Statin alternatives or just placebo: an objective review of omega-3, red yeast rice and garlic in cardiovascular therapeutics.

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. Chin Med J 2008;121(16):1588-1594 espite the overwhelming evidence favoring prescription drug therapy, the public is keen on herbal and dietary medicine, sales of which in the United States are estimated at $4 billion annually. 1 A telephone survey in 2002 revealed that 18.8% of 8470 subjects had used herbal or other natural products in the preceding week. 2 Over 20% of adults on prescription medication also use dietary supplements, although most do not report this to their doctors. 3 It is thus important that medical doctors objectively analyze the evidence on herbal and dietary medicine so that they can confidently guide patients in its usage. The evidence favoring statin therapy in preventing cardiovascular events is highly convincing, with over 200 000 patients randomized in prospective randomized controlled trials around the world. 4,5 To objectively assess the role of dietary products in cardiovascular disease, it is important to seek out similar prospective, randomized, long term trials with clinical end-points. Omega-3 fatty acids (eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA)), red yeast rice (RYR) and garlic are chosen for this review since they are commercially available as oral supplements and have been promoted for their cardiovascular protective effects. A three step PubMed search was conducted using the