Antioxidants: the good, the bad and the ugly.

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.