Mixed Reviews for 2 of Pfizer's Top Drugs

By ALEX BERENSON

Published: March 9, 2005

Two studies presented yesterday at a cardiology conference in Orlando, Fla., offered mixed news for two Pfizer drugs, the cholesterol-lowering medicine Lipitor and the hypertension drug Norvasc.

The first study showed that a high dose of Lipitor lowers heart attacks and strokes more than a lower dose. But the high dose did not reduce overall deaths, because patients on that dose were more likely to die from cancer and other factors.

The second study showed that patients taking Norvasc were less likely to die than those on another regimen of hypertension medications, and that the Norvasc treatment appeared to raise good cholesterol. Still, the study failed in its initial goal of proving that Norvasc lowers the rate of heart attacks or fatal coronary heart disease compared with the other hypertension treatment.

Pfizer, the world's largest drug company, sponsored both studies. Shares of Pfizer, as well as the major market gauges, closed the day down. Pfizer fell 42 cents, to $26.76.

Lipitor is the world's top-selling drug, with $11 billion in sales last year, while Norvasc ranks third, with $4.5 billion in sales. The two medicines together accounted for about 30 percent of Pfizer's total sales, and an even higher share of its profit.

Last year, Pfizer introduced a single-pill combination of Lipitor and Norvasc called Caduet, although Caduet's sales have been slow so far.

Lipitor is the most widely used in a class of drugs called statins, which work by cutting the so-called bad cholesterol that can cause fatty plaques to build up in the arteries and lead to heart attacks. Norvasc lowers blood pressure, another risk factor for heart attacks.

Dr. John C. LaRosa, the lead investigator on the Lipitor study and the president of the State University of New York Downstate Medical Center in Brooklyn, said the study showed that many heart patients should take high doses of Lipitor to lower the levels of bad cholesterol in their blood as much as possible.

The study, which followed 10,000 people over five years, compared patients taking 10 milligrams of Lipitor with those taking 80 milligrams, the maximum dose. Those on the higher dose had a 22 percent lower risk of a heart attack and a 25 percent lower risk of stroke.

But the reduced risk of heart attack and stroke from the higher dose did not translate into a lower risk of death over all, because many more people died from other factors on the higher dose. Over all, 284 patients taking 80 milligrams died, compared with 282 patients taking 10 milligrams.

In an editorial in The New England Journal of Medicine that accompanied the study, Dr. Bertram Pitt, a cardiologist at the University of Michigan School of Medicine, wrote that doctors should be wary of increasing Lipitor doses. The higher death rate "is a matter of concern," Dr. Pitt wrote.

Dr. LaRosa said he believed that extra noncardiovascular deaths on high-dose Lipitor were probably a result of chance. "I am completely comfortable with the safety of the 80-milligram dose," he said.

The Norvasc study also had somewhat paradoxical results. The study, which followed almost 20,000 patients with high blood pressure from 1998 until 2004, showed that patients taking Norvasc had a 15 percent lower death rate from all causes than those taking beta blockers, a different type of blood pressure drug. Deaths from heart attacks and other cardiovascular events alone were 25 percent lower in patients taking Norvasc.

But Norvasc failed to show a statistically significant reduction in deaths from fatal coronary heart disease, the initial goal of the trial.