The Specialist Forum Volume 13 No 11 November 2013 | Page 82

CHOLESTEROL

versus 38% in the daily therapy group. It should be noted that the
initial dose of atorvastatin had to be doubled at the six week followup in 79% of patients in the alternate-day therapy group compared
with 17% of patients in the daily therapy group. Target LDL-C goal
was met in 43% of the patients in the alternate-day therapy group
and in 75% of the daily therapy group.
• In their study, involving patients with and without ischaemic heart
disease, three groups were randomised to receive either 10mg of
atorvastatin every other day, or 10mg every day or 20mg every other
day for a total of six weeks, Jafari et al showed that the absolute
reduction of LDL-C was significantly lower in patients taking ator­ a­
v
statin 20mg every other day compared with the other two groups.
According to Marcus, this study illustrates the importance of using
the same patients for comparison rather than comparing drug regimens in different groups.
• Wongwiwatthananukit et al showed that 70% of patients who received 10mg of rosuvastatin every other day, achieved LDL-C goal,
while 85% of patients receiving the drug once per day, achieved
goal. The percentage of patients who achieved LDL-C goals was not
significantly different in the two groups. Patients given the drug every
other day had a reduction of LDL-C of 39%, while those who received
the drug once per day had an LDL-C reduction of 48%.
• Ferrer-Garcia et al found that alternate-day dosing with 10mg of atorvastatin could be an effective alternative to daily dosing in some type
2 diabetic patients. LDL-C levels decreased by 23% after alternateday dosing and 39% after daily dosing with atorvastatin.
• A literature review by Reindl et al concluded that alternate-day statin
seems to be effective in reducing LDL-C, while potentially lowering
costs.

Is alternate day statin therapy as effective in
lowering high-sensitive CRP compared with
daily dosing?
The Justification for the Use of Statins in Primary Prevention: an
Intervention Trial Evaluating Rosuvastatin study indicated that the beneficial effect of statins to decrease cardiac events occurred primarily in
patients with elevated high-sensitivity C-reactive protein (CRP) levels.
Comparing the effect of 20mg of atorvastatin treatment given to
patients every other day or the same dose every day for three months,
Keles et al concluded that there was no difference in the percentage
decrease in LDL-C in both groups. The CRP levels were decreased by
22% in the patients treated on alternate days and by 35% in the patients
treated every day.
In a study involving 37 patients who were treated for primary and
secondary prevention with statins, Li et al showed that there was an
equal decrease in LDL-C and a 17% -18% reduction in high-sensitivity
CRP levels.

Can alternate-day dosing of statins decrease
the incidence of adverse effects?
Reported complications due to statin use include musculoskeletal pain
(11% of patients) and an increase in diabetes in some patients.
Musculoskeletal pain: some studies have shown that a nondaily
dosing of rosuvastatin or atorvastatin in patients with statin-induced
myalgia may be a reasonable strategy to treat musculoskeletal pain.
Marcus cautioned that there are no large prospective trials evaluating
this approach.
Diabetes: the US Food and Drug Administration (FDA) issued a

warning label for all statins earlier this year following the findings of
several studies that statins might be associated with an increase in
diabetes in some patients. However, noted Marcus, these studies
have not been able to determine with certainty whether this effect is
dose related. A more recent review of randomised controlled trials
suggested that alternate-day dosing could decrease statin-induced
hyperglycaemia and diabetes. More trials are needed to evaluate
whether the incidence of statin-induced diabetes would be decreased
in patients by comparing alternate-day dosing with daily dosing, wrote
Marcus.

Pleiotropic effects of statins
Several studies have confirmed the pleiotropic effects of statins. In a
recent review, the authors concluded that statins have a modest beneficial effect in reducing the incidence of sudden cardiac death. In addition, statins have been shown to reduce recurrent stroke or transient
ischaemic attacks as well as ‘possibly’ decreasing the incidence of
cancer after heart transplantation.
Based on observational studies that rosuvastatin decreases the
incidence of myocardial infarction and strokes in patients with elevated
high-sensitivity CRP levels (>2.0 mg/L) and other cardiac risk factors
even if they did not have an elevation in LDL-C, the FDA has approved
this indication for treatment with rosuvastatin in men over 50 and
women over 60 who have elevated high-sensitivity CRP levels and at
least one other traditional cardiovascular risk factor including hypertension, smoking, a family history of heart diseases, or low levels of highdensity lipoprotein cholesterol.
If some or many of the pleiotropic effects are dose related, intermittent dosing with statins would be a useful therapeutic strategy to possibly decrease costs and adverse effects of these drugs, noted Marcus.

Conclusions
The cholesterol-lowering action of alternate-day statins seems to be
as effective as daily dosing in many, but not all, individuals. Alternateday statins seem to reduce the side effects of statins and may be an
alternate way to treat increased levels of cholesterol in individuals who
cannot tolerate statins and would otherwise be unable to possibly
benefit from statin therapy. The alternate-day dosing of statins may
also be cost saving and could permit at least some treatment where
cost would otherwise prohibit treatment. The pleiotropic effects of
alternate-day statins are unknown and there are no outcomes data on
cardiovascular events.
References available on request.? CF

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November 2013 | Cardiology & Stroke Forum