Eighteen RCTs were included, one of which was unpublished.
Only 2 studies scored the maximum 4 points for quality; 4 studies scored 3 points and 12 scored 2 points. Compliance was not reported in most studies, but when reported was high (>80% to >90%). Crossovers between treatment arms were not reported. The rates of follow-up were over 85% in all trial arms except two (which had follow-up rates of 79% and 83%).
Change in TC (16 comparisons): the relative reductions in TC were comparable when simvastatin doses were two to four times higher than atorvastatin. Atorvastatin was associated with significantly greater reductions in TC than simvastatin in 13 of 16 dose-pair comparisons (p<0.001). A single comparison (simvastatin 80 mg versus atorvastatin 10 mg) significantly favoured simvastatin (p<0.001).
Change in LDL-C (16 comparisons): the relative reductions in LDL-C were comparable when simvastatin doses were two to four times higher than atorvastatin. Atorvastatin was associated with significantly greater reductions in LDL-C than simvastatin in 13 of 16 dose-pair comparisons (p<0.001). Three comparisons significantly favoured simvastatin: simvastatin 40 mg and 80 mg versus atorvastatin 10 mg (p=0.01 and p<0.001, respectively) and simvastatin 80 mg versus atorvastatin 20 mg (p<0.001).
Change in TG (16 comparisons): the relative reductions in TG were comparable when simvastatin doses were twice atorvastatin doses. Atorvastatin was associated with significantly greater reductions in TG than simvastatin in 12 of 16 dose-pair comparisons. Neither treatment was statistically superior for 4 dose comparisons: simvastatin 40 mg and 80 mg versus atorvastatin 10 mg, and simvastatin 40 mg and 80 mg versus atorvastatin 20 mg.
Change in HDL-C (16 comparisons): simvastatin was associated with significantly greater increases in HDL-C than atorvastatin in 7 of 16 dose-pair comparisons (p-values ranged from p=0.03 to p<0.001). There was no indication of dose-equivalence: the benefits of simvastatin appeared highest when atorvastatin was at its highest daily dose.
No statistically significant heterogeneity was evident for any of the comparisons, although there were marked differences between the trials (e.g. with respect to participant characteristics and trial duration).
Twelve RCTs addressed safety. Drug tolerance and the incidence of adverse events were similar in the two treatment groups (data not reported). The most common adverse events were gastrointestinal complaints and myalgia.