Vytorin combines simvastatin (sold as in individual ingredient under the brand name Zocor) and ezetimibe (also known as Zetia) to reduce the production of “bad” cholesterol. An FDA review of data from clinical studies, adverse event reports, and prescription use of simvastatin indicated patients who took doses of 80 mg or more of simvastatin were at greater risk for developing a muscle injury known as myopathy. Myopathy, which causes pain, tenderness or weakness, is a known side effect of all statin drugs. Myopathy can lead to rhabdomyolysis, a more serious condition that can lead to kidney failure, which can be fatal.

Much of the data reviewed by the FDA came from the Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine (SEARCH), a clinical trial aimed to better understand the relationship between high-dose simvastatin use and muscle injury.

Vytorin also carries a risk of liver damage and liver problems such as hepatitis, cirrhosis and even liver failure. A February 2008 study also found that Vytorin was no more effective than simvastatin alone in lowering cholesterol, and that patients taking Vytorin actually had more plaque buildup than patients taking simvastatin alone.

SOURCE: Vytorin Recall › FDA warns of link between cholesterol drug, muscle injury

The SEAS study sought to test Vytorin’s effectiveness as an alternative to surgery in reducing arterial clogging caused by high cholesterol. The results, which were announced in a July 2008 press conference, did not favor the drug. Not only did researchers find that Vytorin worked no better than cheaper, generic statins, they also discovered that patients taking Vytorin experienced 50 percent more new cancer cases and cancer deaths than the subjects who took placebos.

Merck and some of the researchers connected to the SEAS study dismissed the results as a “fluke,” while many physicians and medical researchers not connected to the drug company remained skeptical and cautioned consumers to stick with traditional statins to control cholesterol levels. For instance, Merck’s Zocor, taken alone, was shown to be more effective than Vytorin and cost about one-third as much because it had become available as a generic drug.

That research promoted many municipalities that had included Vytorin in their health plans to file lawsuits against Merck, essentially asking for their money back. Vytorin and its sister drug Zetia, made by Schering-Plough, brought in sales of more than $5 billion at their peak. The sales have fallen but continue to earn $4 billion annually.

Vytorin is a hybrid drug which combines Merck’s Zocor with Schering-Plough’s Zetia to combat both dietary and hereditary cholesterol. The FDA said that ample evidence exists showing Zocor to be safe, but insufficient evidence exists on Zetia to “rule out a cancer risk at this time.”

Two additional Vytorin studies known by the acronyms SHARP and IMPROVE-IT are ongoing and scheduled to end in 2010 and 2012.

SOURCE: Vytorin Recall › FDA says it finds no Vytorin-cancer link, but unsure

Merck

The Enhance study revealed that the pairing of Schering-Plough’s Zetia and Merck’s Zocor, which constitutes Vytorin, to be no more effective and possibly even less effective than Zocor alone or other much cheaper, generic statins in treating arterial plaque.

But more than the disappointing results, there was the delay in making this information public. Results of the Enhance trial were completed in April 2006 but were not released until January 2008, after mounting pressure and suspicion over the delay.

Many plaintiffs, including a number of municipalities, sued Merck and Schering-Plough upon discovering that the drug makers knew the results of the Enhance trial but withheld them from the public for up to 2 years. The trial revealed Vytorin to be no more effective than cheaper generic statins in controlling cholesterol.

Nevertheless, the drug makers forged ahead with aggressive marketing campaigns for Vytorin, earning billions while allegedly knowing about the drug’s shortcomings.

Last month, Merck and Schering agreed to settle with attorneys general from 35 states who claimed the drug makers improperly marketed Vytorin and Zetia. Merck agreed to pay the states $5.4 million for costs accrued in investigating the potential violations of consumer-protection laws.

The settlement announced this week resolves all of the lawsuits seeking class-action status that were filed in New Jersey federal courts by consumers who bought and used Vytorin or Zetia. Many of the complaints sought compensation for personal injury caused by the drugs. The SEAS trial uncovered a possible link between Vytorin and higher cancer risks.

Lawsuits against the companies over securities law violations are still pending, as is the U.S. Department of Justice’s investigation into whether the drug makers’ marketing tactics led to false claims being submitted to federal healthcare programs. Moreover, congressional committees continue to inquire about the companies’ handling of the Enhance trial.

SOURCE: Vytorin Recall › Merck and Schering pay $41.5 million to settle NJ lawsuits

Dr. Scannell said the drug made her list as a result of two studies that revealed Vytorin, which is a combination of simvastatin (Zocor) and ezetimibe (Zetia), did not reduce artery-clogging plaque buildup, although tests showed it reduced “bad” cholesterol levels.

