Trial DesignStudy of the effectiveness of additional reductions in cholesterol and homocysteine (SEARCH): Characteristics of a randomized trial among 12 064 myocardial infarction survivors☆,☆☆
Section snippets
More intensive cholesterol lowering:balance of benefits versus risks
There is a general agreement that blood cholesterol is an important cause of coronary heart disease (CHD). Observational studies indicate a continuous positive relationship between CHD risk and blood low-density lipoprotein cholesterol (LDL-C) level that extends well below the range currently seen in western populations, without any definite threshold below which a lower level is not associated with lower risk.1, 2 In the past decade, several large randomized trials of statin therapy have
Aims
SEARCH aims to demonstrate reliably whether a more intensive cholesterol-lowering regimen using simvastatin 80 mg daily safely produces a greater reduction in cardiovascular risk than does a standard simvastatin 20 mg daily regimen. In addition, SEARCH aims to obtain reliable evidence about the effects on cardiovascular risk of homocysteine-lowering with folic acid 2 mg plus vitamin B12 1 mg daily. 12 064 MI survivors aged between 18 and 80 years have been randomized to receive intensive versus
Identification and invitation of potentially eligible people to screening clinics
Medical collaborators from 88 UK hospitals supervised senior nurses who ran the local study clinics. Relevant ethics committee and regulatory agency approvals were obtained. Records of patient hospital discharges after MI were used to identify potentially eligible candidates. In accordance with the Data Protection Act, the coordinating center staff in the Clinical Trial Service Unit, University of Oxford, Oxford, UK, processed these data in confidence on behalf of the local hospitals. Having
Need for reliable assessment of benefits versus risks of intensive lipid lowering
Statin therapy is now widely recommended for both primary and secondary prevention of vascular disease in high-risk groups.22, 23 However, there is uncertainty about the value of more intensive cholesterol-lowering therapy. Most current guidelines recommend targets for treatment, typically aiming for LDL-C <2 mmol/L.22 Evidence from observational studies and from randomized trials is generally consistent with lower LDL-C levels being associated with lower risks of vascular disease.1, 3 Four
Conclusion
SEARCH has randomized 12 064 heart attack survivors and currently has median follow-up of more than 6 years. During 2008, it should provide a reliable and relevant assessment of whether lowering LDL-C more with intensive simvastatin therapy safely produces further benefits. By also randomizing these patients to B-vitamin therapy or placebo, SEARCH will also generate uniquely reliable evidence about the causal nature of the association between blood homocysteine and cardiovascular disease, and
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Cited by (0)
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The study is funded by a grant to the University of Oxford, Oxford, United Kingdom, from Merck & Co, Inc, Whitehouse Station, NJ. It has, however, been designed and conducted, and will be analyzed and interpreted by the Clinical Trial Service Unit independently of this source of support.
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The Clinical Trial Service Unit has a staff policy of not accepting honoraria or other payments from the pharmaceutical industry, except for reimbursement of costs to participate in scientific meetings.
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Collaborators and participating hospitals are listed in Web-Appendix 4