Statins and total (not LDL) cholesterol concentration and outcome of myocardial infarction: results from a meta-analysis and an observational study

The purpose of this study was to evaluate how total cholesterol (TC) concentration in subjects treated with statins predicts myocardial infarction (MI) risk in the absence of low density lipoprotein cholesterol (LDL-C) measurement in clinical trials and in the setting of usual care.

A systematic review of published English language randomised clinical trials comparing statins with placebo that reported TC changes in subjects with or without prior MI between 1993 and 2008 was carried out using Medline, the Cochrane Library, Web of Science and the ISI Web of Knowledge. In addition, a cohort study of MI patients who had at least two TC measurements in Tayside, Scotland, between 1989 and 2002 was performed. The main outcome was TC concentration changes and risk of subsequent MI.

In the meta-analyses of secondary and primary prevention trials statins decreased TC by 1.54 mmol/L and 1.37 mmol/L versus placebo. Statin-associated TC reduction translated into a risk reduction of 18% per mmol (RR 0.82; 95%CI 0.72-0.93) for secondary prevention and 24% per mmol (RR 0.76; 95%CI 0.62-0.93) for primary prevention. In the cohort study, statin use reduced TC by 0.98 mmol/L compared with non statin-use. Statin use was associated with a 28% reduction (adjusted HR 0.72; 95%CI 0.51-0.98) for recurrent MI.

Total cholesterol measurements can be used with confidence in the absence of LDL measurements to make decisions about statin drug introduction or titration. Randomised trials of statin therapy had good external validity and cholesterol changes and outcomes in trials were comparable to those observed in the setting of usual care.