RESEARCH - Cholesterol drug Crestor poses risks, journal says

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Cholesterol Drug Crestor Poses Risks, Journal Says

Study Suggests Use Only as Last Resort

By Marc Kaufman

Washington Post Staff Writer

Tuesday, May 24, 2005; Page A01

The powerful cholesterol-lowering drug Crestor is significantly more likely

than other statins to cause muscle deterioration that can lead to kidney

disease and failure, according to a study in the American Heart

Association's journal, Circulation.

The conclusion is at odds with the most recent recommendation of the Food

and Drug Administration, which in March rejected a citizen's petition to

remove Crestor from the market. At the time, the FDA said Crestor, which has

been aggressively marketed by AstraZeneca LP, appeared to be no more

dangerous than other statins for most people.

Based on the number of side effects reported to the FDA, however, the

researchers said yesterday that Crestor was two to six times as likely to

cause complications over a one-year period as three other statins on the

market.

Although the number of serious side effects reported by Crestor users was

small, the study authors said the higher rate convinced them that doctors

should try their patients on other statins and only turn to Crestor as a

last resort.

The study " raises concerns about the safety of this drug at the range of

doses used in common clinical practice, " the study concludes. " It would seem

prudent at the current time for health care providers to consider other

statins as first-line therapy. "

AstraZeneca defended its billion-dollar-a-year drug, saying " we strongly

disagree with the conclusions of this study. " In a statement, the company

said the FDA's voluntary system for soliciting reports of complications,

called " adverse events, " does not confirm the accuracy of the accounts it

gets and so cannot be used to determine a drug's risks.

The company cited the FDA's recent conclusion that based on all the evidence

available, Crestor does not pose an unacceptable risk. " AstraZeneca again

reaffirms that the safety profile of Crestor is in line with other marketed

statins, and is a highly effective cholesterol-lowering therapy, " it said.

With drug safety an increasingly hot topic with the public, doctors and

members of Congress, the Circulation paper quickly became a new source of

controversy.

Sidney M. Wolfe of Public Citizen Health Research Group, who filed the

petition rejected by the FDA, said the study confirmed his conclusions.

" This should be very embarrassing to the FDA, " Wolfe said. He said that

unlike the arthritis painkillers Vioxx and Bextra, which were recently taken

off the market because of harmful side effects, Crestor's potential to cause

muscle and kidney damage was known before the drug was approved.

" Short of having the drug taken off the market, I don't think that anything

could contribute to the end of a drug more than this paper, " Wolfe said.

M. Grundy, a University of Texas Southwestern Medical Center

researcher long associated with efforts to reduce cholesterol levels to

prevent heart disease, defended the drug. Grundy, in a commentary

accompanying the research paper, said he was not convinced that the risks

from the higher potency of Crestor outweighed its possible benefits to

patients with especially high cholesterol levels.

The American Heart Association -- which did not take a position on either

the study or the accompanying commentary -- held a teleconference yesterday

to discuss the study and its view that patients should continue on whatever

statins their doctors prescribe. Grundy said he would prescribe Crestor now

as readily as any other statin. But H. Karas of Tufts-New England

Medical Center, lead author of the Circulation paper, said he would

recommend Crestor only as a last resort.

Both Karas and Grundy have received research contracts and speaking fees

from statin makers, including AstraZeneca. The heart association also

receives considerable financial support from drug companies.

Crestor, which was approved by the FDA in 2003, is agreed to be the most

potent statin on the market. Its higher strength, however, does not make a

dramatic difference in studies. While statins such as Lipitor, Zocor and

Pravachol lower LDL -- or harmful -- cholesterol by 50 to 55 percent,

Crestor decreases it by 55 to 60 percent, said Grundy and Karas.

In the new study, doctors of patients taking Crestor were significantly more

likely to report complications of kidney disease and rhabdomylosis, a muscle

deterioration that releases toxins into the blood that can cause renal

failure. The overall number was small -- 145 muscle or kidney problems out

of 5.2 million prescriptions during the drug's first year on the market --

but the number was substantially higher than for other statins.

In 2001, the FDA took Baycol, a considerably more powerful statin than

Crestor, off the market because of similar side effects. In a congressional

hearing last December, FDA drug safety officer and whistle-blower

Graham identified Crestor as one of five drugs now on the market that he

believed posed serious safety problems that were not balanced by their

benefits.

The FDA yesterday referred callers to its March conclusions that Crestor is

no more hazardous than other statins.

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