Joined: 17 Jul 2006
|Posted: Thu Aug 10, 2006 5:16 am Post subject: Lipitor - Limited Benefit for Stroke
Limited Benefit for Stroke
In Pfizer Study, Popular Drug
Slightly Cut Recurrence Risk;
Concern Over Hemorrhages
By THOMAS M. BURTON
August 10, 2006; Page D1
A new study sponsored by Pfizer Inc. found that the company's best-selling cholesterol drug, Lipitor, had only modest success in lowering the stroke rate in people with prior strokes, while raising red flags concerning a higher incidence of potentially devastating brain hemorrhages.
Pfizer has been trying to expand the uses for the blockbuster Lipitor as it faces increased competition from generic Zocor, which like Lipitor is a "statin" drug that lowers bad cholesterol. Currently, in addition to its use in curbing heart disease, Lipitor is approved for stroke prevention in people who have, or are at high risk for, coronary disease.
The company has hoped this latest research, published in the New England Journal of Medicine, would lead to broader use of Lipitor as a stroke inhibitor for all patients with prior attacks. But the lackluster findings suggest the company could find that difficult.
Among 4,731 patients who had had a prior stroke:
• 11.2% of the total Lipitor group suffered another stroke over five years
• 13.1% of those getting placebo pills suffered additional strokes
• In the Lipitor group, 55 of the strokes were hemorrhagic
• In the placebo group, 33 strokes were hemorrhagic
Source: The New England Journal of Medicine
The study looked at 4,731 people who had no known cardiac problems but had experienced at least one stroke within the prior one to six months. The subjects included people who had either a hemorrhagic stroke (also called a brain hemorrhage), ischemic stroke (generally caused by a blood clot) or a mini stroke.
Among the patients who took Lipitor, 265 patients, or 11.2% of the total Lipitor group, suffered another stroke over five years. That compared with 311 patients, or 13.1%, of those getting placebo pills who suffered additional strokes.
The absolute reduction in the Lipitor group, which amounted to about two percentage points, was termed "fairly modest" by Jonathan L. Halperin, director of clinical cardiology at Mount Sinai Medical Center in New York. Dr. Halperin, who wasn't connected with the study, did note that this is "the first hard evidence" that statins such as Lipitor can reduce strokes in people with previous strokes and no known coronary disease.
But the strokes that occurred in Lipitor patients included 55 hemorrhagic strokes, which can be particularly devastating, compared with 33 such events among patients getting a placebo. Researchers didn't explain whether the brain hemorrhages occurred primarily in people who had had previous brain hemorrhages, leaving open the question of whether the patients' histories, or the drug itself, may have been the primary factor.
Rochelle L. Chaiken, Pfizer's world-wide medical director/cardiovascular, says that "the benefit is clearly there" in terms of stroke reduction in people with previous strokes, adding: "We're very excited about the data. This is a population that's never been studied before." Regarding the increase in hemorrhagic stroke, Dr. Chaiken says, "The data are quite small."
Hemorrhagic strokes are rarer than ischemic attacks, accounting for less than 20% of the 700,000 strokes each year in the U.S. But they are of particular concern because they carry a much higher risk of long-term disability, including paralysis -- especially in people who are on blood-thinning medicines such as Coumadin. The article didn't describe the extent of disability among people who had hemorrhagic strokes.
"Hemorrhagic strokes are not only more fatal, but are much more disabling," says cardiologist Eric J. Topol of Case Western Reserve University in Ohio. Dr. Topol, who wasn't involved in the Lipitor study, noted that because the study compared Lipitor against placebo pills and not against another statin drug, it should have been a fairly easy comparison. "They did eke out a benefit, but it should have been overpowering."
One of the study's co-authors, Justin A. Zivin of the University of California, San Diego, said: "The [beneficial] effect is about what you get from aspirin. It's not dramatic or earth-shaking."
The research is very important for Lipitor, which with $12 billion in sales was the world's best-selling drug in 2005. Despite its huge sales, Lipitor is threatened by, among other factors, the recent introduction of generic Zocor, a competing statin also called simvastatin.
So far, the primary uses of Lipitor have been in heart patients or those at high heart risk. But strokes are more complicated than heart attacks, so it wasn't obvious that Lipitor would succeed as a stroke inhibitor for people without cardiac disease. Unlike heart attacks, which involve a piece of clot lodged into fatty plaque in coronary arteries, strokes have myriad causes, including clots that are thrown off in the heart and lodge in vessels in the brain.
The research looked at stroke patients who had LDL, or "bad," cholesterol at relatively high levels from 100 to 190 and didn't have any known previous heart disease. Among the other findings, Lipitor patients had fewer overall cardiovascular events, by 3.5 percentage points.
Dr. Topol noted that the study employed a high dose of Lipitor and that the highest dose is more likely to elicit side effects. In the end, he says, the research "may increase the use of statins, but it may not be this statin at this particular dose."
Meanwhile, the financial ties of the 11 study co-authors to Pfizer raised questions about their impartiality. The study was funded by Pfizer, and every one of the researchers had connections to Pfizer and other drug companies, ranging from research grants, to consultancies, to being Pfizer employees with stock ownership. In addition, even the doctor selected by the New England Journal of Medicine to write an opinion piece on the study also has gotten grant support from Pfizer.
Some co-authors said they were nevertheless able to make independent judgments.