However, she said Vytorin’s bad year wasn’t all bad for consumers, as research from the study revealed a fundamental benefit of statin drugs to people with normal cholesteral but high indicators of inflammation. She says the Vytorin failure also brought to light “the importance of knowing how new drugs actually affect the people who take them – not just their blood tests.”

Dr. Kate Scannell is an East Bay physician and syndicated columnist.

SOURCE: Vytorin Recall › Vytorin No. 3 on list of Top 10 medical stories of 2008

Think of it as a device that scrubs the blood clean, much like kidney dialysis, except that the machine targets and removes bad LDL cholesterol instead of the impurities removed by dialysis.

The cholesterol machine draws the patient’s blood from one arm. It then breaks the blood down into red blood cells and plasma, sending the red cells back into the patient’s bloodstream. Meanwhile, the machine infuses the blood plasma with the blood thinning drug heparin, which binds to the LDL cholesterol, thereby drawing it out of the plasma. The device then sends the clean plasma back into the patient’s other arm.

The machine removes and cleans 2.5 liters of blood, about half of the body’s blood supply.

This two-hour process is short lived, so it must be repeated every two weeks for effective treatment of high cholesterol. The therapy is also extremely expensive, costing about $3,000 for each session ($6,000 per month), and as such is currently used only as a last resort for patients who have been unable to lower their cholesterol after six months of diet, exercise, and pharmaceutical medicines.

Some people rack up their cholesterol score from the foods they eat. For others, too much bad LDL cholesterol is produced by the liver, thanks to the family genes. For many, elevated cholesterol comes from both sources.

To combat the cholesterol problem on both fronts, Merck teamed up with Schering-Plough to create Vytorin, a drug that combines Merck’s Zocor with Schering-Plough’s Zetia. However, clinical trials revealed that the drug was at best a flop and at most a toxic cancer-promoting drug. In either case, it failed to treat cholesterol any more effectively than cheaper generic statins.

There’s a good chance that most patients who qualify for treatment on the LDL apheresis machine have tried Vytorin first but found it to be ineffective in controlling their levels of LDL cholesterol. Familial hypercholesterolemia, a genetic predisposition for high cholesterol, occurs in approximately 1 in 500 people.

Sources include: http://www.liposorber.com/ldl/index.htm, and http://www.stltoday.com

SOURCE: Vytorin Recall › Lowering LDL by machine vs. Vytorin and Zetia

Most analysts expected the market for Vytorin to bottom out over the summer after the SEAS results became public — an event that many felt would deal the already wounded Vytorin a coup de grace. Not so, however. Vytorin refuses to assume its place on the list of has-beens with grace. Instead, it continues to stumble, choke, and flail.

The latest monthly data for Schering-Plough shows that Vytorin prescriptions continue to decline. Prescriptions for Vytorin were down 3.7 percent in September, and the drug’s share of the cholesterol market dropped from 6.4% to 6% in August. Before the SEAS and Enhance trials, Vytorin took about 8 percent of the total cholesterol market.

At the same time, prescriptions for Zetia, Schering-Plough’s half of the dualistic Vytorin, dropped 1.5% in September. Merck’s Zocor comprises the other part of Vytorin. Together, Schering-Plough and Merck shared 15.2% of the cholesterol management market last January. By June their share had fallen to 12.1 percent. Last month, the share dropped further to 10.8 percent.

Since Vytorin failed to meet it primary endpoint in the SEAS trial, was shown to be no more effective than cheaper generic statins, and has been linked to increased cancer risks, it makes you wonder why it’s being prescribed at all.

SOURCE: Vytorin Recall › Vytorin loses market strength … again

New Haven City Hall spent more than $400,000 on Vytorin and Zetia (ezetimibe) prescriptions for members of the city’s healthcare plan when it could have spent a fraction of that amount for cheaper generic statins that have proven to be as or more effective and less risky.

Zetia is Merck’s anti-cholesterol drug that works by blocking absorption of cholesterol in the digestive tract. It is combined with Schering-Plough’s statin drug Zocor, which targets cholesterol produced by the liver, to form Vytorin – a drug that works to diminish cholesterol on both hereditary and dietary fronts. Studies have shown, however, that cheaper generic statins are in some cases more effective and safer than the Vytorin cocktail.

“This drug doesn’t work. Period. It just doesn’t work,” Steven Nissen, head of cardiology at the Cleveland Clinic, told Forbes magazine.

Merck and Schering-Plough are under Congressional inquiry for possibly withholding study data that indicated Vytorin was a flop while collecting billions in sales from the drug. The companies collected windfall profits knowing that cheaper and possibly more effective drugs were on the market.

Growing controversy over Vytorin’s performance and the way its makers have handled both past and ongoing studies have spawned a number of class action lawsuits. New Haven wasn’t able to find a suit that it could join, so it’s striking out on its own.

