PFPC Daily - May 28, 2005

Alsheikh-Ali AA, Ambrose MS, Kuvin JT, Karas RH - "The Safety of
Rosuvastatin as Used in Common Clinical Practice. A Postmarketing
Analysis" Circulation. 2005 May 23; [Epub ahead of print]

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.