A double dose of popular anti-clotting drug Plavix failed to meet researchers' primary goal of preventing more heart attacks, deaths and strokes than the standard dose -- and it increased the risk of bleeding -- in a large new study of heart patients.

But the 25,000-patient trial did show that within a subgroup of patients -- those undergoing a common artery-opening procedure -- the higher Plavix dose was able to prevent more heart attacks and certain procedure complications than the standard dose. Using a different measure of bleeding, there also was no significant difference between high- and standard-dose Plavix, a blockbuster drug co-marketed by Bristol-Myers Squibb Co. (BMY) and Sanofi-Aventis (SNY), which funded the new study.

Although the study missed its primary goal, the positive subgroup finding could support use of the higher Plavix dose. That could help mitigate the competitive threat to Plavix posed by a new anti-clotting drug, Effient, from Eli Lilly & Co. (LLY) and Daiichi Sankyo Co. (4568.TO). A previous clinical trial showed Effient to be superior to standard-dose Plavix, but with an increased risk of major bleeding.

Still, some doctors might view Effient as a good alternative due to concerns that genetic variants in some patients, and use of heartburn drugs, can reduce the effectiveness of Plavix.

With $8.6 billion in global sales in 2008, Plavix is the No. 2 prescription drug in global sales behind Pfizer Inc.'s (PFE) Lipitor cholesterol drug, according to drug-data provider IMS Health.

Results of the new Plavix study, conducted in nearly 40 countries and titled "Current-Oasis 7," are to be presented Sunday at the annual meeting of the European Society of Cardiology in Barcelona, Spain.

Plavix was tested in people with chest pain or symptoms of heart attack who were candidates for an artery-opening procedure in which tiny devices called stents are sometimes inserted. The patients were randomly assigned to receive various dose-level combinations of Plavix and aspirin. The high dose of Plavix was given for seven days. Not all patients ended up getting the artery-opening procedure.

At 30 days after start of treatment, the combined rates of cardiovascular death, heart attack and stroke occurred in approximately 4.4% of patients on standard-dose Plavix, versus 4.2% for the double dose, a statistically insignificant difference, said Shamir Mehta, professor of medicine at McMaster University in Ontario and lead author of the study.

The risk of major bleeding as defined in the study's design increased to 2.5% of high-dose Plavix users from 2% in standard dose. Mehta said the increase was driven largely by bleeding events requiring blood transfusions. Using a different definition of major bleeding, there was no significant difference between the groups, he said.

About 70% of the study's population underwent artery procedures. Of these, the combined rate of cardiovascular death, heart attack and stroke was reduced to about 3.9% for high-dose Plavix versus 4.5% for standard dose, Mehta said. The rate of blood clots that can occur in stent recipients, also known as stent thrombosis, was reduced to 0.7% among high-dose users from 1.2% for standard dose.

The benefit of doubling up on Plavix, however, was muted in the 30% of the study's population who didn't undergo the artery-opening procedure. There was no significant difference in efficacy rates between high- and standard-dose Plavix users among these patients.

The same study found no significant differences in efficacy or safety between a high dose of aspirin and a lower dose.

Many doctors already use a higher initial dose of Plavix. Mehta thinks the study's findings will reinforce this practice. And because the double dose was only used for seven days, he said, "it's negligible in terms of cost implications." Plavix costs about $4.60 per tablet, and Effient is about $5.45 per pill; prices may vary by retailer or health plan.

Some doctors still may opt for Effient in certain patients, including those with a high risk of stent thrombosis and low risk of bleeding. Magnus Ohman, a professor of medicine at Duke University who is involved in an ongoing study of Effient, said "the purists will say [the Plavix] trial didn't meet its endpoint and it had a signal on bleeding." But he said the downsides appeared to be overcome in patients undergoing the artery procedure.

-By Peter Loftus; Dow Jones Newswires; 215-656-8289; peter.loftus@dowjones.com