NPC Archive Item: Is lower cholesterol better? – the SEARCH continues

NOTE – This is an archive post from the NPC and has not been updated since first publication. Therefore, some hyperlinks may no longer be working.
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Early results of the SEARCH study have been presented at the American Heart Association conference and as such have not yet been fully evaluated. They suggest no statistically significant benefit on cardiovascular events from simvastatin 80mg versus 20mg in patients with a history of an MI.  However, there was an increased risk of myopathy with the higher dose.

Clinicians should follow NICE guidance on lipid management and use simvastatin 40mg for primary and secondary prevention. In secondary prevention, increasing the dose to 80mg in certain circumstance may be considered, but the absolute benefit that an individual patient could expect to achieve from additional cholesterol lowering should be balanced against the increased risk of side effects.

The Clinical Trial Service Unit at the University of Oxford has announced the summary results of the SEARCH study at the American Heart Association conference: the press release is available here and the slides used at the conference are available here. It is important to view these preliminary results with caution as the study has not yet been published and therefore a full critical appraisal of the data has not been possible.

The study aimed to assess the impact of intensive lipid lowering with simvastatin 80mg versus standard therapy with simvastatin 20mg in 12,064 participants who had had a heart attack.  It also compared folic acid and vitamin B12 supplementation with placebo.

The study ran for a mean of 6.7 years. Intensive treatment lowered  LDL-cholesterol by an average of 0.35mmol/L compared with standard treatment. This reduction was associated with an observed 6% relative reduction in risk of heart attacks, stroke and revascularisation procedures, which was not statistically significant. There was also no significant effect on vascular mortality or all-cause mortality.  In addition, the study also found that there was no benefit from folic acid and vitamin B12 supplementation in the secondary prevention of vascular events.

It is also notable that 3 patients (0.05%) treated with simvastatin 20mg developed myopathy compared to 53 (0.88%) taking simvastatin 80mg. This is a relative risk increase of 1667% and a number needed to harm (NNH) of 121. Seven people in the simvastatin 80mg group developed rhabdomyolosis but none of the people in the simvastatin 20mg group developed this.

The press release states that the study results, although not statistically significant, are consistent with data from a meta-analysis showing that a 0.35mmol/L reduction in LDL-cholesterol is associated with a relative risk reduction of 6 to 7% and, therefore, supports the assertion that lower LDL-cholesterol is better.  However, it is important to note that this is a relative risk reduction.  Absolute data are not provided in the press release or slides, and the difference observed in SEARCH was not statistically significant.  However, if it really exists, an extra 6% relative risk reduction is approximately equivalent to an additional 3 events prevented over 10 years in 100 people with a 50% 10-year risk of major cardiovascular events, or 1 additional event prevented over 10 years in 100 people with a 20% 10-year risk of major cardiovascular events.

This blog is based on one posted on Matt Robinson’s Prescribing advice for GPs site, and used with kind permission.

More information on lipid management can be found on the lipids section of NPC.

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