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Clin Ther. 2014 Aug 1;36(8):1182-90. doi: 10.1016/j.clinthera.2014.06.005. Epub 2014 Jul 2.

Comparison of the efficacy and safety profile of morning administration of controlled-release simvastatin versus evening administration of immediate-release simvastatin in chronic kidney disease patients with dyslipidemia.

Author information

1
Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea.
2
Department of Internal Medicine, Korea University Medical College, Seoul, Republic of Korea.
3
Division of Nephrology, Department of Internal Medicine, Hallym University Sacred Heart Hospital, Anyang, Republic of Korea.
4
Department of Internal Medicine, Gachon University of Medicine and Science, Incheon, Republic of Korea.
5
Department of Internal Medicine, Inje University Ilsan Paik Hospital, Ilsan, Republic of Korea.
6
Department of Internal Medicine, Hanyang University, Seoul, Republic of Korea.
7
Department of Internal Medicine, Eulji General Hospital, Eulji University, Seoul, Republic of Korea.
8
Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea. Electronic address: khoh@snu.ac.kr.

Abstract

PURPOSE:

Evening administration of the conventional immediate-release (IR) formulation of simvastatin is recommended because of its short half-life (1.9 hours). In a healthy population, morning administration of a controlled-release (CR) formulation of simvastatin was shown to have equivalent lipid-lowering efficacy and a safety profile similar to that of evening doses of IR simvastatin. The present study aimed to verify noninferiority and to compare the safety of morning administration of CR simvastatin with that of evening administration of IR simvastatin in patients with chronic kidney disease (CKD) who have dyslipidemia.

METHODS:

The present study was a prospective, multicenter, double-blind, Phase IV trial with an active comparator. We randomly assigned 122 patients with CKD and dyslipidemia to 1 of 2 drug administration groups: morning administration of CR simvastatin 20 mg (test group) and evening administration of IR simvastatin 20 mg (control group). After 8 weeks, the treatment outcomes and adverse effects of the 2 treatments were compared.

FINDINGS:

The mean (SD) percentage of change in serum LDL-C at the end of treatment was -35.1% (15.7%) for the test group and -35.6% (14.6%) for the control group. The difference between the 2 groups was not significant (P = 0.858). The 95% CI of the difference in the percentage of change of LDL-C between the test and control groups was -6.0 to 5.0. There was no difference in the percentage of change of total cholesterol (-24.3% [12.5%] vs -26.5% [12.0%], P = 0.317), triglyceride (-10.6% [35.1%] vs -12.4% [33.2%], P = 0.575) and HDL-C (10.2% [20.7%] vs 4.5% [11.4%], P = 0.064). Treatment-related adverse events were similar in both groups (10 events in the test group vs 8 events in the control group, P = 0.691).

IMPLICATIONS:

The efficacy of morning administration of CR simvastatin was noninferior to evening administration of IR simvastatin in patients with CKD. Furthermore, the safety profile analysis showed no significant difference between the 2 treatments. Morning administration of CR simvastatin is expected to increase patient compliance and therefore better control of dyslipidemia in CKD patients.

KEYWORDS:

chronic kidney disease; controlled-release preparations; drug administration schedule; dyslipidemia, simvastatin

PMID:
24996489
DOI:
10.1016/j.clinthera.2014.06.005
[Indexed for MEDLINE]
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