The estimated 30 million Americans currently taking statin medications for cholesterol may have a new choice for lowering their levels of "bad" cholesterol in the years to come. An experimental drug was shown to have a dramatic effect on cholesterol levels, lowering the bad stuff and raising the good.
Investigators presented the trial results this morning at the American Heart Association meeting in Chicago. Research showed that the new cardiovascular medication, known as anacetrapib, more than doubles the level of good HDL cholesterol and cuts bad LDL cholesterol in half.
"My eyes popped right open when I saw the results," said Dr. Christopher P. Cannon, senior investigator of the TIMI Study Group in the cardiovascular division of Brigham and Women's Hospital and lead author of the study. "Anyone who has seen this data is more excited than they have been in 10 years for new treatments for heart disease."
Anacetrapib was being used in a trial called DEFINE -- short for Determining the Efficacy and Tolerability of CETP Inhibition with AnacEtrapib. It included more than 1,600 patients who took either anacetrapib or a placebo. As is standard procedure with new medications, it was being tested first to make sure it was safe; tests of how well it worked would come later.
But along with confirmation of the drug's safety came hints that it could be effective as well.
"The biggest effect we saw was preventing the need for bypass surgery or angioplasty," said Cannon. "This need was reduced by two-thirds in just 18 months in stable outpatients who were on a statin and treated to their current guideline goals. This told me that this mechanism might work."
Four years ago, the drug manufacturer Pfizer halted the development of a similar medication, known as torcetrapib, after phase III trials showed a link to heart attacks and early death.
Merck and Co., Pfizer's competitor, sponsored the study on the new experimental drug.
"Merck has taken a prudent course by doing a smaller study to generate some preliminary information about the drug's effect," said Dr. Harlan Krumholz, professor of medicine, epidemiology and public health at the Yale University School of Medicine. "But importantly, they are not assuming benefit based on the lab test, and are now moving to a large study to determine if the drug will help people."
The failed Pfizer trial drug seemed to cause spikes in blood pressure and changes in hormone levels. In the end, researchers thought both side effects contributed to the increased risk of death.
Cannon and his fellow investigators took those negative side effects into account when setting up the new trial.
"Thankfully, we saw that it does appear to be safe, so that we can now do a definitive study to see if this is in fact beneficial," said Cannon.
Statins have been proven to lower bad cholesterol levels and reduce overall risk of heart disease. But while they have been proven to benefit patients with bad cholesterol, statin drugs do not significantly raise HDL levels. High levels of LDL and low levels of HDL are both believed to be risk factors for heart disease.
The average study participant had HDL levels around 40, which, according to the American Heart Association, borders on low for both men and women. The study results showed that the average patient achieved levels around 100, a 138 percent increase. HDL cholesterol levels around 60 or higher give some protection against heart disease.
Dr. Steven Nissen, chairman of the department of Cardiovascular Medicine at Cleveland Clinic, said the results could mean a good strategy for raising HDL.
"Raising HDL levels has been a therapeutic target where we have not had any major success, so the fact that we're on the verge to getting HDL higher would be a major deal," said Nissen.
Exercise, cutting out unhealthy foods, drinking (some) red wine and eating (a little) dark chocolate have all been shown to contribute to natural increases in HDL levels. But Dr. Merle Myerson, director of the Cardiovascular Disease Prevention Program at St. Luke's-Roosevelt Hospital in New York, said that low HDL can still be tough to improve, with or without medication.
"Statins and niacin do raise [HDL] (and lowering very elevated Triglycerides also helps raise HDL) but many times it is 'stubborn' and we do not see much of a raise," Myerson said in an e-mail.
While the results are certainly intriguing, many doctors warn that it will be very important to watch for the results of a bigger trial to see how the drug will affect the general population.
"This study was too small and too short to definitively answer the question," said Nissen. "It's a door opening but not a final answer."
Cannon agrees, which is why a four-year, 30,000-participant, international trial led by Oxford investigators will begin early next year. Researchers will examine the effects of the drug on patients who are on a statin and have known heart disease.
Until then, Krumholz said that the medical world will have to wait to know if the promise of the current results will be fulfilled.
"[This study] has great significance for those who hope that we can introduce a new drug that will markedly reduce risk of cardiovascular disease in those for whom current strategies are inadequate," said Krumholz. "The implication for patients will have to wait until the next study."