text: OBJECTIVE: The aim of this review is to objectively access the trial evidence on the role of omega-3, red yeast rice and garlic in preventing clinical cardiovascular events. Given the large number of clinical trials favoring statin use in cardiovascular disease, it is important to see if evidence is available for these supplements and whether they could replace statin therapy. DATA SOURCE: A PubMed search was conducted using the keywords 'trial, omega-3, red yeast rice, xuezhikang, garlic, cholesterol, cardiovascular, outcomes'; the resulting trials were reviewed together with the references quoted in the papers obtained. STUDY SELECTION: The studies selected are prospective, randomized, placebo-controlled studies with predefined clinical cardiovascular end-points recruiting at least 2000 patients, with a follow-up over 2 years. RESULTS: Modest dose omega-3 fatty acid has been shown in GISSI-P (11 324 patients, follow-up 3.5 years) to produce a reduction in sudden death of 45%, and in cardiac death of 35%, acting probably via an anti-arrhythmic effect. In JELIS (18 645 patients, follow-up 4.6 years), high dose omega-3 given to Japanese patients on a high fish diet and already on statin treatment produced further benefit with a 19% reduction of nonfatal cardiovascular outcomes; fatal cardiac events are not affected. CCSPS (4870 patients, follow-up 4 years), a secondary prevention trial using xuezhikang, a commercial red yeast rice preparation, produced a 46% reduction in nonfatal myocardial infarction and coronary death. There has been no trial to show that garlic reduces clinical cardiovascular outcomes. A rigorous trial with constant assessment of chemicals in the study material in 192 patients found that over a 6-month follow-up, raw garlic and 2 commercial preparations do not significantly affect lipid levels. CONCLUSIONS: Omega-3 in modest doses reduces cardiac deaths, and in high doses reduces nonfatal cardiovascular events. Red yeast rice reduces adverse cardiac events to a similar degree as the statins. It is unlikely that garlic is useful in preventing cardiovascular disease.