Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine (SEARCH)
12,064 randomised
Recent intervention studies have demonstrated worthwhile benefits with statin cholesterol-lowering therapy in some types of very high-risk patients, but such patients are still at elevated risk of CHD with the regimens studied [39]. Epidemiological studies of blood homocysteine provide reasonably consistent evidence of a positive association with the risk of occlusive vascular disease [40], but there is very little randomised controlled evidence about the effects on risk of lowering blood homocysteine levels.
The SEARCH randomised trial aims to demonstrate reliably whether a larger reduction in cholesterol, with a regimen of 80 mg daily simvastatin, produces worthwhile further reductions in CHD compared with a standard 20 mg daily regimen. In addition, using a factorial design, the effects of lowering homocysteine with folic acid will be assessed [41,42]. Reductions in CHD of 15-20% are plausible, and to be able to detect such effects about 12,000 MI survivors from 90 UK hospitals are to be studied for 5 years (results in 2007/8).
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