Restenosis remains a major problem after percutaneous coronary intervention. Reported rates are as high as 50%, depending on specific lesion and patient subset. Investigators continue to explore new strategies that may be effective in preventing restenosis.

Dr. Holmes reported on the largest-ever interventional trial for prevention of restenosis. This trial, which included 11,500 patients from many different countries, is known as PRESTO (Prevention of Restenosis with Tranilast and its Outcomes).

Preclinical models show that tranilast reduces intimal hyperplasia and vascular smooth muscle cell migration. Small pilot studies in humans suggest the drug is dramatically effective in reducing rate of restenosis after balloon angioplasty, stenting and directional atherectomy.

Based on that evidence, investigators randomized a large group of patients to placebo or tranilast in a low or high dose, administered for one or three months. The main requirement for study entry was a successful percutaneous coronary intervention. About half of the patients had unstable angina, while 25% had diabetes. Many had severe lesions and some had chronic total occlusions.

The primary endpoint of the study was incidence of major adverse cardiac events (all-cause mortality, myocardial infarction, and ischemia-driven target vessel revascularization) at nine months. Investigators anticipated a 30% reduction in major adverse cardiac events as clinically relevant. However, cumulative risk for events was identical for the placebo group and the four tranilast groups, ranging from 15.4% to 16%.

Tranilast treatment did not result in less restenosis. In an angiographic substudy including more than 2,000 patients, the restenosis rate ranged from 32% to 35%. Myocardial infarction occurred in 1.4% of patients and death in 1.2% during the 9 months of the study.

While these results were disappointing, Dr. Holmes said the trial provides researchers with an unprecedented library of data reflecting the current practice of interventional cardiology. The sponsor of this trial has encouraged the investigators to look at subsets of patients as the basis for identifying new treatment strategies.

Because trial enrollment was very rapid (approximately 1,000 patients per month), the database gives a detailed overview of the practice of interventional cardiology over the past 1? years.

Perhaps tranilast will work better using a local drug delivery strategy. According to Dr. Holmes, that is the subject of a Japanese study, which will probably be conducted soon.