High-Cost Cholesterol Drug Combo Shows No Benefit Over Lower-Cost Generic Statin, According to Drug Makers

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

The study, led by John Kastelein of the University of Amsterdam Medical Center, involved 720 patients with a genetic disorder called heterozygous familial hypercholesterolemia that often prompts large increases in levels of LDL, or bad, cholesterol (Maugh, Los Angeles Times, 1/15). Participants took either Vytorin -- a combination of Zetia, which blocks absorption of cholesterol in the intestines, and Zocor, a statin available in generic 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 the progression 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 spokesperson for the joint effort of Merck and Schering-Plough, said that, because most study participants previously had taken statins, the detection of any additional benefit from Vytorin became more difficult (Sternberg [2], USA Today, 1/15). Davies said that the study "was never intended to be a definitive study on outcomes." In addition, both groups of participants "started at incredibly high LDL levels, so the patients were not brought to goal," he said, adding, "If they were brought to goal, they might have had different outcomes" (Bloomberg/Boston Globe, 1/15).

Schering-Plough Chief Medical Officer Robert Spiegel said, "Of course we would have preferred a more positive result, but in some ways the results are not totally surprising" because of the participants involved.

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

Congressional Response
House Energy and Commerce Committee Chair John Dingell (D-Mich.) on Monday said that the committee in December 2007 began an investigation into the delay 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 study results, 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 after the Enhance trial ended, it is easy to conclude that Merck and Schering-Plough intentionally sought to delay the release of this data" (New York Times, 1/15).

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

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

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

Other cardiologists said that they would continue to prescribe Vytorin to patients who experience side effects from high dosages of statins. Michael Davidson, 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's the important message that is not changed by this trial" (Wall Street Journal, 1/15). Helene Glassberg, an assistant cardiology professor at the University of Pennsylvania, said that the study might not change prescriptions for cholesterol medications because the "message is still that lower is better, especially for LDL's" (Philadelphia Inquirer, 1/15).

Broadcast Coverage
Three broadcast programs on Monday reported on the study. Summaries appear below.

• ABC's "World News": The segment includes comments from Nissen (McKenzie, "World News," ABC, 1/14). Video of the segment is available online.
  
  
• CBS' "Evening News": The segment includes comments from Christopher Cannon, a cardiologist at Brigham and Women's Hospital, and Nissen (Couric, "Evening News," CBS, 1/14). Video of the segment and expanded CBS News coverage are available online.
  
  
• NBC's "Nightly News": The segment includes comments from Nissen and Sidney Wolfe, director of the Health Research Group at Public Citizen (Costello, "Nightly News," NBC, 1/14). Video of the segment is available online.