Comparison of the impact of atorvastatin and simvastatin on apoA-I kinetics in men

Background: The impact of simvastatin and atorvastatin, two HMG-CoA inhibitors, on plasma HDL-C concentrations has been shown to be inconsistent, simvastatin being reported to induce greater increases in HDL-C than atorvastatin. The physiological mechanisms underlying this diverging effect are still unknown. Objectives: To compare the impact of simvastatin and atorvastatin on apoA-I kinetics in vivo. Methods: In this double-blind, cross-over study, seven men with relatively low baseline HDL-C were assigned in random order to one of two experimental 8-week treatments (atorvastatin 40 mg or simvastatin 80 mg), each separated by a 6-week washout period. After each phase, apoA-I kinetics were measured using a primed-constant infusion of l-(5,5,5-D3) leucine for 12 h with patients being kept in constant fed, steady state. Isotopic enrichment of apoA-I over time was assessed by gas chromatography–mass spectrometry and kinetic parameters were calculated by multicompartmental modeling. Results: Both treatments reduced plasma LDL-C levels to a similar extent while HDL-C levels remained statistically unchanged after both experimental phases. However, compared to atorvastatin, plasma apoA-I concentrations were significantly higher after treatment with simvastatin (1.33 ± 0.07 g/L versus 1.23 ± 0.07 g/L, P = 0.05). Treatment with simvastatin also induced a significant increase in apoA-I production rate compared to atorvastatin (15.2 ± 3.0 mg/kg/d versus 13.2 ± 2.6 mg/kg/d, P = 0.05). There was no statistical difference in apoA-1 fractional catabolic rate between simvastatin and atorvastatin (0.26 ± 0.05 pool/d versus 0.24 ± 0.04 pool/d). Conclusions: These results suggest that the diverging impact of simvastatin and atorvastatin on plasma HDL-C levels in humans may be attributable, at least partly, to a greater production rate of apoA-I with simvastatin.