Literature

Adequate effectivity long-acting statins with morning intake

27-6-2017 • Awad K, et al. J Clin lipidol, 2017  

Effects of Morning Versus Evening Statin Administration on Lipid Profile: A Systematic Review and Meta-Analysis


Awad K, Serban MC, Penson P, et al.
Journal of Clinical Lipidology 2017; published online ahead of print
 

Introduction and Methods 

Statins reduce elevated levels of plasma cholesterol very effectively and are beneficial for the primary and secondary prevention of cardiovascular disease [1-3]. Usually, they are administrated in the evening, since cholesterol biosynthesis peaks during the night and most statins have short half-lives. However, the optimal timing of administration in terms of efficacy and patient compliance is not known [4,5].
 
In this systematic review and meta-analysis, the different effects of morning and evening statin administration on lipid profiles were evaluated, in order to find the dosing regimen with the highest therapeutic efficacy. For this purpose, studies were included if they 1) were prospective or retrospective clinical controlled studies (randomized or not), 2) compared the effects of morning administration against evening administration of statin therapy on total cholesterol TC, LDL-C, HDL-C or triglycerides (TG) or reported sufficient information on blood lipid levels at baseline and at the end of study in both groups, 3) reporting the net change scores or the mean difference between the change scores of the 2 groups (primary outcome). The secondary outcome was compliance of patients.
 

Main results

  • Only 11 articles published between 1986 and 2014 were eligible for the meta-analysis: these included 12 treatment arms and 1034 participants, with a study duration of 4 to 12 weeks. Statin doses used were: 40 mg/d atorvastatin, 2.5 to 20 mg/d simvastatin, 10 mg/d rosuvastatin, 20 mg/d lovastatin, 40 mg/d pravastatin and 80 mg/d fluvastatin.
  • The overall pooled analysis comparing effects of morning vs evening administration of statins on TC, HDL-C and TG were not statistically significant, but it favored the evening administration of statins on LDL-C. Mean differences were: TC: 1.68 mg/dL (95% CI: -0.33 to 3.69; P=0.10), HDL-C: 0.05 mg/dL (95% CI: -0.77 to 0.87; P=0.90), TG: 1.66 mg/dL (95% CI: -2.68 to 5.99; P=0.45) and LDL-C: 3.24 mg/dL (95% CI: 1.23–5.25; P=0.002).
  • The pooled analysis of the short half-life statins subgroup did not reveal any significant difference between the morning-dose and evening-dose groups in terms of HDL-C and TG, but it favored the evening dose over the morning dose in terms of TC and LDL-C. Mean differences were: HDL-C: 0.28 mg/dL ( 95% CI: -1.49 to 2.06; P=0.75), TG: 0.97 mg/dL (95% CI: -13.54 to 15.48; P=0.90), TC: 12.10 mg/dL (95% CI: 5.25–18.95; P=0.0005), LDL-C: 9.68 mg/dL (95% CI: 3.32 -16.03; P=0.003).
  • The pooled analysis of the long half-life statins subgroup did not show any significant difference for TC, HDL-C or TG, but it slightly favored the evening dose over the morning dose for LDL-C. Mean differences were: TC: 0.70 mg/dL (95% CI: -1.40 to 2.80; P=0.51), HDL-C: -0.01 mg/dL (95% CI: -0.94 to 0.92 P=0.98), TG: 1.72 mg/dL (95% CI: -2.82 to 6.27; P=0.46), LDL-C: 2.53 mg/dL (95% CI: 0.41–4.64; P=0.02).  
  • Out of 3 studies that reported compliance rates, 1 study indicated that compliance was better when treatment was taken in the morning, compared with the evening, whereas the other 2 studies were neutral in terms of compliance.
 

Conclusion

Short-acting statins are significantly more effective in lowering LDL-C and TC when they are administered in the evening, rather than the morning, whereas long-acting statins had a nearly equivalent efficacy irrespective of timing of administration during the day, with the exception of a small but statistically significant effect on LDL-C. These findings confirm that short-acting statins should be taken in the evening and the authors suggest that long-acting statins can also be taken in the morning, if this facilitates patient compliance.
 
Find this article online at J Clin Lipidol
 

References

1. Pedersen TR, Olsson AG, Faergeman O, et al. Lipoprotein changes and reduction in the incidence of major coronary heart disease events in the Scandinavian Simvastatin Survival Study (4S). Circulation.
1998;97(15):1453–1460.
2. Mabuchi H, Kita T, Matsuzaki M, et al. Large scale cohort study of the relationship between serum cholesterol concentration and coronary events with low-dose simvastatin therapy in japanese patients with hypercholesterolemia and coronary heart disease. Circ J. 2002;66(12): 1096–1100.
3. Sacks FM, Pfeffer MA, Moye LA, et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. N Engl J Med. 1996;335(14):1001–1009.
4. Parker TS, McNamara DJ, Brown C, et al. Mevalonic acid in human plasma: relationship of concentration and circadian rhythm to cholesterol synthesis rates in man. Proc Natl Acad Sci U S A. 1982;79(9):3037–3041.
5. Jones PJ, Schoeller DA. Evidence for diurnal periodicity in human cholesterol synthesis. J Lipid Res. 1990;31(4):667–673.


 


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