A study suggests that some heartburn drugs may reduce the effectiveness of a popular medication used to prevent blood clots in people at risk for heart attacks and strokes.

Researchers focused on the effects of heartburn drugs known as proton pump inhibitors (PPIs), specifically looking at four that accounted for about 96 percent of PPI use in the study: omeprazole (Prilosec), esomeprazole (Nexium), pantoprazole (Protonix), and lansoprazole (Prevacid).

The results showed the benefits of the anti-clotting medication clopidogrel (Plavix) were reduced by these common heartburn drugs, resulting in a roughly 50 percent increase in the combined risk of hospitalization for heart attack, stroke and other serious cardiovascular illnesses.

The investigators say that proton pump inhibitors appear to block certain liver enzymes that covert clopidogrel into its active form in the body, reducing its effectiveness.

The study, conducted by Medco Health Solutions Inc, a pharmacy benefits management company based in New Jersey, and the Indiana University School of Medicine in Indianapolis, was presented in May at the annual meeting of the Society for Cardiovascular Angiography and Interventions in Las Vegas, Nev.

“The PPIs, analyzed together, do seem to be associated with a higher rate of cardiovascular impacts for those patients who are on Plavix, compared to those who are on Plavix alone,” says Eric Stanek, PharmD, the study’s principal investigator and senior director of personalized medicine research at Medco Health Solutions.

Researchers analyzed data on pharmacy and medical claims from more than 10 million patients, including 16,690 patients taking clopidogrel for a full year following coronary stenting. Of these, 41 percent also took a PPI, on average, for more than nine months of the year. Over that 12-month period when patients took clopidogrel, investigators evaluated the risk of hospitalization for major adverse cardiovascular events, which they defined as a combination of heart attack, unstable angina, stroke or temporary stroke-like symptoms, repeat coronary procedures or cardiovascular death.

The overall risk was 51 percent higher among patients taking any PPI. When individual PPIs were considered, omeprazole (Prilosec) was associated with a 39 percent increased risk; esomeprazole (Nexium) was tied to a to a 57 percent increased risk; and pantoprazole (Protonix) was linked to a 61 percent increased risk; and lansoprazole (Prevacid) was associated to a 39 percent increased risk.

“Though they may differ numerically, in truth, statistically they are all very similar,” Stanek says. “All of them seem to behave similarly in terms of association with higher risk of cardiovascular events in patients on Plavix.”

This study looked at patients prescribed clopidogrel after surgery to insert a heart stent to keep their arteries open. But researchers say they know many rheumatoid arthritis patients also take this drug combination.

So what should patients do? Stanek says they should meet with their doctors to discuss the balance of risk and benefit between the drug combination. “If you are on Plavix, stay on Plavix as prescribed,” he says. “It’s not an emergency. But I would definitely confer with my prescriber.”  

Drug makers have suggested that people wait until the Food and Drug Administration issues more information. But the Society for Cardiovascular Angiography and Interventions, in Washington D.C., issued a warning for patients taking heartburn drugs with clopidogrel.  They say doctors, when possible, should switch patients on clopidogrel to other effective, non-PPI drugs for heartburn and ulcer treatment like ranitidine (Zantac) and cimetidine (Tagamet).

Donald R. Miller, PharmD, is a professor and chair of the Pharmacy Practice Department at the College of Pharmacy at North Dakota State University in Fargo. He says some people might want to switch to aspirin instead of clopidogrel. He agrees that patients on these medications should discuss the topic with their doctor or pharmacist. “There is more and more accumulating data that suggest that PPIs lower the effect of Plavix. So if you aren’t getting the full effect, then you would be at a higher risk of heart attack,” Miller explains.

He also says that even though the study did not study rheumatoid arthritis patients, the drug combination lowers the active amount of Plavix in the blood.” No matter what you are taking it for, it would be an issue for everybody,” he said.

Stanek says that going forward, more research is needed to see if newer, less widely used PPIs like rabeprazole sodium (Aciphex) and dexlansoprasole (Kapidex) have the same increased cardiovascular risk. He also wants to see if there’s a genetic component that could affect the medicine combination.