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Mixing Plavix, Heartburn Drugs Seen as Risky

http://online.wsj.com/article/SB124165563240994165.html

By ALICIA MUNDY and JARED A. FAVOLE MAY 7, 2009

A cardiologists' group warned doctors to limit the use of popular heartburn pills in certain patients, citing a new study that says these pills raise the risk of heart attack by interfering with Plavix, an anticlotting medicine.

The warning affects a multibillion-dollar-a-year class of heartburn drugs known as proton-pump inhibitors, which include the widely advertised "purple pill," Nexium.

Doctors have expressed surprise at studies indicating some common heartburn drugs can interfere with Plavix, the world's most-widely used drug to prevent blood clots, WSJ's Alicia Mundy reports. The findings could affect millions of people taking Plavix and has drawn attention from the Food and Drug Administration.

The study by pharmacy-benefits company Medco Health Solutions Inc. and the Indiana University School of Medicine showed the four most commonly used proton-pump inhibitors boosted the risk of heart attack and stroke by 50% among cardiac patients taking Plavix. The other main proton-pump inhibitors are Takeda Pharmaeceutical Co.'s Prevacid, Wyeth's Protonix, and Prilosec OTC, an over-the-counter pill sold by Procter & Gamble. Plavix is co-marketed in the U.S. by Bristol-Myers Squibb Co. and Sanofi-Aventis SA.

The warning by the Society for Cardiovascular Angiography and Interventions in Washington targets only patients simultaneously taking one of the heartburn drugs and Plavix, not those taking a heartburn drug alone. Plavix is commonly prescribed for patients receiving a heart stent to prop open their arteries or those who have had a heart attack or stroke. Stomach bleeding and acid reflux are frequent side effects of Plavix. Doctors say about half the patients on Plavix take a proton-pump inhibitor to address those side effects.

The new study is the latest to raise concern among cardiologists and patients that the combination could be undermining Plavix's effectiveness. The evidence, coming a decade after Plavix first went on the market, is a reminder of how long it takes for doctors to learn about drug interactions that can hurt patients, even among widely taken drugs.

Lisa Barton, a part-time nurse in the Washington area, recently received a stent and went on Plavix. When she started suffering acid reflux, she asked her doctor about Nexium, which is often prescribed where she works. But her doctor, Ramin Oskoui, nixed Nexium and put her on a high dose of Zantac, a non-PPI heartburn pill that has been around 25 years.

"Dr. Oskoui told me that PPIs might interact with Plavix and cause my stent to clog," said Ms. Barton. Zantac, which is sold in generic form over the counter, is helping, she said.

AstraZeneca PLC, the maker of Nexium, said it is too soon to rule out use of Nexium in people taking Plavix. "There is a lot of conflicting data on this," said spokesman Blair Hains. He suggested people wait until the Food and Drug Administration issues more information. Mr. Hains said the Medco study, presented Wednesday at a meeting of the cardiovascular society, had limitations. The new study and earlier ones are retrospective, analyzing databases with patient information.

The makers of the other proton-pump-inhibitor drugs didn't immediately respond to requests for comment.

Paul Gurbel, a cardiologist at Sinai Hospital in Baltimore, said it may be the severe heartburn itself -- not the drugs taken to treat it -- that causes the additional risk. "Until we have a prospective study set up to answer this, we'll never have a definitive answer," said Dr. Gurbel.
[Heartburn Concerns]

Dr. Oskoui, vice chairman of internal medicine at Sibley Memorial Hospital in Washington, D.C., said he has "moved many patients to Zantac and Tagamet," another older, non-PPI drug. He said, "They are cheaper and avoid this concern. I haven't seen any cases of GI [gastrointestinal] bleeding in the patients I switched." He added, "In all candor, we probably were overprescribing PPIs with Plavix."

In a statement, the medical society said it "recommends the use of alternative medications for GI symptoms in patients with stents when appropriate." It said antacids as well as Zantac and Tagamet are effective heartburn treatments.

"This trend cannot be ignored," said the society's president, Steven Bailey. "We want doctors and patients to talk, but we think doctors must rethink this combination of drugs."

There are nearly one million heart-stent surgeries in the U.S. annually, according to the cardiovascular society. The FDA has been investigating whether Plavix's label needs to be updated to include data on possible interactions, and issued an alert to doctors in January. Plavix is the world's second-best-selling drug after Pfizer Inc.'s Lipitor cholesterol drug, with global sales of about $9 billion in 2008.

The Medco study could help a potential Plavix competitor called prasugrel, from Eli Lilly & Co. and Daiichi Sankyo Co. The efficacy of that drug, which is awaiting FDA approval, doesn't appear to be affected by proton-pump inhibitors.