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Doctors Divided Over Cholesterol Drugs Study

At issue: It doesn't say which medicine better at halting cardiovascular events

THURSDAY, Nov. 13, 2003 (HealthDayNews) -- A new study finds that Lipitor, the world's best-selling cholesterol drug, can halt hardening of the arteries in higher doses.

And while this research is being touted as a head-to-head comparison between Lipitor and Pravachol, a rival statin, some skeptics say this was not a true comparison at all.

Study participants who took Lipitor (atorvastatin calcium), made by Pfizer Inc., experienced a significant reduction in the progression of atherosclerosis compared to patients taking Pravachol (pravastatin), made by Bristol-Myers Squibb. Atherosclerosis slowly worsened in those taking Pravachol.

Atherosclerosis refers to a buildup of plaques in the arteries, which is a leading cause of death from heart attack and stroke.

These findings, which were presented Nov. 12 at the American Heart Association annual meeting in Orlando, Fla., are being hailed as evidence of Lipitor's superiority.

"These results clearly show that aggressively lowering cholesterol levels with atorvastatin calcium stopped the progression of atherosclerosis," the study's lead investigator, Cleveland Clinic cardiologist Dr. Steven Nissen, is quoted as saying in a Pfizer press release.

Other experts disagree with this interpretation, however.

"You cannot make that conclusion from this study," says Dr. Richard Milani, vice chairman of the department of cardiology at the Ochsner Clinic Foundation in New Orleans. "This was not a study that truly compares two different drugs."

While the study did use two drugs, the objective was not to compare the effectiveness of the two drugs, but to see what effect different cholesterol levels had on plaque volume in the arteries, say outside experts.

The trial, called the Reversing Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) study, followed 502 patients (mostly middle-aged men) with coronary heart disease. One group of patients received 80 milligrams daily of Lipitor while another group received 40 mg daily of Pravachol.

"I think it is safe to say that the doses were different specifically to have different reductions in LDL cholesterol," Milani says. "Then, by reducing LDL to different levels, what would be the impact on plaque volume?"

The average LDL ("bad") cholesterol level of patients at the beginning of the study was 150 milligrams per deciliter of blood. Accepted guidelines recommend that levels be under 100.

Those patients taking Lipitor reached an average LDL level of 79 while those taking Pravachol reached an average level of 110.

The researchers then used intravascular ultrasound, an imaging technique, to measure total plaque volume in the arteries.

Over the course of the study, 18 months, the Lipitor patients saw their plaque volume decrease by 0.4 percent, while the Pravachol patients had an average 2.7 increase.

"They were looking at two different endpoints, which is LDL reduction down to about 79 vs. the reduction down to about 110, and they used two different drugs to do that," Milani says. Plaque volume is important but not as important as reducing heart attacks or deaths, which this study did not look at. "I'm not trying to minimize the significance of plaque volume not changing," Milani says. "These are nice things, but they don't necessarily translate into outcome."

Julie Keenan, a spokeswoman for Bristol-Myers Squibb in Princeton, N.J., would not comment on the difference in doses. "While the results are informative," she says, "intravascular ultrasound technology hasn't been demonstrated to predict clinical outcomes, so additional studies would need to be conducted to see if differences would cause different reductions."

The study still leaves unanswered one of the most important questions in cardiology: How low do you go, when it comes to cholesterol?

National goals are to get LDL levels under 100. But does that mean 98 is good enough, or that you need to get to 78? "That's a question no one has the answer to," Milani says.

But we might expect the answer in March, when the results of a trial called "Prove It" are announced. That trial is, in fact, a direct head-to-head comparison of Lipitor and Pravachol using as outcomes heart attacks and deaths. But the "Prove It" trial, sponsored by Bristol-Myers Squibb, is not without its own critics, including Nissen, who told The New York Times that it was driven more by marketing than by medicine.

Milani says: "We know [the ideal LDL level] is probably below 100, but is it 65 or 95? And that's what this study ("Prove It") is designed to do. The [REVERSAL] study doesn't do that. It's important. It adds information, but it's not something that should impact what we do clinically."

Lipitor, introduced in 1997, has become the top-selling statin, with $6.5 billion in sales expected in the United States this year, according to IMS Health, which tracks such trends. Pravachol, introduced in 1991 as the second statin on the market, has $1.9 billion in sales. Pravachol loses its patent protection in 2006, while Lipitor keeps its patent until 2011.

More information

The American Heart Association has more information on cholesterol-lowering drugs and on atherosclerosis.

SOURCES: Richard Milani, M.D., vice chairman, department of cardiology, Ochsner Clinic Foundation, New Orleans; Julie Keenan, spokeswoman, Bristol-Myers Squibb, Princeton, N.J.; Pfizer, Inc. statement
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