Many potential reasons exist as to why patients do not achieve lipid
treatment goals. For example, some patients are never treated with any
lipid-altering drug. Patient noncompliance may also be a factor. Known,
potential, or perceived issues of tolerability and safety of high-dose
statins among clinicians and patients may pose therapeutic challenges.
the resistance among many clinicians to use the highest doses of
statins alone is due to not only concerns about toxicity and
intolerability (which most often occur at higher doses), but also the
recognition that most LDL-C reduction with statins occurs at the lower
doses. In fact, each doubling of the statin dose produces an average
additional decrease in LDL-C levels of about 5–6%, based upon the
baseline LDL-C value ("rule of 6"). In the example above, atorvastatin
10 mg/day lowered mean LDL-C levels by 38%. Upon titration to 20 mg, 40
mg, and 80 mg, LDL-C levels were lowered only an additional 8%, 5%, and
3% respectively (based upon the baseline, pretreatment LDL-C level) for
a total further reduction of 16% with these three titrations. In other
words, starting with a mean baseline LDL-C level of 211 mg/dl,
atorvastatin 10 mg per day would be expected to lower LDL-C levels to
about 131 mg/dl (38% reduction). A three-step doubling of the dose to
atorvastatin 80 mg per day would lower the baseline mean LDL-C levels
an additional 16% to about 97 mg/dl (38% + 16% = 54% total reduction).
The modest percent reduction after the lowest doses is also seen with
the above simvastatin example, in which simvastatin 10 mg lowered mean
LDL-C levels by 28%, while titration to 20 mg and 40 mg resulted in
only an additional 7% and 6% reduction in LDL-C compared with the
Finally, many patients with more severe
dyslipidemias and/or in need of the most aggressive lipid therapy may
not achieve lipid treatment goals even when the highest dose of statin
is used. For all of these reasons, combination lipid-altering drug
therapy is often indicated to avoid known or potential toxicity with
higher doses of statin alone, or when statin monotherapy is
insufficiently effective at the higher doses.
- Bays H. Ezetimibe. Expert Opin Investig Drugs 2002;11:1587-1604.
- Illingworth DR. Management of hypercholesterolemia. Med Clin North Am 2000;84:23-42.
P, Kafonek S, Laurora I, Hunninghake D, for the CURVES Investigators.
Comparative dose efficacy study of atorvastatin versus simvastatin,
pravastatin, lovastatin, and fluvastatin in patients with
hypercholesterolemia (the CURVES study). Am J Cardiol 1998;81:582-587.