High-dose statin therapy with rosuvastatin reduces small dense LDL and MDA-LDL: The Standard versus high-dose therApy with Rosuvastatin for lipiD lowering (SARD) trial.

BACKGROUND

Cardiovascular events (CV) continue to occur due to residual risks in high-risk patients in spite of substantial reductions in the low-density lipoprotein cholesterol (LDL) with statins. It has been reported that the small-dense LDL (sd-LDL) components of high atherogenic particles are associated with an increased risk of CV, more than large buoyant LDL. However, there are few reports regarding the effects of high-dose statin therapy in improving atherogenic lipoproteins.

METHODS AND RESULTS

In this prospective, randomized, open-label, multicenter study, a total of 111 high-risk patients were randomly assigned to two groups. In the high-dose therapy group, 58 patients were administered 5mg of rosuvastatin per day for four weeks, after which the dose was titrated to 10mg for the following eight weeks. In the low-dose therapy group, 53 patients were given 2.5mg for 12 weeks. We evaluated the lipid profiles, including the levels of sd-LDL, malondialdehyde-modified LDL-cholesterol (C) (MDA-LDL) as oxidized-LDL, and remnant-like particle-cholesterol. The LDL-C, non-high-density lipoprotein (HDL), and LDL-C/HDL-C ratio were decreased in the high-dose therapy group (p<0.01). Moreover, the sd-LDL and MDA-LDL levels were significantly reduced in the high-dose therapy group (p<0.05). There were no serious adverse events in either group.

CONCLUSIONS

High-dose statin therapy significantly reduced the sd-LDL and MDA-LDL components of atherosclerotic lipoproteins without adverse events in comparison with low-dose statin therapy.