Two new blood thinners are better at preventing clots, heart attacks, strokes and death than two widely used drugs, Plavix and warfarin, researchers reported today at the European Society of Cardiology Congress in Barcelona, Spain. One of the drugs, Brilinta, joins the recently approved Effient in attacking the market for Plavix, which is the second-best-selling drug in the world, with annual sales of nearly $9 billion.
Brilinta, whose generic name is ticagrelor, is targeted at acute coronary syndrome, which hospitalizes an estimated 1.3 million Americans every year -- a market dominated by Plavix, known generically as clopidogrel. Acute coronary syndrome, also known as ACS, includes a broad range of problems, including unstable angina -- which is marked by acute chest pain -- and heart attack. Like other anti-clotting drugs, the new drug could also be used to prevent further blood clots in patients who undergo coronary artery bypass surgery or angioplasty to clear blocked arteries.
Dr. Lars Wallentin of the Uppsala Clinical Research Center in Sweden and his colleagues studied 18,624 patients who showed up at hospitals with ACS. Half received Plavix immediately to limit clotting and half received Brilinta. They reported at the meeting and online in the New England Journal of Medicine that 9.8% of patients receiving Brilinta for a year after the initial episode suffered another heart attack or stroke or died from cardiovascular disease, compared with 11.7% of those given Plavix -- a 16% reduction. Overall, 4.5% of Brilinta patients died from any cause in the following year, compared with 5.9% of Plavix patients -- a 22% reduction. There was no increase in the risk of dangerous bleeding associated with the new drug.
"I think this will become the new standard of care," said Dr. Douglas Weaver, a cardiologist at Henry Ford Hospital in Detroit and a former president of the American College of Cardiology. "It's more rapid, more effective and appears to be safer," he told Bloomberg News.
Like Plavix and Effient (known generically as prasugrel), Brilinta acts by preventing blood platelets from clumping together to form clots. One advantage it has is that its effects disappear within a couple of days; the other drugs last a week or so. That means patients given Plavix or Effient when they arrive at a hospital with heart problems usually must wait five or six days for surgery to give the drugs time to wear off. Brilinta patients can undergo surgery sooner.
A disadvantage of the new drug is that it must be taken twice a day, compared with once daily for the others. That is a potential problem because many patients stop taking the drug when they feel fine, even though there is a high risk of clots if they do so. As many as 1 in every 6 patients taking the drug also experienced shortness of breath, about twice the proportion among those taking Plavix. Price may also be a problem. The patent on Plavix will expire in 2011 and its price is likely to be reduced sharply as generics appear. Physicians may feel pressure from insurance companies to precribe it because of its lower cost, despite the increased effectiveness of Brilinta.
The new study was sponsored by AstraZeneca, Brilinta's manufacturer. The company hopes to have approval from the Food and Drug Administration by the end of the year and to begin selling the drug in 2010.
Warfarin, a 50-year-old blood thinner derived from rat poison, is used to treat most of the 2.3 million Americans with atrial fibrillation, a condition in which the heart beats erratically. The irregular heartbeats increase the likelihood of clotting and stroke, so anticoagulants -- primarily warfarin -- are used to reduce the risk. Warfarin, which is probably best known as Coumadin, blocks the synthesis of factors that are necessary for the blood to clot, but blood levels must be carefully regulated to prevent overdose and it interacts with some common foods, such as broccoli and spinach.
Dr. Michael Ezekowitz of the Lankenau Institute for Medical Research and Heart Center in Wynnewood, Pa., and his colleagues studied 18,111 patients with atrial fibrillation, comparing two different doses of a new drug, Pradaxa, with warfarin. They reported at the meeting and also online in the New England Journal of Medicine that the lower dose of Pradaxa was comparable to warfarin, but that patients receiving the higher dose had a 34% reduction in strokes. They were also less likely to suffer major bleeding episodes.
"From my perspective, it is an amazing result," Ezekowitz said. The highest dose "was unequivocally superior to warfarin without compromising, without major bleeding."
One big advantage of the drug is that it does not require the close monitoring of blood levels that is necessary with warfarin and there is no interaction with foods. Such monitoring can add as much as $500 per month to the relatively small cost of the drug itself. One disadvantage is that there was a small but statistically significant increase in heart attacks in the group receiving the highest dose of the drug, which is known generically as dabigatran.
The research was funded by the drug's maker, Boehringer Ingelheim of Germany, which already markets it in 40 countries. The researchers have also received funding from the company.
-- Thomas H. Maugh II