High-Cost Cholesterol Drug Combo Shows No Benefit

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Cholesterol Drug

Vytorin, a cholesterolmedication co-marketed by Merck and Schering-Plough and among the most commonlyprescribed, is no more effective than a treatment available in generic form inthe prevention of accumulation of plaque on artery walls, according to a studyreleased on Monday by the companies, the Washington Post reports (Stein, WashingtonPost, 1/15).

The study, led by John Kastelein of the University ofAmsterdam Medical Center, involved 720 patients with a genetic disorder called heterozygousfamilial hypercholesterolemia that often prompts large increases in levels ofLDL, or bad, cholesterol (Maugh, LosAngeles Times,1/15). Participants took either Vytorin -- a combination of Zetia, which blocksabsorption of cholesterol in the intestines, and Zocor, a statin available ingeneric form -- or Zocor alone (Sternberg [1], USA Today, 1/15). The study, which lasted two years,sought to provide information about whether Vytorin could prevent theprogression of cardiovascular disease (Berenson, New York Times, 1/15).

The study found that participants who took Vytorin experienced a 58% decrease in their LDL cholesterol levels, compared with 41% for those who took Zocor (Los Angeles Times, 1/15). However, the study found no statistically significant difference in the accumulation of plaque on artery walls among participants who took Vytorin and those who took Zocor (Bloomberg/Boston Globe, 1/15).

According to the Wall Street Journal, the study has "big economic significance" because several statins are available in generic form at a cost of $1 or less per pill, compared with about $3 per pill for Vytorin (Winslow/Rubenstein, Wall Street Journal, 1/15). The companies plan to explain the results of the study in March at a meeting of the American College of Cardiology (Stark, Philadelphia Inquirer, 1/15).

Explanation of Results

Lee Davies, a spokespersonfor the joint effort of Merck and Schering-Plough, said that, because moststudy participants previously had taken statins, the detection of anyadditional benefit from Vytorin became more difficult (Sternberg [2], USA Today, 1/15). Davies said that the study "wasnever intended to be a definitive study on outcomes." In addition, bothgroups of participants "started at incredibly high LDL levels, so thepatients were not brought to goal," he said, adding, "If they were broughtto goal, they might have had different outcomes" (Bloomberg/BostonGlobe, 1/15).

Schering-Plough Chief Medical Officer Robert Spiegel said, "Of course wewould have preferred a more positive result, but in some ways the results arenot totally surprising" because of the participants involved.

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Researchers completed the study, called Enhance, in April 2006, and the"long-delayed publication of its results has drawn scrutiny in the mediaand Congress in recent weeks," according to the Journal (WallStreet Journal, 1/15). Merck spokesperson Skip Irvine said that thecompanies delayed the release of the study because of "some variability inthe imaging data that we couldn't explain" (Philadelphia Inquirer,1/15). Davies added that the companies did not delay the release of the studybecause of the negative results and that the companies have had the results foronly two weeks (New York Times, 1/15).

Congressional Response

House Energy and Commerce Committee Chair John Dingell (D-Mich.) onMonday said that the committee in December 2007 began an investigation into thedelay in the release of the study (Reichard, CQ HealthBeat, 1/14).The investigation will continue, Dingell and Rep. Bart Stupak (D-Mich.) said.

Dingell said, "Merck and Schering-Plough's delay in releasing studyresults, as well as their attempt to manipulate the data is, quite frankly,suspicious" (Wall Street Journal, 1/15). Stupak said,"In light of today's results, which were released nearly two years afterthe Enhance trial ended, it is easy to conclude that Merck and Schering-Ploughintentionally sought to delay the release of this data" (New YorkTimes, 1/15).

In addition, FDA likely will "face questions about how thedrug was approved and promoted," according to the Journal (WallStreet Journal, 1/15).

Cardiologist Comments

Steven Nissen, chair ofcardiology at the Cleveland Clinic, called the results of the study"shocking," adding, "This is as bad a result for the drug asanybody could have feared" (New York Times, 1/15). Accordingto Nissen, the study indicates that "physicians should now stop using(Zetia) or Vytorin as a primary therapy for patients with highcholesterol" (Wall Street Journal, 1/15).

Harlan Krumholz, a cardiologist at Yale University, said that the companies shouldhave released the study earlier. Krumholz said, "People may have been onthis drug without the ability to know that there was additional data that mayhave thrown into question its effectiveness. That's extremely unfortunate, andthat's an understatement" (New York Times, 1/15).

Other cardiologists said that they would continue to prescribe Vytorin topatients who experience side effects from high dosages of statins. MichaelDavidson, director of preventive cardiology at the Pritzker School of Medicine at the University of Chicago,said, "We treat based (on) goals rather than (on) specific drugs. That'sthe important message that is not changed by this trial" (WallStreet Journal, 1/15). Helene Glassberg, an assistant cardiology professorat the University of Pennsylvania, said that the study might notchange prescriptions for cholesterol medications because the "message isstill that lower is better, especially for LDL's" (Philadelphia Inquirer,1/15).

Reprintedwith permission from kaisernetwork.org. You can view the entire Kaiser Daily Health Policy Report, search the archives, and sign upfor email delivery at kaisernetwork.org/email . The Kaiser Daily Health PolicyReport is published for kaisernetwork.org, a free service of The Henry J.Kaiser Family Foundation.

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