Significant numbers of patients at risk for
coronary heart disease (CHD) fail to reach National
Cholesterol Education Program (NCEP)-designated
low density lipoprotein cholesterol (
LDL-C) goals in spite of the wide range of currently available treatments, including combination
therapies.
Ezetimibe, the first in a class of novel
cholesterol absorption inhibitors, demonstrated
lipid-lowering and antiatherosclerotic activity in experimental and clinical
hypercholesterolemia. Studies in hypercholesterolemic dogs showed that
ezetimibe coadministered with
statins caused greater
lipid-lowering effects compared to either
drug alone. These effects were confirmed in clinical studies of patients with primary
hypercholesterolemia where initiation of treatment with
ezetimibe plus a
statin, or addition of
ezetimibe to ongoing
statin therapy, produced significant incremental reductions in
LDL-C, as well as incremental increases in
high-density lipoprotein cholesterol (HDL-C) and reductions in
triglyceride levels. Combination
therapy also significantly increased the number of patients attaining
LDL-C goal at the end of treatment, compared to
statin monotherapy. In studies using
simvastatin,
atorvastatin,
pravastatin, and
lovastatin, addition of
ezetimibe to low dose
statin was as effective
as a 2- to 3-fold upward titration of the corresponding
statin dose.
Ezetimibe-
statin combination
therapy provided similar improvements in patients with primary
hypercholesterolemia, as well as with heterozygous and
homozygous familial hypercholesterolemia.
Ezetimibe monotherapy effectively reduced plasma
campesterol and
sitosterol in patients with homozygous
sitosterolemia. Clinical studies showed that
ezetimibe was well tolerated, with a safety profile comparable to placebo when administered as monotherapy and comparable to
statin alone when coadministered with a
statin. These data provide strong evidence that, through their complementary
lipid-lowering mechanisms,
ezetimibe coadministered with a
statin offers an effective combination treatment option for patients with
hypercholesterolemia, including those with genetically inherited disease.