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 is supported by experimental evidence. However, the relevance of the
antioxidant hypothesis for the treatment of patients with
atherosclerosis has not been definitively proven. Results of randomized trials with '
antioxidant'
vitamins have been disappointing, and there are potentially important problems associated with their use, including their potential
pro-oxidant effects.
Probucol has reduced postpercutaneous 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. Two trials test the
antioxidant/anti-inflammatory hypothesis with
AGI-1067; CART-2 assesses its value for the reduction of both
atherosclerosis progression and post-PCI restenosis, and Aggressive Reduction of
Inflammation Stops Events (ARISE), which is evaluating its effects on hard cardiovascular outcomes.