SOURCE: Vytorin Recall › New Haven wants to recover Vytorin money

To be completely fair, pharmaceutical companies continually develop vaccines and medicines that improve the quality of life for millions of people throughout the world. Many modern pharmaceuticals also extend and save lives. In the western world, we can’t imagine life without these modern medicines.

However, events surrounding the drug Vytorin have cast into doubt the intentions – and the integrity – of pharmaceutical giants Merck and Schering-Plough. As marketing expert Rob Frankel recently told Advertising Age magazine, “The pharmas are in big trouble in terms of credibility. They’re just above congress and used-car salesmen.”

Why?

First there is the ENHANCE study that revealed the pairing of Zetia and Zocor to be no more effective than Zocor alone in treating arterial plaque. But more than the disappointing results, there was the delay in making this information public. Results of the ENHANCE trial were completed in April 2006 but were not released until January 2008, after mounting pressure and suspicion over the delay.

On May 1, 2007, before the ENHANCE results were made public, Schering-Plough’s president Carrie Smith Cox, dumped 900,000 shares of company stock, worth an estimated $28 million. The sale prompted Congress to investigate the upper realms of Schering-Plough for concrete evidence of insider trading.

While ENHANCE data were being withheld, Merck and Schering-Plough continued to heavily advertise Vytorin, spending hundreds of millions on the famous commercials featuring the aunt who looks like a pot roast. The companies knew the results of the study, yet their aggressive marketing raked in $3-5 billion per year since Vytorin’s appearance on the market. Meanwhile, patients continually overpaid for a drug that didn’t do what the ads claimed it would do.

Congress again stepped in to demand answers as to why consumers, including the federal government, had been fleeced for so long. Senator Chuck Grassley of Iowa sent a letter to the top of both companies in which he stated, “I have an obligation to the more than 80 million Americans who receive health care coverage under Medicare and Medicaid to ensure that taxpayer and beneficiary dollars are spent in a fiscally sound manner.” In the same letter, he also pointed out that at, “… a Wal-Mart pharmacy in Iowa City, generic simvastatin costs $54.54 for a month’s supply. On the other hand, Vytorin costs $112.46–more than twice as much.”

The federal government is also investigating why the ENHANCE test results released by Merck and Schering-Plough differ from the information released by those who conducted the study. A letter from the U.S. House of Representatives Committee on Energy and Commerce to Fred Hassan (Schering-Plough) and Richard T. Clark (Merck) states, “The ENHANCE trial was completed in 2006, and yet no data from the trial have been published or presented in their entirety. In fact, it appears that the study itself was not registered with ClinicalTrials.gov until October 31, 2007, a full 18 months after completion of the study. In addition, the endpoint indicated in the ClinicalTrials.gov web site appears to differ from the endpoint described in the initial study design.”

Representative Bart Stupak , D-Mich, told CBS’s Early Show “There’s certainly major misrepresentations not only to the effectiveness of the drug, but manipulating of the scientific data to further promote a product that isn’t doing what it was designed to do.”

With all of the controversy surrounding Vytorin, it would seem that Schering-Plough has sought to earn more mistrust every day and that Merck intentionally put profits before people.

SOURCE: Vytorin Recall › Vytorin scandals evoke mistrust

Merck and Schering-Plough teamed up to create Vytorin, a new cholesterol-fighting drug that combined the power of statins with Zetia, a drug that reduces absorption of cholesterol in the intestine. In this way, the battle against cholesterol would occur on both genetic and dietary fronts.

Data from the ENHANCE study, however, revealed that Vytorin was largely a flop. While it lowered LDL cholesterol, it did nothing to actually reduce plaque in the carotid arteries as promised.

Dr. Harlan Krumholz, a Yale University cardiologist, told the Associated Press that “people need to turn back to statins. We know that statins are good drugs. We know they reduce risks.”

Dr. Roger Blumenthal, a Johns Hopkins University cardiologist and spokesman for the American Heart Association, likewise advised against prescribing Vytorin, at least as the first line of treatment. “A lot of us thought that there would be some glimmer of benefit,” he told the AP, adding that doctors should first prescribe more traditional, proven cholesterol lowering drugs before turning to Vytorin.

Dr. John Kastelein, a Dutch scientist and the primary investigator for the ENHANCE trial, sounded the harshest criticism. The AP report quotes him as saying that Vytorin showed “no result . Zilch. In no subgroup, in no segment, was there any added benefit” in patients seeking to reduce plaque buildup.

Studies of Vytorin continue. IMPROVE-IT, an ongoing trial slated to end in 2012, will compare and measure the primary effects of Vytorin and simvastatin alone in approximately 18,000 patients with acute coronary syndrome. Another trial, SHARP is monitoring the results of Vytorin and placebo in kidney patients.

SOURCE: Vytorin Recall › Doctors say stay with statins