Crestor Doesn't Help Dialysis Patients

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    * MARCH 30, 2009, 12:15 P.M. ET

Crestor Doesn't Help Dialysis Patients

By Peter Loftus
Of DOW JONES NEWSWIRES

ORLANDO, Fla. (Dow Jones)--AstraZeneca PLC's (AZN) Crestor cholesterol-lowering drug failed to reduce the risk of heart attacks, deaths and strokes in people with kidney failure, a new study found.

The study is a setback in AstraZeneca's efforts to find new uses for the blockbuster drug, though it follows recent positive studies that suggest other new benefits and a broader target population for Crestor. The results were presented Monday at the annual scientific meeting of the American College of Cardiology here.

The failure of the Crestor trial also could have implications beyond AstraZeneca. Merck & Co. (MRK) and Schering-Plough Corp. (SGP) are conducting a large study of their combination cholesterol drug Vytorin to see if it can prevent heart disease and strokes in kidney-disease patients, versus one of its components alone, simvastatin. The 9,000-patient "Sharp" trial started in 2003 and is expected to finish in 2010.

It's possible the outcome of the Crestor study could force a modification of the Vytorin study. An editorial published online Monday in The New England Journal of Medicine suggested the committees of researchers overseeing the Vytorin trial now should consider the results of the Crestor study and "form a view on the science and ethics of continuing the study."

Colin Baigent, an Oxford University researcher and lead investigator of the Vytorin trial, told Dow Jones Newswires a data-monitoring committee will review the Crestor results and advise the trial's lead committee on whether any modifications to the trial are necessary.

Rory Collins, another Oxford researcher who chairs the steering committee of the Vytorin trial, said he thought the larger size and longer duration of the trial would mitigate the need for any significant changes. The Crestor results "endorse exactly what Sharp is doing," he said.

Vytorin sales have taken a hit since studies released last year raised questions about its efficacy and safety, and investors are closely watching the progress of ongoing Vytorin studies that will shed more light on whether it helps reduce heart attacks. Bernstein analyst Tim Anderson recently said there was a good chance the Sharp trial would fail.

Crestor and other statin drugs are mainly used to lower cholesterol in people at risk for heart attacks and related diseases. But it's been unclear whether they can reduce heart problems in people with kidney failure undergoing hemodialysis, a procedure that essentially cleans out the blood. Such patients have an increased risk of premature heart disease.

A prior study showed Pfizer Inc.'s (PFE) Lipitor statin didn't significantly help people with type 2 diabetes undergoing dialysis.

The new Crestor study, titled "Aurora," enrolled about 2,780 people ages 50 to 80 years old who were undergoing maintenance hemodialysis. About half received Crestor once daily, while the other half took a fake pill.

Although Crestor reduced levels of bad cholesterol, it didn't reduce the combined rate of death from cardiovascular causes, heart attack or stroke, versus placebo, according to data published online Monday by The New England Journal of Medicine. Some 396 patients in the Crestor group experienced these events during an average follow-up period of nearly four years, versus 408 in the placebo group, a statistically insignificant difference.

The rates of adverse events such as infection and musculoskeletal disorder were relatively similar between Crestor and placebo.

The researchers who led the study suggested Crestor didn't work because cardiovascular disease in patients on dialysis differs from that in other patients.

An accompanying editorial published in NEJM noted that coronary lesions usually cause cardiac disease in the general population, whereas a large majority of dialysis patients have other conditions such as calcified aortic valves and enlarged heart muscle. It could be that the benefits of lowering bad cholesterol don't transfer from the general population to dialysis patients.

Alex Gold, executive director of clinical development at AstraZeneca, said the Aurora results show that a "global public-health challenge remains and appears very difficult to address."

Crestor sales rose 29% to $3.6 billion last year.

-By Peter Loftus, Dow Jones Newswires; 215-656-8289; peter.loftus@dowjones.com

http://online.wsj.com/article/BT-CO-20090330-711056.html#