Cardiovascular Disease / Crestor Caution - High Doses of Popular Cholesterol-Lowering Drug May Cause Muscle Disease

Safety problems with the widely used cholesterol drug Crestor have prompted European regulators to tighten prescription guidelines, but experts warn U.S. physicians may not be fully aware of the potentially deadly hazards for some of the more than 1 million American users of the drug.

Higher doses of Crestor, one of a family of cholesterol-lowering drugs known as statins, could increase risk of myopathy, a potentially life-threatening muscle disease that can affect the heart. In Europe, the drug's maker, AstraZeneca, changed the medication's label to warn doctors of the risk after cases of myopathy were reported there.

AstraZeneca notes these patients were already predisposed to having muscle disease. With the new label, patients who are prescribed Crestor must begin taking the drug at 10 milligrams. Dose increases to 20 milligrams or 40 milligrams — 40 milligrams being the highest dose available — will only be allowed if necessary, such as with patients with severely high cholesterol who are not at risk for muscle disease.

"It really relates to the issue of starting dose," explains Dr. Steven Nissen, vice-chairman of cardiology at The Cleveland Clinic Foundation. "If a person has high cholesterol you start at a higher dose. Now EU [the European Union] says don't ever start Crestor at a higher dose."

In the United States, the Food and Drug Administration is still reviewing reports it has received on the drug's association with muscle disease. But they do not currently have plans to change the U.S. labeling, stating, "these risk factors and many of the recommendations for how to minimize the risk of myopathy are already captured in the FDA- approved label."

Heeding the Warning

Doctors feel that the label change in Europe will affect how they prescribe Crestor. "I will avoid using the 40 milligrams, whereas in the past, I would put them on the top dose available," says Dr. Joe Breault, senior staff physician in Family Medicine at Ochsner Clinic Foundation in New Orleans, La.

Doctors agree side effects can occur with any cholesterol-lowering drug, including statins.

"Even though we know that there is contraindication in statins we may not pay attention to it in daily life. This warning will make us aware of it. It's a benefit of regulations." Breault says.

Dr. Michael Fleming, president of the American Academy of Family Physicians, also feels this new information will make him look at the drug even more closely. Fleming, who monitors FDA reports and is aware of the Crestor warning, says the warning makes him "more skittish about using it as opposed to other drugs."

Dr. Scott Grundy, director for the Center for Human Nutrition at the University of Texas Southwestern Medical Center in Dallas, attributes the greater risk of myopathy to the drug's high potency.

"Crestor is our most potent statin and thus it may well carry a higher risk for severe myopathy at high doses than other statins." says Grundy.

Dr. Peter Schulman of the University of Connecticut School of Medicine agrees. "Crestor is clearly a bit more of a potent cholesterol-lowering drug than any of its competitors such as Lipitor and Zocor," says Schulman. "And at every dose range from low to middle to high dose, it has about a 10 percent lowering advantage over Lipitor, its closest competitor in terms of lipid improvement."