Inflammation has a fundamental role in mediating all stages of atherosclerotic disease. The key role of oxidation in linking
lipids and
inflammation to
atherosclerosis is compelling and supported by experimental evidence. However, the relevance of the
antioxidant hypothesis for the treatment of patients with
atherosclerosis has not been definitively proven.
Probucol has reduced post-
percutaneous coronary intervention (PCI) restenosis and progression of
carotid atherosclerosis in clinical trials. The
antioxidant/vascular protectant
AGI-1067 has also been effective at preventing
atherosclerosis in all tested animal models. The nonintervened reference coronary segments of the PCI vessel demonstrated improvements with
AGI-1067 in the Canadian
Antioxidant Restenosis Trial-1 (CART-1), evidence supportive of a clinical effect on slowing
atherosclerosis progression. Results of randomized trials with the "
antioxidant"
vitamins have been disappointing, but there are potentially important problems associated with their use, including their potential
pro-oxidant effects. Two important trials that test the
antioxidant/anti-inflammatory hypothesis are ongoing with
AGI-1067: CART-2, which assesses its value for the reduction of both
atherosclerosis progression in non-PCI vessels and post-PCI restenosis; and Aggressive Reduction of
Inflammation Stops Events (ARISE), which is evaluating the effects of
AGI-1067 on hard cardiovascular outcomes.