Should we lower cholesterol as much as possible?

Ravnskov et al. raise concerns about the safety of high-dose statins
[1].

A recent retrospective analysis of pooled data from 49 clinical
trials of atorvastatin (n=14,236 patients) has shown that the incidence of
treatment-associated adverse events for high-dose atorvastatin (80 mg) is
similar to that of atorvastatin at a dose of 10 mg and placebo. Based on
this analysis, the safety profile of atorvastatin at the highest dose is
supported [2].

However, a recent meta-analysis (n=71,108) of randomized controlled
trials have shown that atorvastatin is associated with the greatest risk
of adeverse events among atorvastatin, fluvastatin, lovastatin,
simvastatin, and pravastatin [3].

On the other hand, though we analyzed the incidence of
rhabdomyolysis, based on Japanese post-marketing survey for pitavastatin
as a new statin [4], the incidence was 0 (95% CI: 0-12.9) per 10,000
person-years in monotherapy of pitavastatin (n=7,880). Furthermore,
pitavastatin (2 mg/day) decreased the risk of any adverse events
significantly compared with simvastatin (20 mg/day) in (p=0.015 by using
Fisher exact test), though the mean rate of low density lipoprotein (LDL)
cholesterol reduction was not significantly different (pitavastatin:
38.2%, simvastain: 39.4%) [5]. Therefore, these studies indicate the rate
of adverse events differs among statins.

On the other hand, though we think that there are the benefits of
high-dose statins in the secondary prevention of cardiovascular diseases,
the benefits are not sufficiently shown in the primary prevention of
cardiovascular diseases. Furthermore, the worries about the increase of
high-dose statins-related adverse events remain even in the secondary
prevention of cardiovascular diseases [1].

Therefore, statins should be used, considering the difference of the
rate of adverse events among statins in the primary or the secondary
prevention of cardiovascular diseases. Furthermore, it should be still
avoided to use high-dose statins in the primary prevention of
cardiovascular diseases.

References:

[1] Ravnskov U, Rosche PJ, Sutter MC and Houston MC. Should we lower
cholesterol as much as possible ? BMJ 2006;332:1330-1332.

[2] Newman C, Tsai J, Szarek M, Luo D, Gibson E, Comparative safety
of atorvastatin 80 mg versus 10 mg derived from analysis of 49 completed
trials in 14,236 patients, Am J Cardiol 2006;97: 61-67.

[3] Silva MA, Swanson AC, Gandhi PJ, Tataronis GR, Statin-related
adverse events: a meta-analysis. Clin Ther 2006;28:26-35.

[4] Kurihara Y., Douzono S.,Fujita S., Kakuda T., Nachi S., Uematsu
H. Interim Report, 8083 Patients on the Drug Use Investigation of
Pitavastatin (LIVALO Tablet), Jpn Pharmacol Ther 2006;34:317-326. (in
Japanese)

[5] Park S, Kang HJ, Rim SJ, et al, A randomized, open-label study to
evaluate the efficacy and safety of pitavastatin compared with simvastatin
in Korean patients with hypercholesterolemia, Clin Ther 2005;27:1074-1082.

Competing interests:
None declared