Vytorin Should be Considered a "Last Resort"Mar 31, 2008 | Parker Waichman LLP
Vytorin should only be used as a last resort because there is no evidence that the cholesterol-lowering medication provides any more benefits than cheaper statins alone. That was the conclusion reached by a panel of four prominent cardiologists after the results of the much-delayed ENHANCE study were released at the American College of Cardiology meeting over the weekend. The study looked at whether Vytorin, which is a combination of Merck & Co.'s Zocor and Schering-Plough Corp.'s Zetia, was better at reducing clogged arteries in the neck than Zocor, a statin drug, alone.
The ENHANCE study, which was funded by Merck and Schering-Plough, focused on a group of 720 patients with a rare condition predisposing them to high cholesterol. The patients were given either Vytorin, Zetia or a high dose of simvastatin, the generic form of Zocor. While both Vytorin and Zetia were found to have significantly reduced cholesterol in these patients, neither drug provided any significant benefit versus the statin drug Zocor in slowing down clogging of the arteries. Overall, the study failed to meet its primary goal, which was to show whether Vytorin was more effective than Zocor alone in preventing progression of atherosclerosis in the carotid artery, which is in the neck.
Such plaque buildup is a major risk factor for heart attacks and stroke. Many doctors had been prescribing Vytorin or Zetia on the theory that the drugs would reduce this risk in people with high cholesterol. The ENHANCE study was a serious blow to this theory.
This Sunday, the full ENHANCE study was discussed at the American College of Cardiology's annual meeting. A panel of four doctors concluded that Vytorin should be used only as a last resort, considering that the expensive drug did not provide any added benefits. "Our strongest recommendation is that people need to go back to statins," said panel member Dr. Harlan Krumhotz. "We really think there's just a small group of patients who cannot get to target (cholesterol) on statins." He said doctors should maximize the doses of statins and then try adding other drugs such as niacin-based drugs or fibrates in an attempt to lower LDL cholesterol levels as current practice guidelines recommend. The doctors said that Vytorin shouldn't be widely used until a larger study proves whether the pill reduces the risk of heart attacks and deaths, the doctors said.
That study is now underway. On Friday, researchers from Brigham and Women's Hospital in Boston and Duke University in Durham, North Carolina said the trial - known as Improve-It - will be expanded by 80 percent to ensure it has enough patients to get a clear result. The 2 1/2 year study, originally intended to include at least 10,000 patients, will now follow 18,000 patients. Doctors are looking for a 10 percent reduction in complications like heart attacks and deaths. Improve-It, uses half the dose of Zocor, sold generically as simvastatin, in both groups.
Several doctors attending the weekend conference criticized Merck and Schering-Plough for not subjecting Vytorin to a large clinical trial until Vytorin had been on the market for some time, and was very widely prescribed. The companies have also been criticized for their handling of ENHANCE. The data from the ENHANCE trial was supposed to be released by March 2007, but that didn’t happen. Last November, the doctor who supervised the ENHANCE trial told the New York Times that the drug’s makers, who controlled the study’s raw data, blocked its release. In December, a congressional committee requested more information on the ENHANCE study. Merck and Schering-Plough maintained that the ENHANCE results were delayed because of the complexity of the data.
Merck and Schering-Plough also tried at one point to change the ENHANCE study’s endpoint. The endpoint is the main medical result the study was meant to measure, and it is generally accepted among scientists that for a clinical trial to be valid, the endpoint must never change. Following a great deal of outcry, Merck and Schering-Plough backed off changing the ENHANCE endpoint in December.