Nov. 11 (Bloomberg) -- Heart stent patients taking Bristol- Myers Squibb Co. and Sanofi-Aventis SA's anti-clotting drug Plavix increased their risk of heart attacks and strokes if they also took anti-ulcer medicines like AstraZeneca Plc's Nexium.

Doctors implant about 2 million stents worldwide annually and routinely prescribe them with blood thinners such as Plavix to avoid clots. The drugs, though, raise the risk of stomach bleeding, so Nexium or one of its rivals from a family of drugs known as proton pump inhibitors is also prescribed.

About a third of patients who received a heart stent and Plavix suffered complications within a year when they also took the ulcer medicines, according to a study reported today at an American Heart Association conference in New Orleans. The finding may change medical practice, the researchers said.

There was a ``clinically significant adverse reaction'' between the ulcer drugs and Plavix, also known as clopidogrel, said Ronald Aubert, a researcher at Medco Health Solutions Inc., which funded the study. ``The proton pump inhibitor may inhibit the impact of clopidogrel, so it's like stopping therapy.''

Nexium was London-based AstraZeneca's top-selling product, generating revenue of $1.32 billion in the third quarter of this year. Plavix was Bristol-Myers's top-seller, with $1.44 billion.

AstraZeneca slipped 34 pence, or 1.2 percent, to 2,736 pence in London trading. Sanofi rose 31 cents, or 0.7 percent, in Paris trading to 7.70 euros. New York-based Bristol-Myers fell 34 cents, or 1.7 percent, to $20.04 at 4:15 p.m. in New York Stock Exchange composite trading.

Genetic Testing

U.S. regulators said in December they found no additional heart risks for patients taking Nexium and an older ulcer drug, Prilosec. The Food and Drug Administration said it saw no reason for doctors to change procedures after conducting a six-month review of 16 studies submitted by AstraZeneca.

The researchers at Medco, the largest U.S. drug benefits manager, recommended more studies to determine whether some patients may be genetically predisposed to complications.

Overall, proton pump inhibitors were associated with a 50 percent increase in the risk of heart attack, stroke, bypass surgery and cardiac-related death for Plavix users, the study found. People who took anti-clotting drugs alone had problems a fifth of the time.

The ulcer drugs also include Prilosec; Eisai Co.'s Aciphex; Wyeth's Protonix; and Prevacid, sold by Takeda Pharmaceutical Co. Complication rates were similar for each of the proton pump inhibitors, said the researchers, who didn't present numbers for the individual drugs.

Not Definitive?

The findings are ``by no means definitive,'' said Deepak Bhatt, chief of cardiology at the VA Boston Health Care System, who wasn't involved in the Medco study. The research was based on Medco's database of 19 million prescription users, and it won't change medical procedures unless the findings are duplicated in scientifically controlled studies pitting drug regimens against one another, he said in an interview.

``It's important not to sound the alarm prematurely,'' Bhatt said. ``I'm not changing therapy based on this but I am keeping my eyes open.''

The company's ongoing monitoring program and a review of past trials ``have not raised safety concerns'' about the Plavix- Nexium cocktail, Blair Hains, a company spokesman, said in an e- mailed comment today.

``Given the scientific limitations of retrospective database studies, AstraZeneca agrees that more research is needed before any conclusions can be drawn,'' he said.

Second Study

A second study released at the conference found patients on the ulcer drugs were more likely to die or have a heart attack or stroke regardless of whether took Plavix or a placebo.

Among patients getting both Plavix and a proton pump inhibitor, 13.2 percent had a cardiovascular complication, compared with 16.2 percent of those given the ulcer drug alone, researchers from the University of Kentucky in Lexington found.

The drug combination may not be the problem, Bhatt said. Instead, patients taking Nexium or its rivals may be older or have other conditions that raise their risks, he said.

To contact the reporter on this story: Alex Nussbaum in New York anussbaum1@bloomberg.net.

Last Updated: November 11, 2008 16:37 EST