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UPDATE 1-Stent patients advised to switch heartburn drugs

Wed May 6, 2009 5:18pm EDT

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* Some reflux drugs reduce anti-clotting benefit of Plavix

* Increased risk of hospitalization seen in large study (Adds study details, doctor comments)

By Susan Kelly

CHICAGO, May 6 (Reuters) - A group representing cardiologists who perform stent procedures recommended that patients taking the blood thinner Plavix avoid certain acid reflux drugs after a study showed that combining the two raises the risk of heart attack or stroke.

Results of a large study presented on Wednesday at a meeting of the Society for Cardiac Angiography and Interventions (SCAI) in Las Vegas showed commonly used heartburn drugs called proton pump inhibitors (PPI) reduce the anti-clotting benefits of clopidogrel, the active ingredient in Plavix, when taken together.

In the study, patients taking Plavix, made by Bristol-Myers Squibb Co (BMY.N) and Sanofi-Aventis SA (SASY.PA), and a proton pump inhibitor experienced a 50 percent increase in the risk of hospitalization for heart attack, stroke, unstable angina or repeat stent procedure.

The study, conducted by pharmacy benefit manager Medco Health Solutions Inc (MHS.N), focused on four proton pump inhibitors: AstraZeneca's (AZN.L) Nexium and Prilosec, Takeda Pharmaceutical Co's (4502.T) Prevacid and Wyeth's WYE.N Protonix.

The researchers analyzed pharmacy and medical claims data from 16,690 patients taking clopidogrel for a year following stent implantation.

Clopidogrel, plus aspirin, is routinely prescribed to patients following the insertion of stents to prevent life-threatening blood clots. Heart organizations including SCAI recommend patients remain on the therapy for at least a year after receiving a stent, which is a tiny wire-mesh tube inserted into an artery that has been cleared of blockages.

Proton pump inhibitors, or PPIs, are frequently prescribed to patients after stent procedures to treat side effects of clopidogrel such as nausea. In some patients, the drugs may also be taken for gastrointestinal conditions such as peptic ulcer disease.

PPIs can interfere with enzymes in the liver that metabolize clopidogrel, reducing its anti-clotting effects, said Dr. Steven Bailey, SCAI's president-elect.

"We do know that PPI inhibitors do interfere with that liver enzyme process," Bailey said in an interview.

But he said more research is needed to determine which patients are likely to be most affected by the problem and whether newer proton pump inhibitors such as Aciphex and Kapidex react similarly.

The group recommended that stent patients use alternative medications for gastrointestinal symptoms when possible. Other treatments for heartburn and ulcers include histaminergic (H2) blockers such as Zantac and Tagamet or antacids.

AstraZeneca spokesman Blair Hains noted the U.S. Food and Drug Administration has asked the makers of clopidogrel for further information on the potential interaction of the two drugs. "There's lots of conflicting studies on evidence in this area," he said.

SCAI said two smaller, earlier studies came to opposite conclusions on the adverse effects of taking both medications. The first study, a database analysis, found an increase in cardiac events in patients taking clopidogrel and a PPI. A second study, called CREDO, found no adverse effects from the combination.

PPIs may still be warranted in patients who have stomach problems such as gastrointestinal bleeding and should be taken under the direction of a patient's doctors, SCAI advised. (Reporting by Susan Kelly; Editing by Tim Dobbyn)



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