In a finding sure to cause many cardiac patients some old-fashioned heartburn, researchers report that a commonly prescribed class of acid-blocking drugs interferes with an anticlotting medication routinely given to heart patients discharged from the hospital. The study, coupled with two earlier reports that have recently led to a stern warning from the U.S. Food and Drug Administration about mixing the drugs, might change doctors’ practices.
“A lot of us just prescribe things out of habit,” says study coauthor P. Michael Ho, a cardiologist at the Denver Veterans Affairs Medical Center. ”My hope is that this study makes physicians think twice.”
The new report, in the March 4 Journal of the American Medical Association, suggests that proton pump inhibitors (PPIs) neutralize more than stomach acid.
PPIs seem to inhibit the blood thinner clopidogrel, marketed as Plavix. Clopidogrel is a standard antiplatelet drug for people recently treated for heart problems. It doesn’t actually thin the blood, but it does discourage platelets from forming clots. That’s a boon for people with clogged coronary arteries that have been recently reopened.
Because clopidogrel can irritate the stomach in some patients, many doctors also prescribe a PPI such as Prilosec, Nexium, Aciphex, Prevacid and Protonix.
Ho and his colleagues reviewed the medical records of 8,205 people, nearly all men, who were prescribed clopidogrel upon discharge from Veterans Affairs hospitals between October 2003 and January 2006. These people had been treated for a heart attack or other serious heart problem, such as unstable angina, which causes chest tightness.
The records show that most were also prescribed a PPI upon discharge. After an average follow-up of 17 months, those getting both drugs were nearly twice as likely to be rehospitalized for a heart problem as those getting clopidogrel but not a PPI. Also, people getting both drugs were about 50 percent more likely to require a procedure to reopen a coronary artery. The scientists accounted for health differences between the groups including diabetes, lung disease, previous heart problems and dementia.
The researchers also ran a calculation after omitting anyone with previous stomach or intestinal bleeding. Even after eliminating this group, researchers found that people getting the combination of drugs were still about one-third more likely to experience a serious heart problem during the follow-up period than those getting clopidogrel without a PPI.
Clopidogrel must be activated by enzymes in the liver to work. But PPIs seem to shut off these enzymes and interfere with clopidogrel, says Robert S. Epstein, an epidemiologist and chief medical officer at Medco, a pharmacy benefits management company based in Franklin Lakes, N.J.
Non-PPI heartburn drugs that include Zantac, Pepcid, Axid and Tagamet didn’t have this effect in previous research and showed little correlation in this one.
“This is a very important paper,” Epstein says. “They did a very good job of weeding out — and adjusting for — differences between the groups.”
Epstein and his colleagues also recently found depleted clopidogrel action when it was coupled with a PPI, as did a Canadian team in a separate study. Based on those findings, the FDA issued a warning in January that doctors should continue to prescribe clopidogrel as an anticlotting measure but “should reevaluate the need for starting or continuing treatment with a PPI.” What’s more, the FDA said, “patients taking clopidogrel should consult with their health care provider if they are currently taking or considering taking a PPI,” including the over-the-counter Prilosec OTC.
Nearly 64 percent of patients in the new study were prescribed PPIs upon discharge. Epstein says his team found about a 40 percent rate. “People should really think twice about using these together,” he concludes.