The Specialist Forum Volume 13 No 11 November 2013 | Page 80

CHOLESTEROL

Alternate-day dosing with statins
Prof James Ker, Department of Internal Medicine, University of Pretoria

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tatins reduce synthesis of cholesterol in the liver and induce the
expression of low-density lipoprotein (LDL) receptors on the surface of the liver resulting in the reduction of circulating levels of
LDL-cholesterol (LDL-C). Stains also reduce the precursors of LDL, that
is, very low-density lipoproteins (VLDL). The duration of the cholesterollowering effect of the statins is not related to the pharmacokinetics of the
individual drug.
Steady-state statin drug levels may be achieved in a few days but
steady-state LDL reduction may take several weeks to achieve, it may
be six to eight weeks. After discontinuation of statins, there is a long
persistence of the effect of the statin and it takes several weeks for the
LDL level to return to baseline, and this effect is longer than would be
anticipated according to the pharmacokinetics of the statin.

but concluded that alternate dosing of statins seem to be effective in
reducing LDL-levels. A more recent review evaluating the lipid-lowering
effects of daily versus intermittent dosing of statins by Marcus was
published earlier this year.

Alternate-day statin therapy

By competitively inhibiting 3-hydroxy-3-methylglutaryl-coenzyme A
reductase inhibitors, statins are able to reduce synthesis of cholesterol
in the liver. This decrease in intracellular cholesterol concentration induces LDL receptor expression on the hepatocyte cell surface, leading
to an increase extraction of LDL-C from the blood and a decreased
concentration of circulating LDL-C and other apoliprotein B-containing
lipoproteins such as triglyceride-rich particles. In addition, statins may
influence LDL production by decreasing the production of LDL precursors such as VLDL lipoproteins and increasing catabolism of VDLDL
lipoprotein remnants.

There are a number of small, mostly non-randomised clinical trials on
the use of alternate-day statins. A review of the data was published
in 2010 and the author noted that the trials involved small numbers,

Review
The efficacy and safety of statins for primary and secondary prevention of cardiovascular disease (CVD) have been shown in a number of
studies. These studies have shown that the plasma concentration - not
cholesterol concentration - of atorvastatin can achieve a steady state
by day three with multiple dosing - a result that is consistent with a
mean elimination T ½ value in the 11- to 24-hour range.

Mechanism

Daily versus alternate-day statin dosing
The efficacy of alternate-day statin dosing has been confirmed by several studies. The most notable of these studies include:
• In a study involving 69 patients with mixed hyperlipidemia, receiving
either 10mg simvastatin and 250mg fenofibrate every other day, or
10mg simvastatin and 250mg fenofibrate every day, Kayikcioglu et
al showed that the LDL-C of patients in the first group decreased
by 35% compared to 36% in patients who were treated daily.
They noted no difference in the six-month LDL-C value when the
drugs were given on an alternate-day or daily basis. Patients in the
alternate-day therapy experienced less side effects (elevated serum
hepatic and muscle enzymes). However, the researchers stressed
that these differences were not statistical significance.
• In their review of alternate-day dosing, Metz and Lucas concluded
that although limited studies were available for review, there was a
trend toward benefit with alternate-day statin therapy.
• Piamsumboun et al showed a 32% decrease in LDL-C from
177±36mg/dL to 121 ± 34mg/dL in 60 patients treated with atorvastatin 10mg every other day for eight weeks. Treatment was introduced after diet control in patients who had hyperlipidemia failed.
Marcus pointed out that there was no comparison with daily d osing.
• Comparing alternate-day with daily dosing of atorvastatin for primary
and secondary prevention, Matalka et al found that the mean LDL-C
was reduced by 36% in the alternate-day therapy group and by 38%
in the daily therapy group. However, at week 12, the percentage decrease in mean LDL-C was 35% in the alternate-day therapy group
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November 2013 | Cardiology & Stroke Forum