AGI-1067: a novel vascular protectant for prevention of restenosis.

Objective: To review the synthesis, pharmacology, clinical trials, and adverse effects of AGI-1067, a novel agent for preventing restenosis.

Data Sources: Literature searches were conducted using MEDLINE (1966-July 2005) and International Pharmaceutical Abstracts (1970-July 2005) for English-language articles containing the search terms AGI-1067, AGI 1067, and probucol. In addition, bibliographies from relevant articles were reviewed for additional references.

Study Selection And Data Extraction: All articles identified from data sources were reviewed for relevant information. Applicable information was included in this review.

Data Synthesis: AGI-1067, a derivative of the lipid-lowering agent probucol, is the first of a new class of drugs termed vascular protectants. It has antioxidant and lipid-lowering effects. In addition, it inhibits inflammatory processes without resultant immunosuppression through its selective inhibition of vascular cell adhesion molecule-1 expression. AGI-1067 also exhibited anti-atherosclerotic effects in preclinical studies. Relatively short-term treatment with AGI-1067 showed positive results compared with probucol in preventing restenosis in patients undergoing percutaneous coronary intervention. AGI-1067 appears to be well tolerated and holds important advantages over probucol in that it has fewer adverse effects on high-density lipoprotein cholesterol and the QT interval.

Conclusions: The favorable safety profile of AGI-1067 offers potential advantages over its precursor, probucol. Preclinical and clinical studies indicate that it possesses antioxidant, antiinflammatory, and lipid-lowering properties. Ongoing Phase II and III studies will determine AGI-1067's place in therapy for the prevention of restenosis and reduction in cardiovascular events in patients undergoing percutaneous intervention for coronary atherosclerosis.