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'Very Low' Risk From Statin Cholesterol Drugs

Statin drugs, which lower dangerous cholesterol levels, have "very low risk" of kidney and severe muscle side effects, says Richard Karas, MD, PhD.

However, among available statins -- Crestor, Lipitor, Pravachol, and Zocor -- the FDA received more reports of those problems with Crestor during the drug's first year on the market, says Karas and colleagues in the online edition of Circulation.

Karas, who directs the Preventive Cardiology Center and the Women's Heart Center at Boston's Tufts-New England Medical Center, talked about the study at a news conference.

The news needs a big dose of perspective, he and other doctors said at the news conference. Those side effects were extremely rare and people should not stop taking their statin drugs without first consulting their physicians, they said.

'Very Safe' Drugs

High cholesterol is a major heart hazard, and heart disease is a leading cause of death for U.S. men and women. There are many steps to take to lower cholesterol, including a healthy diet and exercise. Millions of people also take medications to curb their cholesterol.

"Statins in general are very safe," said Scott Grundy, MD, PhD, at the news conference. "These can be lifesaving to high-risk patients."

Grundy works at the Center for Human Nutrition and the departments of clinical nutrition and internal medicine at the University of Texas Southwestern Medical Center in Dallas. He wrote an editorial for Circulation about the study.

"Statins are among our best drugs for treating individuals who have elevated cholesterol," says American Heart Association president Alice Jacobs, MD, in a news release. "This study should reassure the public that the drugs are safe. Overwhelmingly, the majority of individuals tolerate statins very well and the absolute risk of side effects is low, including for [Crestor]."

AstraZeneca Pharmaceuticals, the maker of Crestor, did not respond to a request for comment in time for publication. AstraZeneca is a WebMD sponsor.

Screening Recommended Before Prescription

Most of the muscle and kidney side effects occurred in people who were particularly vulnerable to those problems and generally went away when the medications were stopped, said Grundy. He encourages doctors to screen for risk factors before prescribing any statin.

Patients should also talk to their doctors about any issues that come up, such as brown urine, an indication that muscle damage or liver problems may be occurring. Also, "very dramatic [muscle pain] that doesn't go away" is something Karas recommends that patients should discuss with their doctors. Those may be symptoms of a severe and potentially fatal condition called rhabdomyolysis, in which massive muscle damage occurs.

The following conditions are listed as carrying a higher risk of muscle damage from statin drugs, which require either avoidance of the drugs or use of a lower dose:

-- Older age, especially greater than 80 (women more than men)
-- Small frame and frailty
-- Multiple chronic medical conditions, such as chronic kidney failure (especially with diabetes)
-- Use of multiple medications that may change the metabolism of the statin drug, especially antifungal drugs
-- People who drink large amounts of grapefruit juice (more than one quart per day), which alters the metabolism of statin drugs
-- Alcohol abuse

Because each person is different, doctors and patients should know and discuss the risks and benefits before choosing a statin, Grundy told reporters. Cholesterol-lowering statin drugs include information about possible rare muscle or kidney problems in their prescription information; the possible risk isn't a new discovery.

Study's Findings

Karas and colleagues looked at muscle and kidney problems reported to the FDA during Crestor's first year on the market (starting in the latter half of 2003).

During that time, there were 28 such side effects per million Crestor prescriptions, 13 per million Zocor prescriptions, 3.5 per million Pravachol prescriptions, and 4.3 per million Lipitor prescriptions, says Karas.

Deaths were extremely rare for all of the statins.

Because reported side effects might be different during a drug's first year, they also checked reports for the three older drugs -- Pravachol, Lipitor, and Zocor -- in their first year of release. Crestor's number was higher than those drugs during their first year but lower than that of another statin, Baycol, which was pulled form the market in 2001.

Baycol was taken off the market because of concerns about deaths related to rhabdomyolysis.

FDA and Crestor

In March, the FDA issued a public health advisory about Crestor's potential risks and benefits. That followed a January 2005 report by AstraZeneca that a patient died while taking Crestor.

After an extensive review, the FDA said that patients taking recommended doses of Crestor had a similar risk of rhabdomyolysis as other statin drugs. Grundy praised the FDA's review in his editorial.

In March, an AstraZeneca news release said the FDA's letter stated that "all of the available evidence indicates that Crestor does not pose a risk of muscle toxicity greater than the other approved statins, and that with respect to renal toxicity, there is no convincing evidence that Crestor poses a serious risk of renal injury.

"Recently, the FDA approved revisions to the Crestor prescribing information, which strengthened language around the appropriate use of Crestor," the release continues. "At the same time, the FDA issued a statement confirming that the potential benefits of Crestor outweigh the potential risks when taken as directed."

Report Database Has Pros, Cons

The FDA's record of reported adverse events isn't perfect. Reports are voluntary, and doctors may have stepped up their reporting or awareness in the wake of Baycol's problems, said Karas and Grundy.

However, because those reports can be tallied with millions of prescriptions, they said it's the closest thing they have to a national side effect reporting system once a drug is on the market.

Reports Don't Prove Drugs Were Responsible

Reports to the FDA don't prove that the drugs were responsible for the problems, and Crestor wasn't found to have greater risk at the recommended dose (40 milligrams) in preapproval studies of more than 12,000 people, said Grundy.

Karas has received research grants and served on the speaker's bureau for AstraZeneca. The grants did not include this study. Grundy has also consulted for or received research grants from several major pharmaceutical companies, including AstraZeneca and makers of other statin drugs.

By Miranda Hitti, reviewed by Brunilda Nazario, MD

SOURCES: Richard Karas, MD, PhD, director, Preventive Cardiology Canter and Women's Heart Center, Boston's Tufts-New England Medical Center. Scott Grundy, MD, PhD, Center for Human Nutrition; departments of clinical nutrition and internal medicine, University of Texas Southwestern Medical Center, Dallas. Alice Jacobs, MD, president, American Heart Association. Alsheikh-Ali, A. Circulation, May 23, 2005, online edition. Grundy, S. Circulation, May 23, 2005, online edition. WebMD Medical News: "FDA Updates Crestor Warning Information."