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(Circulation. 2005;111:3051-3057.)
© 2005 American Heart Association, Inc.

Coronary Heart Disease

The Safety of Rosuvastatin as Used in Common Clinical Practice

A Postmarketing Analysis

Alawi A. Alsheikh-Ali, MD; Marietta S. Ambrose, MD; Jeffrey T. Kuvin, MD; Richard H. Karas, MD, PhD

From the Molecular Cardiology Research Institute and Division of Cardiology, Department of Medicine, Tufts-New England Medical Center, and Tufts University School of Medicine, Boston, Mass.

Reprint requests to Richard H. Karas, MD, PhD, Molecular Cardiology Research Institute, Box 80, Tufts-New England Medical Center, 750 Washington St, Boston, MA 02111. E-mail rkaras{at}tufts-nemc.org

Received April 15, 2005; revision received April 29, 2005; accepted May 2, 2005.

Background— Statins are currently the mainstay of dyslipidemia management for the primary and secondary prevention of cardiovascular disease. Controversial concerns about the safety of the newly marketed statin rosuvastatin have been raised on the basis of premarketing studies and a few postmarketing reports.

Methods and Results— We reviewed rosuvastatin-associated adverse events reported to the US Food and Drug Administration over its first year of marketing. On the basis of prescription data obtained from IMS Health, rates of adverse event reports (AERs) per million prescriptions were calculated. Rates of rosuvastatin-associated AERs over its first year of marketing were compared with those seen with atorvastatin, simvastatin, and pravastatin over the concurrent timeframe and during their respective first years of marketing. Comparison was also made to the first year of marketing of cerivastatin. The primary analysis examined the composite end point of AERs of rhabdomyolysis, proteinuria, nephropathy, or renal failure. With either timeframe comparison, rosuvastatin was significantly more likely to be associated with the composite end point of rhabdomyolysis, proteinuria, nephropathy, or renal failure AERs. Reported cases of rhabdomyolysis, proteinuria, or renal failure tended to occur early after the initiation of therapy and at relatively modest doses of rosuvastatin. The increased rate of rosuvastatin-associated AERs relative to other widely used statins was also observed in secondary analyses when other categories of AERs were examined, including adverse events with serious outcomes, liver toxicity, and muscle toxicity without rhabdomyolysis.

Conclusions— The present analysis supports concerns about the relative safety of rosuvastatin at the range of doses used in common clinical practice in the general population.

Key Words: cholesterol • complications • drugs • lipids • population

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