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

Yong Jin Yi, Hyo Jin Kim, Sang Kyung Jo, Sung Gyun Kim, Young Rim Song, Wookyung Chung, Kum Hyun Han, Chang Hwa Lee, Young Hwan Hwang, Kook Hwan Oh

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)1182-1190
Number of pages9
JournalClinical Therapeutics
Volume36
Issue number8
DOIs
Publication statusPublished - 2014 Aug 1

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Simvastatin
Dyslipidemias
Chronic Renal Insufficiency
Safety
Control Groups
Therapeutics
Patient Compliance
Half-Life
Triglycerides
Cholesterol
Lipids

Keywords

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

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Cite this

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. / Yi, Yong Jin; Kim, Hyo Jin; Jo, Sang Kyung; Kim, Sung Gyun; Song, Young Rim; Chung, Wookyung; Han, Kum Hyun; Lee, Chang Hwa; Hwang, Young Hwan; Oh, Kook Hwan.

In: Clinical Therapeutics, Vol. 36, No. 8, 01.08.2014, p. 1182-1190.

Research output: Contribution to journalArticle

Yi, Yong Jin ; Kim, Hyo Jin ; Jo, Sang Kyung ; Kim, Sung Gyun ; Song, Young Rim ; Chung, Wookyung ; Han, Kum Hyun ; Lee, Chang Hwa ; Hwang, Young Hwan ; Oh, Kook Hwan. / 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. In: Clinical Therapeutics. 2014 ; Vol. 36, No. 8. pp. 1182-1190.
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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.",
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AU - Kim, Hyo Jin

AU - Jo, Sang Kyung

AU - Kim, Sung Gyun

AU - Song, Young Rim

AU - Chung, Wookyung

AU - Han, Kum Hyun

AU - Lee, Chang Hwa

AU - Hwang, Young Hwan

AU - Oh, Kook Hwan

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N2 - 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.

AB - 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.

KW - chronic kidney disease

KW - controlled-release preparations

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KW - dyslipidemia, simvastatin

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