Clinical

CORRECTION: Atorvastatin appears safe at high doses

Last Updated: 2006-02-27 7:53:40 -0400 (Reuters Health)

[Corrects story posted Feb 20, 2006. Amends dosage group in paragraph 6, changing "...three in the atorvastatin 20 mg group..." to "...three in the atorvastatin 10 mg group..."]

NEW YORK (Reuters Health) - A high dose of atorvastatin (80 mg) has a safety profile similar to that of a lower dose of the drug (10 mg), results of a meta-analysis show.

For patients at very high risk for coronary heart disease, the National Cholesterol Education Panel recommends aggressive lowering of low-density lipoprotein cholesterol. According to Dr. Connie Newman and colleagues at Pfizer Global Pharmaceuticals in New York, physicians may be concerned about prescribing statins at the doses required to meet these recommendations.

To assess the safety of the drug at the different doses, Dr. Newman's group pooled data from 49 clinical trials conducted between 1992 and 2004, which included data for 14,236 patients treated for an average of 2 weeks to 52 months. Treatment comprised atorvastatin 10 mg (n = 7258), atorvastatin 80 mg (n = 4798), or placebo (n = 2180).

Overall, the adverse event profiles for the three groups were similar, the authors report in the American Journal of Cardiology for January. There were actually more serious, nonfatal adverse events documented in the placebo group (134.5/1000 patient-years) than in either atorvastatin group (92.0/1000 in the 10 mg group and 82.2/1000 in the 80 mg group).

Rhabdomyolysis, a particular concern with statin treatment, was not observed in any of the patients.

Persistent elevations in alanine aminotransferase and aspartate aminotransferase > 3 times the upper limit of normal were documented in one patient in the placebo group, three in the atorvastatin 10 mg group, and two in the atorvastatin 80 mg group. Five patients receiving atorvastatin 80 developed hepatitis, which resolved within 4 weeks after discontinuing the drug.

The incidence of hematuria or albuminuria was low and similar in the two atorvastatin groups.

"The results of this analysis support the positive safety profile of atorvastatin at the highest dose," Dr. Newman and her colleagues conclude.

Am J Cardiol 2006;97:61-67.