Statin treatment - morning versus nighttime (night) dose

• the rate of cholesterol synthesis in the liver shows diurnal periodicity, with production peaking at nighttime
  • statins act by inhibiting the enzyme HMG CoA reductase, which controls synthesis of cholesterol in the liver. Most manufacturers of statins recommend that they are taken at night, on the basis of physiological studies which show that most cholesterol is synthesised when dietary intake is at its lowest (1)
• Timing of dosing of simvastatin - nighttime or morning?
  • a small study by Lund et al (2) found significant differences in total cholesterol and LDL when comparing simvastatin use in the morning and at nighttime
    • Lund et al have shown that simvastatin, which has a short elimination half-life, taken in the evening instead of the morning decreases the total cholesterol and LDL cholesterol levels more significantly and that alternating times of simvastatin ingestion does not change HDL cholesterol or triglyceride levels
    • found a 7.3% higher total cholesterol and a 13.4% increase in LDL when the ingestion time was in the morning compared to the patient previously taking medication at nighttime
  • a systematic review has also concluded that the evidence base supports evening administation of simvastatin (3)
• Timing of dosing of other statins
  • a systematic review revealed a statistically nonsignificant trend in the LDL-C percentage reduction favouring evening statin administration with lovastatin, pravastatin, and rosuvastatin (3)
    • atorvastatin (a longer elimination half-life than simvastatin) demonstrated similar LDL-C reduction regardless of administration time
    • the study authors concluded that there are sufficient data to support evening administration of simvastatin to achieve optimal lowering of LDL-C levels
    • there is however insufficient evidence to support nightime or evening administration of the other statins included in the review
  • a fluvastatin study revealed that the efficacy and safety profiles of fluvastatin XL are equivalent for morning and evening administration

Notes:

• the elimination half-lives of atorvastatin, pravastatin and rosuvastatin are significantly longer than that of simvastatin and this is probably significant in the ability to take these other statins in the morning with non-significant changes in lipid lowering compared to evening administration:
  • half-lives
    • simvastatin < 5 hours
    • atorvastatin 14 hours
    • rosuvastatin 19 hours
    • and pravastatin 22 hours
  • atorvastatin also has active metabolites with half-lives ranging from 20 to 30 hours
  • this data therefore supports the night-time dosing of simvastatin but there is insufficient evidence to recommend only night-time dosing of statins other than simvastatin

Reference:

• 1. Jones PJH, Schoeller DA. Evidence ofor diurnal periodicity in human cholesterol synthesis. J Lipid Res 1990;31:667-673
• 2. Lund TM et al. .Effect of morning versus evening intake of simvastatin on the serum cholesterol level in patients with coronary artery disease. The American Journal of Cardiology 2002;90 (7): 784-786.
• 3. Plakogiannis R et al. Optimal low-density lipoprotein cholesterol lowering--morning versus evening statin administration. Ann Pharmacother. 2007 Jan;41(1):106-10.
• 4. Scharnagl H et al. Efficacy and safety of fluvastatin-extended release in hypercholesterolemic patients: morning administration is equivalent to evening administration. Cardiology. 2006;106(4):241-8