Plavix, PPI Combo: Risky for Heart Patients?

Study Shows Risks of Combining Plavix and Proton Pump Inhibitors

By Salynn Boyles
WebMD Health News

Reviewed By Elizabeth Klodas, MD, FACC

March 3, 2009 -- Heart attack patients who take an acid-reducing proton pump inhibitor (PPI) drug like Prilosec or Nexium in combination with the antiplatelet drug Plavix are more likely to have a second heart attack than patients who don't take PPIs, according to new research.

The findings confirm several smaller trials and one larger one, reported just weeks ago, suggesting that PPIs can inhibit the blood clot-inhibiting activity of Plavix, also known as clopidogrel.

Heart patients in the study who took Plavix with a PPI had a 25% increased risk of dying or of requiring hospitalization for heart-related issues, compared to patients who took Plavix alone, says study researcher P. Michael Ho, MD, PhD of the Denver VA Medical Center. Even after adjusting for factors such as patient age and other health factors, the concomitant use of Plavix and a PPI was still associated with a substantially higher risk of subsequent heart attacks or need for revascularization procedures.

The study appears in the March 4 issue of The Journal of the American Medical Association.

"It is increasingly clear that PPIs should not be prescribed to patients taking clopidogrel unless there is a good indication for doing so," Ho tells WebMD.

PPIs Routinely Given With Plavix

Along with aspirin, Plavix is routinely prescribed after a heart attack or as part of treatment for heart conditions like unstable angina to prevent potentially life-threatening blood clots from forming.

PPIs, such as Prilosec, Nexium, Prevacid, Aciphex, and Protonix, are often prescribed as well to reduce the risk of gastric bleeding from the blood-thinning combination treatment.

But several recent studies suggest that patients who take Plavix and PPIs together have an increased risk for recurrent heart attacks and death from other heart-related causes.

In an effort to shed light on the issue, Ho and colleagues followed more than 8,000 patients treated for heart attacks or unstable angina at 127 Veterans Administration hospitals across the country.

Plavix was prescribed to all the patients, and 64% were prescribed a PPI.

Over three years of follow-up, about 30% of the patients who took Plavix plus a PPI either died or were hospitalized for heart-related causes, compared to 21% of the patients who took the antiplatelet drug without a PPI.

Taking Plavix with a PPI at any time during the follow-up was associated with a 25% increase in risk for death or hospitalization.

American Heart Association president Timothy Gardner, MD, tells WebMD that it is now clear that PPIs should be prescribed cautiously to heart patients taking Plavix.

"If a patient has a history of GI bleeding, we know that [Plavix] can increase the risk of recurrence," he says. "It may be that we need to limit the use of PPIs to these patients and other patients who have a clear need for protection."

Are All PPIs Equal?

Findings from a large Canadian trial, reported in late January, suggest that all PPIs are not equal when it comes to inhibiting the antiplatelet activity of Plavix.

The study included more than 13,000 heart attack patients treated with Plavix with or without a PPI.

Study researcher David N. Juurlink, MD, PhD, tells WebMD that although most PPIs did appear to interact with Plavix, one -- Protonix (pantoprazole, Wyeth Pharmaceuticals) -- showed no evidence of reducing the effectiveness of the antiplatelet drug.

Juurlink says he received no funding from Wyeth or any other drug company to conduct his research.

"Literally millions of people who are taking Plavix and aspirin are also taking a PPI," he says. "If a patient on Plavix requires a PPI, it would seem to make sense to preferentially give them pantoprazole."

In late January, the FDA announced that Plavix manufacturers Bristol-Myers Squibb and Sanofi-Aventis had agreed to conduct studies to clarify the impact of PPIs and other drugs on the effectiveness of Plavix in heart patients.

"Patients taking clopidogrel should consult with their healthcare provider if they are currently taking or considering taking a PPI, including Prilosec OTC," the statement noted.

Wyeth Pharmaceutical spokeswoman Gwen Fisher tells WebMD that the company is awaiting the results from these trials.

A spokesman for AstraZeneca, which makes Prilosec and Nexium, tells WebMD that rigorously designed, prospective studies are needed to determine if PPIs interact with Plavix.

"To date, there have been contradictory conclusions and scientific limitations in studies about the potential interaction between clopidogrel and PPIs," AstraZeneca spokesman Blair Hains says. "AstraZeneca believes that before definitive conclusions are drawn, more evidence involving thorough, well-designed, prospective clinical trials is needed."

Calls to Plavix manufacturer Bristol Myers Squibb were not returned by publishing time.

SOURCES: Ho, M.P. The Journal of the American Medical Association, March 4, 2009; vol 301: pp 937-944. P. Michael Ho., MD, PhD, assistant professor, University of Colorado at Denver. David Juurlink, BPhm, MD, PhD, head, division of clinical pharmacology and toxicology, Sunnybrook Health Sciences Center, Toronto. Timothy J. Gardner, MD, president, American Heart Association. FDA statement on safety review of Plavix, Jan. 26, 2009. Gwen Fisher, public relations, Wyeth Pharmaceuticals. Juurlink, D.N. CMAJ Online, Jan. 28, 2009.

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