Effect of statins on HDL-C: a complex process unrelated to changes in LDL-C: analysis of the VOYAGER Database

Abstract

The relationship between statin-induced increases in HDL cholesterol (HDL-C) concentration and statin-induced decreases in LDL cholesterol (LDL-C) is unknown. The effects of different statins on HDL-C levels, relationships between changes in HDL-C and changes in LDL-C, and predictors of statin-induced increases in HDL-C have been investigated in an individual patient meta-analysis of 32,258 dyslipidemic patients included in 37 randomized studies using rosuvastatin, atorvastatin, and simvastatin. The HDL-C raising ability of rosuvastatin, and simvastatin was comparable, with both being superior to atorvastatin. Increases in HDL-C were positively related to statin dose with rosuvastatin and simvastatin but inversely related to dose with atorvastatin. There was no apparent relationship between reduction in LDL-C and increase in HDL-C, whether analyzed overall for all statins (correlation coefficient = 0.005) or for each statin individually. Percentage increase in apolipoprotein A-I was virtually identical to that of HDL-C at all doses of the three statins. Baseline concentrations of HDL-C and triglyceride (TG) and presence of diabetes were strong, independent predictors of statin-induced elevations of HDL-C. Statins vary in their HDL-C raising ability. The HDL-C increase achieved by all three statins was independent of LDL-C decrease. However, baseline HDL-C and TGs and the presence of diabetes were predictors of statin-induced increases in HDL-C.

Fig. 1.

Relationship between changes in concentrations of HDL-C and apoA-I during treatment with atorvastatin at 10, 20, 40, or 80 mg/day, rosuvastatin at 5, 10, 20, or 40 mg/day, or simvastatin at 10, 20, 40, or 80 mg/day. The diagonal lines depict a 1:1 relationship.

Fig. 2.

Relationship between changes in concentrations of HDL-C and LDL-C. Individual data for all patients (38,199 patient exposures) receiving any dose of rosuvastatin, atorvastatin, or simvastatin are shown (r = 0.02).

Fig. 3.

Impact of baseline concentrations of HDL-C, plasma TG, and LDL-C and patient characteristics on changes in HDL-C during treatment with rosuvastatin at either 10 mg or 40 mg. Results are means (95% CI). BMI, body mass index; Q, quintile (see text for definition).

Fig. 4.

Impact of baseline concentrations of HDL-C, plasma TG, and LDL-C and patient characteristics on changes in HDL-C during treatment with atorvastatin at either 20 mg or 80 mg. Results are means (95% CI). BMI, body mass index; Q, quintile (see text for definition).