Cardiologists looking at new generation of drugs as Plavix trial shows double dosage best for angioplasty
MONDAY, Sept. 28 (HealthDay News) -- Even as they digest the latest news on what dose of the clot-dissolving drug Plavix is best during angioplasty, cardiologists are looking at the next generation of clot-busters that could replace Plavix.
Clot-dissolving therapy was the big buzz among cardiologists at last week's Transcatheter Cardiovascular Therapeutics conference in San Francisco, according to Dr. Daniel I. Simon, a professor of cardiovascular research at Case Western Reserve University School of Medicine in Cleveland.
"What is the best dose of Plavix to be used in heart attacks?" Simon asked. "That is the number one question in cardiology."
But right behind that question is one about the role of two new antiplatelet agents -- prasugrel (Effient), which was approved by the U.S. Food and Drug Administration in July, and ticagrelor (Brilinta), which is expected to be submitted for FDA approval by the end of this year.
Trials have shown that both drugs can be more effective at keeping arteries open while reducing the risk of excess bleeding, which is the main hazard of Plavix (clopidogrel), Simon said.
"You have to balance the risk of bleeding, which is a safety issue, with efficacy, preventing heart attack and stroke," he said. "The more potent an antiplatelet agent you have, the more bleeding you might have. There are investigations that have been published showing that increasing the dose of clopidogrel can improve efficacy without more bleeding. We are trying to get to a sweet spot."
Platelets are the cells that clump together to form artery-blocking clots.
The latest of those trials, published in the Oct. 6 issue of the Journal of the American College of Cardiology, found that a 600-milligram dose of Plavix is more effective than a 300-milligram dose during angioplasty for people with the most severe form of heart attack.
The study of 3,602 people who underwent angioplasty found a 28 percent lower incidence of death and major coronary problems in those who received the higher dose.
While similar results have been reported in trials comparing 600-milligram to 300-milligram doses of Plavix in other groups of patients having angioplasty, this report is the first done in people with the most severe form of heart attack.
But "Plavix is a problematic drug," said Simon, who wrote an editorial accompanying the journal report, in part because some people are genetically resistant to its activity. And so, he said, "interventional cardiologists are confused right now about what is the most effective regimen."
Prasugrel has been shown to be superior to clopidogrel in one or more trials, and a study presented at the San Francisco meeting gave the advantage to ticagrelor in a head-to-head trial with clopidogrel.
"The biggest news was that ticagrelor reduced total mortality by an absolute 1 percent, which was a relative 19 percent reduction in mortality compared to clopidogrel," said Dr. Christopher Cannon, an attending cardiologist at Brigham and Women's Hospital in Boston, who presented the trial results at the meeting.
In addition, less bleeding was seen in people who had bypass surgery and were given ticagrelor rather than clopidogrel, he said.
One great advantage of ticagrelor is that its effects wear off in about 48 hours, compared to five days for clopidogrel, which reduces the possibility of unwanted bleeding, Cannon said.
Still, most people treated at Brigham and Women's Hospital get clopidogrel, with prasugrel reserved for cases in which excess bleeding is especially dangerous, he said.
The transition to the newer clot-dissolving drugs is complicated by the issue of cost, Simon said. A generic version of Plavix is now available in Europe and is expected to be available in the United States in a year or two. That would decrease the cost of clopidogrel therapy from the current $4 a day to $1 a day.
But another study presented at the meeting found that the overall cost of using prasugrel was about the same as that of generic clopidogrel, because the newer drug, although more expensive, reduced hospitalizations for bleeding.
"There was a 38 percent reduction in hospitalizations," Cannon said. "When you add up all the costs, you end up saving money."
Another issue about Plavix is how long its use should be continued in lower-dose form. A general practice is to continue therapy for about a year, but a recently reported study found that for people taking Plavix who required bypass surgery, stopping the medication five days before surgery reduced the incidence of excess bleeding and the length of hospitalization.
An introduction to antiplatelet agents is offered by the American Heart Association.
SOURCES: Daniel I. Simon, M.D., professor, cardiovascular research, Case Western Reserve University School of Medicine, Cleveland; Christopher Cannon, M.D., attending cardiologist, Brigham and Women's Hospital, Boston; Sept. 28, 2009, Journal of the American College of Cardiology, online; Sept. 21-25, 2009, presentation, Transcatheter Cardiovascular Therapeutics conference, San Francisco
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