Tuesday, June 19, 2007

Lipitor or simvastatin? - Lipitor is not superior

Pfizer Backtracks on Lipitor’s Edge Over Rival

Posted by Jacob Goldstein

Earlier this year, Pfizer issued a press release trumpeting an analysis that suggested the company’s cholesterol-lowering drug Lipitor helped patients more than simvastatin, a cheaper generic competitor originally sold by Merck as Zocor.

Today Pfizer filed a two-paragraph statement with the SEC explaining that those results were wrong. By the study’s primary measure of cardiovascular risks, patients who took Lipitor didn’t fare significantly better than those who took simvastatin.

That’s quite a rowback by Pfizer, which is fighting in the medical trenches to keep Lipitor sales humming. The March press release by Pfizer quoted a study author as saying the “analysis is important for physicians, employers and formulary directors at managed care companies who are making real-world treatment decisions for patients” because it “further supports the cardiovascular benefits previously seen with Lipitor.” There was no corrective press release issued today.

Generic simvastatin has been stealing market share from Lipitor since it became available last year.

The flawed study analyzed data from about 80,000 members of a managed care organization who had taken either Lipitor or simvastatin. The primary analysis compared the rate of serious cardiovascular problems, such as heart attacks and strokes, in patients who had been taking either drug for at least three months. The study found that, after adjusting for differences in doses of the medicines, the risk of cardiovascular events was 14% lower in patients who took Lipitor.

But according to the SEC filing today, “a subsequent review by the Company” found that the difference was in fact only 10% — not enough to be considered statistically significant, the standard test of scientific validity, Pfizer said.

The mistake was due to a “programming error” and came to light after the manuscript was submitted for publication in a medical journal, Pfizer spokeswoman Vanessa Aristide told the Health Blog this afternoon. Initial results from the study were presented at an American Heart Association epidemiology and prevention conference in March.

A secondary analysis included in the study looked at the difference between patients on Lipitor and simvastatin starting on the first day they took the drugs. That analysis found that Lipitor reduced cardiovascular risk by 26% more than simvastatin. The revised findings issued today said that difference was also lower than originally reported, but at 22% it was still enough to be statistically significant.

Update: We just got Pfizer senior vice president Michael Berelowitz on the phone. He explained that the mistake occurred because the initial analysis incorrectly included some data from 2005. The study was supposed to be limited to data from between 2002 and 2004.

The error was discovered while researchers were re-analyzing the data at the request of an expert who was reviewing the manuscript, which had been submitted for publication in a journal. Berelowitz declined to name the publication.

So is Lipitor superior to simvastatin or not, we asked? “We have clinical trial data and real-world data that are intriguing, and I think it should be followed up on,” said Berelowitz, citing a previous study, called IDEAL, that directly compared the two drugs. But that study also narrowly failed to show that Lipitor was superior to simvastatin in reducing heart attacks and heart-related deaths among patients who have already had heart attacks.

He wouldn’t say whether Pfizer is funding additional head-to-head studies of the two drugs. But he encouraged those who control the preferred-drug lists known as formularies to make the comparison for themselves. “People who make formulary decisions should look at their data and see how it plays out in their world.”


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