Published in:
01-12-2013 | Original Research Article
Short-Term Impact of Low-Dose Atorvastatin on Serum Proprotein Convertase Subtilisin/Kexin Type 9
Published in: Clinical Drug Investigation | Issue 12/2013
Login to get accessAbstract
Background and Objective
Several small studies have found that moderate- to high-dose statins (HMG-CoA reductase inhibitors) could increase the serum proprotein convertase subtilisin/kexin type 9 (PCSK9) level. However, little is known regarding the short-term, dose-dependent effects of low-dose atorvastatin and the rapid effects of a single dose of atorvastatin on PCSK9. The objective of this study was to investigate the short-term impact of low-dose atorvastatin on PCSK9 in humans.
Methods
In this randomized study, data from 66 subjects were analyzed. In protocol I, 32 patients were randomized to atorvastatin 10 mg/day (n = 19) or 20 mg/day (n = 13) and eight healthy subjects without therapy were controls for 8 weeks. Serum PCSK9 and lipid profile were determined at day 0, week 4, and week 8. In protocol II, 26 patients were randomized to a single dose of atorvastatin 10 mg (n = 11) or 80 mg (n = 15), and serum levels of PCSK9 were measured at 24 h after treatment.
Results
Atorvastatin 10 mg/day decreased low-density lipoprotein cholesterol (LDL-C) by 32 % at 4 weeks and by 33 % at 8 weeks, and atorvastatin 20 mg/day resulted in reduction of LDL-C by 41 % at 4 weeks and by 38 % at 8 weeks. Atorvastatin 10 mg/day slightly increased serum PCSK9 by 5–7 % but without a significant difference, while atorvastatin 20 mg/day significantly increased serum PCSK9 by 30 % at 4 weeks and by 35 % at 8 weeks (p = 0.009 and p = 0.002, respectively). In addition, 24 h after a single dose, atorvastatin 10 mg significantly increased serum PCSK9 by 13 % and atorvastatin 80 mg by 27 % (p = 0.042 and p = 0.001, respectively).
Conclusion
The short-term impact of low-dose atorvastatin on PCSK9 was time and dose dependent, with a rapid increase in PCSK9 levels being observed within 24 h of dosing.