adjuvant Photodynamic Therapy to Reduce Restenosis After Percutaneous Transluminal Angioplasty to the Superficial Femoral Angioplasty

Background:

Percutaneous Transluminal Angioplasty (PTA) is well recognised as a treatment for obstructive vascular disease. Despite an initial high procedural success the technique is limited by the subsequent development of restenosis in up to 50% of patients between 3 and 6 months. ,

The pathological hallmark of restenosis has long been considered to be the development of neointimal hyperplasia consisting of smooth muscle cells and extracellular matrix. We now realise however that both elastic recoil of the vessel and the concept of remodelling are important in determining the overall response of the vessel to injury. Remodelling involves a geometric change in the vessel such that the maximum arterial dimension may increase (positive remodelling) or decrease (negative remodelling). , ,

Despite extensive research no pharmacological or interventional strategy has been shown to have an overwhelming effect on restenosis rates after angioplasty. Recently attention has been focused on the potential of intraluminal radiation therapy (Brachytherapy) and whilst this technique has shown considerable promise there are concerns regarding the long term complications and safety of the ionising radiation for non-malignant disease with reports of vessel wall damage after treatment. ,

Photodynamic therapy is a novel technique that involves the activation of a previously administered photosensitising agent by non thermal laser light. This results in the generation of reactive oxidative products with resulting tissue effects. It is a technique that has been used in the treatment of a variety of malignancies but the realisation that it may influence the response of the vessel wall after balloon injury has been particularly promising. 5 Aminolaevulinic acid (ALA) is a relatively new photosensitising agent which is converted to an active metabolite, Protoporphyrin IX (PPIX) in the biosynthesis of haem. In small animal models photodynamic therapy has been shown to cause medial smooth muscle cell depletion and to reduce the degree of neointimal hyperplasia after injury with no detrimental effects on the mechanical integrity of the vessel wall. , Large animal work using a swine model has confirmed these findings and has also demonstrated that favourable vessel wall remodelling occurs after PDT. Repopulation of the media with smooth muscle cells, after early depletion, has also been demonstrated which is likely to be important when we consider the long term effects of this treatment on the vessel wall.