A new blood thinner proved better than Plavix, one of the world's top-selling drugs, at preventing heart problems after procedures to open clogged arteries, doctors reported Sunday. But the new drug also raised the risk of serious bleeding.
People given the experimental drug, prasugrel, were nearly 20 percent less likely to suffer one of the problems in a combined measure -- heart attack, stroke or heart-related death -- than those given Plavix, a drug that millions of Americans take to prevent blood clots that cause these events.
However, for each heart-related death that prasugrel (PRASS-uh-grell) prevented, compared to Plavix, almost one additional bleeding death occurred.
"There is a price to pay" for greater effectiveness, Dr. Deepak Bhatt, a Cleveland Clinic cardiologist, wrote in an editorial accompanying the results, which were published online by The New England Journal of Medicine and presented at an American Heart Association conference in Florida.
Still, many doctors said that on balance, the new drug comes out ahead, and offers great promise as a more potent alternative to Plavix, which costs $4 a day and does not work for many patients.
"I'm encouraged by the results" and think prasugrel should win Food and Drug Administration approval because it so dramatically cuts non-fatal heart attacks, said the Cleveland Clinic's Dr. Steven Nissen, a frequent government adviser.
Doctors can sort out who might most benefit from it, such as diabetics, and who might face too much bleeding risk to use it, like the elderly, people who previously had strokes and those with kidney problems, he said. (The Cleveland doctors give to charity or the clinic the consulting and research fees they earn from drugmakers.)
Doctors also were waiting for prasugrel's makers to clarify why they stopped two small studies of it a week ago. They said it was due to dosing problems but did not explain.
Prasugrel is being developed by Indianapolis-based Eli Lilly and Co. and a Japanese firm, Daiichi Sankyo Co. It could be a hugely important drug, and the study has been one of the most-watched tests of a novel heart medication in recent years.
Like Plavix, prasugrel prevents blood components called platelets from sticking together and forming a clot. Anti-platelet drugs are advised for most people with stents -- tiny mesh tubes that keep arteries open after balloon angioplasty, an artery-clearing procedure that more than a million Americans have each year.
Plavix, sold by Sanofi-Aventis SA and Bristol-Myers Squibb Co., has been the most effective drug of this type. More than 70 million people have taken it since it went on sale a decade ago.
Plavix had 18.6 million prescriptions and nearly $3 billion in U.S. sales last year, according to IMS Health, a healthcare information firm. Worldwide sales were nearly $6 billion.
The study comparing it to prasugrel involved 13,608 patients from 30 countries and was led by Dr. Elliott Antman at Harvard Medical School and Brigham and Women's Hospital in Boston. Prasugrel's makers paid for the study; many of the researchers work or consult for them.
Study participants were having angioplasty due to heart attacks or blockages causing sudden or worsening chest pain, and were randomly assigned to one drug or the other for six to 15 months.
The results: about 12 percent of people taking Plavix but only 10 percent on prasugrel suffered heart attacks, strokes or heart-related deaths -- a 20 percent reduction in risk. Only 1.1 percent on the new drug developed blood clots in stents versus 2.4 percent on Plavix -- a 52 percent lower risk. Prasugrel also worked faster than Plavix and showed more effectiveness at the first checkpoint -- three days.
However, major bleeding occurred in 2.4 percent of those on prasugrel versus 1.8 percent of those on Plavix. This included brain or gastrointestinal bleeding, or after falls. Fatal bleeding was uncommon, but four times more frequent with the new drug.
Results hinted that some people might be in greater danger -- those who had a previous stroke, were elderly, or weighed less than 132 pounds.
These signs are why prasugrel's makers suspended two small studies a week ago to see whether such patients should be included in the study or should get a lower dose, said Dr. Anthony Ware of Eli Lilly.
"It was a precaution ... because of a risk of a safety problem rather than an actual one," he said.
Lilly will conduct another big study of prasugrel in people not having angioplasty but on medications because they are at risk of having a heart attack, Ware said.
That 10,000-person study will be led by Dr. E. Magnus Ohman at Duke University Medical Center.
In the study reported on Sunday, "the benefit clearly outweighs the risk" for most patients, Ohman said.
Bhatt of Cleveland Clinic noted that even aspirin -- which is widely recommended to prevent clots and was prescribed to all patients in this study -- carries a risk of bleeding.
Dr. Spencer King, a heart specialist at Piedmont Hospital in Atlanta and spokesman for the American College of Cardiology, was on the safety monitoring committee for the study. He said prasugrel would be "a little bit of a tough sell" to doctors who are comfortable with using Plavix, but that competition could give patients drugs more closely matched to their needs.
"We've had one size fits all ... now we'll have two choices," King said.
Dr. Harlan Krumholz, a Yale University cardiologist with no role in the study, noted that "in absolute numbers, for every 1,000 people you treat, you'd save a lot more heart events than you'd cause bleeds," because heart problems are more common.
Cost also keeps many people from taking Plavix now. Prasugrel's makers have not said what it would cost, but "if they start competing on price, it could be a boon for the health care system," Krumholz said.