100 QUESTIONS IN CARDIOLOGY

24 What new approaches are there to prevent

restenosis following PTCA?

Richard Mansfield

Percutaneous transluminal coronary angioplasty (PTCA) is a

well-established treatment for patients with coronary artery

disease. However, the excellent initial procedural outcome is

limited by the late development of restenosis occurring in

approximately 30% of cases between 3 and 6 months. The

introduction of intracoronary stents, which now account for more

than 70% of all interventional procedures has had only a modest

effect on restenosis rates. There were over 20,000 angioplasty or

related procedures in the UK in 1996 and it is easy to appreciate

the clinical and economic burden of restenosis.

Pharmacological approaches

To date no pharmacological agent has had a significant effect on

reducing the incidence of restenosis. There are a number of

reasons for this including the lack of correlation between animal

models and the situation in man, the drug doses used or the

power of some of the trials. Recent interest has focused on the use

of antiproliferative agents such as paclitaxel and tranilast.

The antioxidant Probucol has been shown to be effective in

limiting restenosis after balloon angioplasty. However, lack of

licensing in some countries, limited data on the clinical impact of

treatment, and the fact that pre-treatment for 4 weeks is required,

may all be factors in limiting its use.

Gene therapy involves the transfer of DNA into host cells with

the aim of inducing specific biological effects. Vectors for gene

delivery include plasmid DNA-liposome complexes and viral

vectors such as the replication deficient recombinant adenovirus.

Design of appropriate delivery devices has taken a number of

directions including double balloon catheters and perforated

balloons allowing high pressure injection through radial pores.

Various approaches have been used to limit experimental

restenosis by inducing cell death (e.g. fas ligand gene to induce

apoptosis), inhibiting smooth muscle cell migration (e.g. over-

expression of TIMP-1 and eNOS) or by inhibiting cell cycle

regulators of smooth muscle cell proliferation (e.g. antisense