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DRUG INFORMATION ROUNDS

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

Assistant Professor of Pharmacy Practice, Arnold & Marie Schwartz College of Pharmacy and Health Sciences, Long Island University, Brooklyn, NY; Clinical Pharmacy Specialist—Primary Care, Bellevue Hospital Center, New York, NY

Henry Cohen, MS PharmD FCCP BCPP CGP

Associate Professor of Pharmacy Practice, Arnold & Marie Schwartz College of Pharmacy and Health Sciences, Long Island University; Director of Pharmacotherapy Research, Education, and Residency Programs, Department of Pharmacy, Kingsbrook Jewish Medical Center, Brooklyn, NY

Reprints: Dr. Plakogiannis, Arnold & Marie Schwartz College of Pharmacy and Health Sciences, Long Island University, 75 DeKalb Ave., Brooklyn, NY 11201, roda.plakogiannis{at}liu.edu

OBJECTIVE: To determine the best time to administer statins for optimal lowering of low-density lipoprotein cholesterol (LDL-C) by reviewing the clinical evidence evaluating the chronobiologic effects of morning versus evening statin administration.

DATA SOURCES: Using the MeSH terms HMG-CoA reductase inhibitors, statins, morning and evening dosing, and clinical trials, a literature review was conducted to identify articles in MEDLINE (1966–December 2006), International Pharmaceutical Abstracts (1970–December 2006), and IOWA Drug Information Systems (1985–December 2006).

DATA SYNTHESIS: Seven English-language studies evaluating morning and evening statin administration were identified and evaluated. Based on the available data, simvastatin demonstrated a pronounced LDL-C percentage reduction with evening dosing. Although not statistically significant, a trend in the LDL-C percentage reduction favoring evening statin administration was noted with lovastatin, pravastatin, and rosuvastatin. Atorvastatin demonstrated similar LDL-C reduction regardless of administration time. With the exception of simvastatin, the trials comparing morning versus evening effects of statins on LDL-C have several significant methodologic shortcomings, including small sample size, lack of statistical power, and inappropriate exclusion criteria that did not include or did not mention drug-induced effects on lipids.

CONCLUSIONS: There are sufficient data to support evening administration of simvastatin to achieve optimal lowering of LDL-C levels. Rigorous and robust trials are necessary to determine the best administration time to achieve optimal LDL-C lowering for lovastatin, pravastatin, rosuvastatin, atorvastatin, and fluvastatin.

Key Words: atorvastatin, dosing, fluvastatin, lovastatin, pravastatin, rosuvastatin, simvastatin

Published Online, January 2, 2007. www.theannals.com, DOI 10.1345/aph.1G659

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