At the same late breaking clinical trials session, Armitage's co-principal investigator, Professor Rory Collins, professor of medicine and epidemiology at the University of Oxford, presented a second randomized comparison from the SEARCH trial of 80mg versus 20mg per day of simvastatin -- the largest direct comparison of more versus less intensive lowering of low-density lipoprotein cholesterol (LDL-C).
Previous studies have found that statin therapy reduces the relative risk of MVE by about 20 percent per 40 milligram per deciliter (mg/dL) reduction in LDL-C. Compared with the patients assigned 20mg per day of simvastatin in SEARCH, LDL-C was reduced by an average of 14mg/dL more among the patients assigned 80mg per day of simvastatin.
Collins presented the results of SEARCH in the context of an update of a meta-analysis of individual patient data from previous studies of statin therapy published in The Lancet in 2005 (Lancet 2005 Oct 8: 366:1267-78.) Based on that meta-analysis, a 14 mg/dL greater reduction in LDL-C would be expected to produce a 6 percent to 7 percent relative reduction in MVE, which is what researchers observed in the SEARCH trial.
Daily doses of 80mg simvastatin were associated with more myopathy cases than 20mg simvastatin, although the SEARCH trial had identified a genetic variant that accounted for much of the excess myopathy risk with the higher-dose simvastatin regimen.
Co-authors are the SEARCH Collaborative Group. Individual author disclosures are available on the abstract.
The University of Oxford's Clinical Trial Service Unit designed, conducted, analyzed and interpreted the SEARCH study, which was funded by a research grant from Merck & Co.
Statements and conclusions of study authors that are presented a
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