Aug. 30 (Bloomberg) -- AstraZeneca Plc’s experimental blood-thinner Brilinta prevented 16 percent more heart attacks, strokes and deaths than standard therapy with Sanofi-Aventis SA’s and Bristol-Myers Squibb Co.’s Plavix in a study.

Brilinta’s potency didn’t cause more episodes of serious bleeding, a common complication seen with drugs that ward off heart conditions by preventing blood clots from developing, the research showed. The findings position Brilinta to rival Plavix, the second-biggest selling medicine in the world with almost $10 billion in annual revenue, for millions of patients suffering from heart attacks or severe chest pain.

About 1.3 million Americans are hospitalized each year with heart attacks and chest pain known as acute coronary syndromes. While aspirin and Plavix have lowered their subsequent health risks, cardiovascular disease remains the leading cause of death worldwide. Death from any cause was also significantly lower in patients taking Brilinta, according to the results of the study known as Plato.

“I think this will become the new standard of care,” said Douglas Weaver, a cardiologist at Henry Ford Hospital in Detroit and a past president of the American College of Cardiology, in an interview. “It’s more rapid, more effective and it appears to be safer” than Plavix and another competitor, Effient, from Eli Lilly & Co. of Indianapolis and Daiichi Sankyo Co. of Japan. “I don’t think they could have done much better than they did in this trial.”

Cardiology Meeting

The trial, funded by London-based AstraZeneca, included 18,624 patients and was one of the most eagerly anticipated findings presented at the European Society of Cardiology meeting in Barcelona this week. It was simultaneously published in the New England Journal of Medicine.

“Bristol-Myers Squibb and Sanofi-Aventis have not had an opportunity to fully analyze the results of Plato,” Laura Hortas, a spokeswoman for New York-based Bristol-Myers, said in an e-mail. Plavix is approved for use in a broad group of patients with cardiovascular conditions, while the Brilinta trial focused only on patients who suffer from acute coronary syndromes including heart attacks and chest pain, Hortas said.

The results were better than investors expected, with an unanticipated 22 percent reduction in the overall risk of death and a reassuring safety profile, said Michael Leacock, an analyst at Royal Bank of Scotland in London. The consensus estimate for Brilinta sales is currently $992 million by 2014, and that is likely to rise based on the findings, he said.

Generic Competition

AstraZeneca needs Brilinta to help replace sales lost to generic competition for its best-selling drugs, as products including Seroquel that now account for about 62 percent of the company’s revenue will face lower-priced competition by 2014. Brilinta will be competing against Plavix, which is set to lose patent protection in 2011.

AstraZeneca plans to file for approval of Brilinta in the fourth quarter and aims to begin selling it next year, said Gunnar Olsson, the company’s head of cardiovascular therapy.

Brilinta, Plavix and Effient all work by preventing platelets from clumping together in the blood to form clots. Plavix and Effient, which was approved this year in Europe and the U.S., last for the life of the platelet, or about a week, and are given once a day. Brilinta needs to be taken twice daily. About 30 percent of patients don’t respond well to Plavix. Brilinta’s effects wear off in a few days, making surgery easier for patients who need it.

‘Huge Conundrum’

One in 10 patients rushed to the hospital with chest pain or heart attacks actually need by-pass surgery, said Christopher Cannon, a cardiologist at Brigham and Women’s Hospital in Boston. If they are given Plavix or Effient, they must wait five days before getting the surgery, he said.

“It’s a huge conundrum, a headache for doctors, hospitals and patients,” he said in a telephone interview. “This opens the door. It’s a neat differentiating factor that could open up treatment options.”

In the study, 9.8 percent of patients taking Brilinta for a year after being treated for a heart attack or worsening chest pain suffered another heart attack or stroke, or died from vascular disease, compared with 11.7 percent of those given Plavix. Overall, 4.5 percent of Brilinta patients died from any cause, significantly fewer than the 5.9 percent of Plavix patients who died.

Major Bleeding

The rates of major bleeding were similar between the two groups, occurring in 11.6 percent of those on Brilinta and 11.2 percent of those on Plavix. Fatal bleeding in the brain was more frequent in those given Brilinta, while fatal bleeding in other areas was more common with Plavix. Brilinta was linked to more serious bleeding in the brain and stomach of patients who didn’t undergo bypass surgery, the study found.

In an accompanying comment in the New England Journal, Albert Schoemig of the German Heart Centre in Munich wrote that the safety of Brilinta, also known as ticagrelor, needs to be tracked closely.

“The whole story concerning the adverse effects of ticagrelor may require evaluation in a much larger number of patients, something that may be beyond the capacity of a randomized trial,” Schoemig wrote. “We should carefully monitor patients receiving this drug to establish the overall impact of its side effects.”

Plavix Results

A separate study unexpectedly found high doses of Plavix and aspirin failed to reduce the risk of heart attack, stroke or death from cardiac causes better than lower doses. The trial, dubbed Current Oasis 7, involved more than 25,000 patients and is one of the first to specifically compare the most widely used doses of the two drugs given to almost all patients with heart attacks and severe chest pain.

About half of patients get the higher double dose of Plavix with the expectation that more medicine will better prevent deadly clots from forming, Cannon said. The same rationale is given for using more aspirin.

“We’ve adopted this because it makes good sense, but there is very little evidence,” he said. “It’s a fascinating thing how hard it is to prove the right dose. Now, 10 years in, we’re seeing if a higher dose helps.”

In patients who underwent procedures to clear clogged heart arteries, about 70 percent of those in the trial, the double 600-milligram dose of Plavix lowered heart risks by 15 percent. In them, 3.9 percent of those getting high dose Plavix for a week developed complications or died within a month, versus with 4.5 percent of those given the approved 300-milligram dose.

View of Effient

The trial was funded by Paris-based Sanofi and Bristol- Myers. It could change the way doctors view Lilly and Daiichi’s Effient, since studies used to get approval of the drug known chemically as prasugrel used the lower Plavix dose for comparison.

The higher dose Plavix slashed the risk of stent thrombosis, a deadly complication that occurs when a blood clot clogs a device used to prop open the artery, by 42 percent, said Shamir Mehta, director of interventional cardiology at McMaster University in Hamilton, Canada. There were no differences in stroke and death rates from cardiovascular disease alone, or in bleeding rates, he said.

“This will result in a change in practice so patients will be receiving a double dose of clopidogrel for a full week, rather than just when they first come in,” he said in a telephone interview, using the chemical name for Plavix. “All things considered, a double dose of clopidogrel looks pretty good. It comes down to safety, since the efficacy outcomes were very similar to each other.”

To contact the reporter on this story: Michelle Fay Cortez in London at mcortez@bloomberg.net

Last Updated: August 30, 2009 08:57 EDT