Effect of simvastatin on Lp(a) concentrations

The effect of HMG-CoA reductase inhibitors on Lp(a) concentrations is controversial, with some studies showing an increase and others showing no effect on Lp(a) concentrations. Many of these studies have been limited by small sample size and the lack of a prospective design. We evaluated the effect of four treatments: (1) placebo, (2) simvastatin 10 mg PO QPM, (3) simvastatin 20 mg PO QAM, and (4) simvastatin 20 mg PO QPM on Lp(a) concentrations in a prospective, randomized, controlled clinical trial of 24 weeks in 343 subjects in 28 clinical sites in the United States. Simvastatin was not associated with a change in Lp(a) concentrations relative to placebo. These results were not affected by controlling for race, initial Lp(a) level, or urinary albumin excretion. Simvastatin significantly reduced low-density lipoprotein (LDL) cholesterol levels (10 mg PO QPM: -27.6%; 20 mg PO QAM: -28.1%; and 20 mg PO QPM: -34.3%, all p < 0.001). It was concluded that in a large, randomized, controlled trial, simvastatin does not affect Lp(a) levels but markedly lowers LDL cholesterol levels.