Controversial Cholesterol Drug Redeemed By Global Clinical Test
The wheels of drug research grind slowly, but they can grind exceedingly fine.
Merck said Monday that its cholesterol drug Vytorin was vindicated by a nine-year-long clinical study that aimed to find out if adding a drug that blocked the absorption of cholesterol to a statin, long the gold standard for cholesterol care, would help patients at a high risk of heart attack and stroke.
Previous research had raised doubts about Vytorin's effectiveness. In a bit of a surprise, the study, known by the acronym IMPROVE-IT, showed that the drug worked. Still, the effects were modest.
Researchers found that when people took Vytorin (a combination of the statin simvastatin and ezetimibe, the cholesterol blocker) for seven years, their risk of heart attack and stroke was about 2 percentage points lower than patients taking only simvastatin.
All told, 32.7 percent of patients taking Vytorin experienced a heart attack or stroke compared with 34.7 percent of those taking simvastatin alone. In relative terms, Vytorin reduced the chances of a heart attack or stroke by 6.4 percent over seven years. As for side effects, they were about the same for both groups.
"This is a reminder to everybody that all the stuff they've heard about cholesterol is true," Dr. Christopher Cannon, the principal investigator for the study, told Shots in an interview. "Lowering the cholesterol to even lower levels than we had in the past looks to be beneficial," he said.
The results were presented Monday in Chicago at a scientific meeting of the American Heart Association.
Vytorin and Zetia, which is the brand name for ezetimibe alone, have been on the market for years. In approving them, the Food and Drug Administration relied mainly on data that showed the drugs reduced bad cholesterol rather than on whether the drugs led to fewer heart attacks and strokes among people who took them.
"There's still some uncertainty, but overall it's good news," Yale cardiologist Harlan Krumholz told Shots. "It means that there's another option for treatment that has some evidence behind it."
Using a laboratory measurement, such as bad cholesterol, as a shortcut in clinical research is common.
But a previous study that looked at thickening of the arteries that carry blood to the brain raised doubts about Vytorin and Zetia. The extra drug didn't appear to reduce thickening compared with simvastatin alone. Merck, which bought Vytorin's maker Schering-Plough in 2009, agreed to pay $688 million last year to settle a suit brought by investors who claimed the companies had harmed them by withholding those unflattering data.
IMPROVE-IT looked at patients at a high risk of heart attack and stroke. Would Vytorin and Zetia help patients at lower risk? Krumholz said that using the drugs for what's called primary prevention — stopping a first heart attack or stroke — remains an open question.
Doctors and patients also don't know for sure how effective Zetia is when added to more potent statins, such as atorvastatin (the generic form of Lipitor) and Crestor.
It's unlikely that a study like this one will be extended to those other drugs.
The IMPROVE-IT trial was huge — more than 18,000 patients. And it was expensive. "The exact costs of a trial like IMPROVE-IT are difficult to calculate but are on the order of hundreds of millions of dollars," a Merck spokeswoman said in an email to Shots.
And, speaking of cost, Vytorin isn't cheap. A 30-day supply costs more than $200 at Costco. Atorvastatin, or generic Lipitor, runs $20 or less, depending on the dose.
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