COMMENTARY

Statins: Morning vs Evening Dosing?

Jacqueline H. Kostick, PharmD

Disclosures

March 12, 2007

Optimal Low-Density Lipoprotein Cholesterol Lowering -- Morning Versus Evening Statin Administration

This viewpoint offers commentary on important clinical research in the area of pharmacy.

Plakogiannis R, Cohen H
Ann Pharmacother. 2007;41:106-110

Study Summary

This literature review investigated the chronobiologic effects of morning vs evening administration of statins on low-density lipoprotein cholesterol (LDL-C). Based on the 7 clinical trials reviewed, simvastatin demonstrated a significant low-density lipoprotein cholesterol (LDL-C) percentage reduction when administered in the evening, compared with morning administration. Although not significantly significant, the authors also noted a trend favoring evening statin administration with lovastatin, pravastatin, and rosuvastatin. Atorvastatin appears to decrease LDL-C regardless of the time administered. The authors were not able to identify any clinical studies involving the optimum time for administering fluvastatin.

Viewpoint

The National Cholesterol Education Program Adult Treatment Panel III advocates statins as first-line therapy for lowering LDL-C levels.[1] Given that cholesterol is biosynthesized in the early morning hours,[2] the US Food and Drug Administration (FDA) has recommended evening administration for statins with shorter half-lives (lovastatin 2 hours, simvastatin < 5 hours, and fluvastatin < 3 hours). In contrast, the FDA suggests daytime administration for statins with longer half-lives (atorvastatin 14 hours, rosuvastatin 19 hours, and pravastatin 22 hours). Atorvastatin also has active metabolites with half-lives ranging from 20 to 30 hours, which may contribute to the fact that it can be taken at any time.

In this literature review, the only statistically significant conclusion was that simvastatin should be taken in the evening to optimize the reduction of LDL-C levels. Most of the chronobiologic studies included in this review failed to provide statistically significant data, they lacked large sample sizes, and in some cases, they did not provide P values or exclusion criteria. Future prospective, randomized trials with larger samples of hyperlipidemic patients are necessary to form clear conclusions as to the ideal statin administration time. In the meantime, the authors concluded that the available evidence supports evening administration of lovastatin and fluvastatin (as well as simvastatin), and daytime administration of pravastatin, rosuvastatin, and atorvastatin, for maximal LDL-C lowering.

Abstract

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