Atorvastatin in the treatment of primary hypercholesterolemia and mixed dyslipidemias.
OBJECTIVE
To review the efficacy and safety of atorvastatin in the treatment of dyslipidemias.


METHODS
A MEDLINE search (January 1960-April 1998), Current Contents search, additional references listed in articles, and unpublished data obtained from the manufacturer were used to identify data from scientific literature. Studies evaluating atorvastatin (i.e., abstracts, clinical trials, proceedings, data on file with the manufacturer) were considered for inclusion.


METHODS
English-language literature was reviewed to evaluate the pharmacology, pharmacokinetics, therapeutic use, and adverse effects of atorvastatin. Additional relevant citations were used in the introductory material and discussion.


METHODS
Open and controlled animal and human clinical studies published in the English-language literature were reviewed and evaluated. Clinical trials selected for inclusion were limited to those in human subjects and included data from animals if human data were not available.


RESULTS
Atorvastatin is a recent hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor for the treatment of primary hypercholesterolemia, mixed dyslipidemias, and homozygous familial hypercholesterolemia. In patients who have not met the low-density lipoprotein cholesterol (LDL-C) goal as recommended by the National Cholesterol Education Program Adult Treatment Panel II guidelines, atorvastatin 10-80 mg/d may be used as monotherapy or as an adjunct to other lipid-lowering agents and dietary modifications. In placebo-controlled clinical trials, atorvastatin 10-80 mg/d lowered LDL-C by 35-61% and triglyceride (TG) concentrations by 14-45%. In comparative trials, atorvastatin 10-80 mg/d showed a greater reduction of serum total cholesterol (TC), LDL-C, TG concentrations, and apolipoprotein B-100 (apo B) compared with pravastatin, simvastatin, or lovastatin. In comparison, currently available HMG-CoA reductase inhibitors (lovastatin, simvastatin, pravastatin, fluvastatin, cerivastatin) lower LDL-C concentrations by approximately 20-40% and TG concentrations by approximately 10-30%. In pooled placebo-controlled clinical trials of up to a duration of 52 weeks, atorvastatin in dosages up to 80 mg/d appeared to be well tolerated. The most common adverse effect of atorvastatin was gastrointestinal upset. The incidence of elevated serum hepatic transaminases may be greater at higher dosages of atorvastatin. The risk of myopathy and/or rhabdomyolysis is increased when an HMG-CoA reductase inhibitor is taken concomitantly with cyclosporine, gemfibrozil, niacin, erythromycin, or azole antifungals.


CONCLUSIONS
Atorvastatin appears to reduce TC, LDL-C, TG concentrations, and apo B to a greater extent than do currently available HMG-CoA reductase inhibitors. Atorvastatin may be preferred in patients requiring greater than a 30% reduction in LDL-C or in patients with both elevated LDL-C and TG concentrations, which may obviate the need for combination lipid-lowering therapy. Adverse effects of atorvastatin appear to be similar to those of other HMG-CoA reductase inhibitors and should be routinely monitored. Long-term safety data (> 1 y) on atorvastatin compared with other HMG-CoA reductase inhibitors are still needed. Cost-effectiveness studies comparing atorvastatin with other HMG-CoA reductase inhibitors remain a subject for further investigation. Published clinical studies evaluating the impact of atorvastatin on cardiovascular morbidity and mortality are still needed. Additionally, clinical studies evaluating the impact of lipid-lowering therapy in a larger number of women, the elderly (> 70 y), and patients with diabetes for treatment of primary and secondary prevention of coronary heart disease are needed.
Yee
H S
HS
Pharmacy Service, Department of Veterans Affairs Medical Center, San Francisco, CA 94121, USA.
Fong
N T
NT
D000818:Animals; D000924:Anticholesteremic Agents / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use*; D000069059:Atorvastatin; D002986:Clinical Trials as Topic; D006538:Heptanoic Acids / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use*; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy*; D006949:Hyperlipidemias / Q000188:drug therapy*; D011758:Pyrroles / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use*; D016896:Treatment Outcome
D000924:Anticholesteremic Agents; D006538:Heptanoic Acids; D011758:Pyrroles; D000069059:Atorvastatin