Death May Be Rare Side Effect Common to All Cholesterol-Lowering Statins

By Daniel DeNoon
WebMD Medical News
Reviewed By Brunilda Nazario, MD
Jan. 11, 2005

A patient taking the cholesterol-lowering drug Crestor has died, the drug's manufacturer reported Monday.

The death occurred in December 2004. Initial reports indicate the patient died of a muscle-damaging disease linked to Crestor and all other members of the family of cholesterol-lowering drugs known as statins. The same side disease, rhabdomyolysis, drove the cholesterol-lowering drug Baycol off the market.

Rhabdomyolysis is a condition in which muscle cells break down. This floods the blood with muscle proteins, sometimes leading to fatal kidney failure.

Neither Crestor nor any of its sister drugs, which include Lipitor, Pravachol, and Zocor, is as deadly as Baycol was. But some experts say Crestor is more dangerous than the rest of the family. The watchdog group Public Citizen has petitioned the FDA to ban Crestor. And Crestor was one of five FDA-approved drugs named in congressional testimony by maverick FDA researcher David Graham as being unsafe.

It's not clear whether the Crestor patient actually died of rhabdomyolysis, says AstraZeneca spokeswoman Emily Y. Denney. AstraZeneca makes Crestor and is a WebMD sponsor.

"We have received a report of a patient death," Denney tells WebMD. "The initial report listed rhabdomyolysis, but additional follow-up shows the clinical picture to be quite complex. The reported symptoms are more in line with malignant neuroleptic syndrome than with rhabdomyolysis."

Patients with malignant neuroleptic syndrome may have rhabdomyolysis along with a very high temperature and rigidity, but it isn't a common side effect of statin drugs. It's linked to the use of some psychiatric medications.

Despite the death, Denney says Crestor's safety profile is similar to that of other cholesterol-lowering drugs.

"Even if it does turn out to be a case of rhabdomyolysis, it is a very rare side effect with all statins -- less than one case in 10,000 patients," Denney says. "Approximately 10% of these 1-in-10,000 cases are reported as fatal for all statins. The documentation of one such death for Crestor must be understood in the context that there are more than 14 million Crestor prescriptions in over 4 million patients."

Public Citizen's Sidney Wolfe, MD, says the data paint a much different picture. He notes that Crestor is linked not just to rhabdomyolysis but to direct kidney damage, he says.

"This drug causes primary renal failure. It is the only statin that does so," Wolfe tells WebMD. "Most of the cases are very low doses - 20 milligrams, 10 milligrams, and even 5 milligrams. No other statin does this -- it is uniquely dangerous. It is competing with Baycol. It causes kidney damage 75 times more often than all of the other statins combined."

Like Baycol, Wolfe says, Crestor is an extremely powerful drug.

"This drug is really potent. It lowers cholesterol -- and causes an inordinate amount of trouble," he says. "This idea you get magic benefits and not any more risk -- that just doesn't happen in the real world. And all you need to do is take two to four times more of the other statins to get the same cholesterol-lowering [effect], but without the unique risks of Crestor."

Richard Milani, MD, head of preventive cardiology at Ochsner Clinic in New Orleans, agrees that Crestor is very strong medicine.

"It is often used for patients with very severe [high cholesterol] that cannot be controlled by less potent statins," Milani tells WebMD. "Clearly it is used as the statin, maybe not of last resort, but for those who are most difficult to treat. We go to Crestor because it is such a big gun. It isn't in widespread use at this point because of concerns raised about safety. There are so many therapies that would treat milder [cholesterol problems]."

John P. Cooke, MD, PhD, professor of medicine and director of vascular medicine and biology at Stanford University, says Public Citizen is doing a good job of making people aware of potential drug hazards. But in a May 2004 interview, he said it was too soon to say that Crestor is particularly dangerous. Fortunately, clinical trials will soon provide more information.

"It is too soon to knock this drug off the market," Cooke told WebMD. "It has the potential to save lots of lives. So let's go forward with these clinical trials and see what the answer is."

SOURCES: Emily Y. Denney, spokeswoman, AstraZeneca. Sidney M. Wolfe, MD, director, Public Citizen Health Research Group. Richard Milani, MD, section head, preventive cardiology, Ochsner Clinic, New Orleans. John P. Cooke, MD, PhD, professor of medicine; and director of vascular medicine and biology, Stanford University, interviewed May 18, 2004.

http://my.webmd.com/content/article/99/105148.htm