Optimal low-density lipoprotein cholesterol lowering - Morning versus evening statin administration

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.