Rosuvastatin (
Crestor), an
HMG-CoA reductase inhibitor (
statin), has a favorable pharmacologic profile, including its selective uptake by hepatic cells, hydrophilic nature, and lack of metabolism by
cytochrome p450 (CYP) 3A4
isoenzyme. This last property means that the potential for CYP3A4-mediated drug interactions and, as a consequence, adverse events is low in those requiring concomitant
therapy with a
statin and agents metabolized by
CYP3A4. In a broad spectrum of adult patients with
dyslipidemias, oral
rosuvastatin 5-40 mg once daily effectively and rapidly improved
lipid profiles in several large, randomized, mainly double-blind, multicenter trials of up to 52 weeks' duration. After 12 weeks' treatment,
rosuvastatin was significantly (all p < 0.05) more effective at milligram equivalent dosages than
atorvastatin,
pravastatin, and
simvastatin in improving the overall
lipid profiles of patients with
hypercholesterolemia (intent-to-treat analyses). Moreover, overall a significantly (all p < 0.001) higher proportion of patients achieved National
Cholesterol Education Program (NCEP) Adult Treatment Panel (
ATP) III
low-density lipoprotein-cholesterol (
LDL-C) goals with
rosuvastatin 10 mg/day than with therapeutic starting dosages of these other
statins after 12 weeks' treatment in pooled analyses.
Rosuvastatin treatment for up to 52 weeks was generally well tolerated in patients with
dyslipidemias in clinical trials. The most commonly reported treatment-related adverse events were
myalgia,
constipation,
asthenia,
abdominal pain, and
nausea; these were mostly transient and mild. The incidence of
proteinuria or microscopic
hematuria with
rosuvastatin 10 or 20 mg/day was <1% versus <1.5% with
rosuvastatin 40 mg/day; these events were mostly transient and not associated with acute or progressive deterioration in renal function at recommended dosages. Importantly, very few patients experienced elevations in serum
creatine phosphokinase (CPK) levels of over [corrected] 10-fold the upper limit of normal (0.2-0.4% of patients) or treatment-related
myopathy (<or=0.1%) [i.e. muscle
aches or weakness plus the same elevated serum CPK levels] at dosages of 5-40 mg/day. In conclusion,
rosuvastatin treatment effectively and rapidly improves the
lipid profile in patients with a broad spectrum of
dyslipidemias. In those with
hypercholesterolemia (including high-risk patients),
rosuvastatin was more efficacious than and generally as well tolerated as
atorvastatin,
simvastatin, and
pravastatin, with significantly more
rosuvastatin recipients achieving their NCEP
ATP III target
LDL-C levels. Thus,
rosuvastatin has emerged as a valuable choice for first-line treatment in the management of low- to high-risk patients requiring
lipid-lowering
drug therapy.