What is called drug-drug interaction can have a nasty outcome in this case - a study of 16,690 patients indicates that people who combine pills such as Nexium or Prilosec with the widely used Plavix blood thinner may have a 50 percent higher risk of a heart attack or other cardiac event than if only the blood thinner was taken.

The study, which was conducted by Medco Health, could have serious implications for millions of patients who take Plavix, given that many elderly combine who-knows-how-many pills every day. The irony is that a large number of patients on Plavix also take proton pump inhibitors, commonly called heartburn meds, to prevent stomach bleeding and ulcers, which are frequent side effects of Plavix.

One author of the study, Medco chief medical officer Bob Epstein, tells The Wall Street Journal this is an example of the “law of unintended consequences” that drugs intended to ease Plavix’s side effects also appear to blunt Plavix’s core purpose. The results are being presented this morning at the American Heart Association meeting and only an abstract is currently available. We are told that Medco will release more info shortly. UPDATE: Here is the Medco statement.

“This significant study presents a challenge for physicians,” AHA president Tim Gardner tells the paper. And Paul Gurbel, a cardiologist at Sinai Hospital in Baltimore, added: “It would be a real setback if it turned out that the main drug taken with Plavix is interfering with it.”

Last December, however, the FDA concluding Prilosec and Nexium don’t pose a risk of cardiovascular events after conducting a review of two long-term studies in patients with severe gastroesophagel reflux disease (GERD) who were being treated with either of the two proton-pump inhibitors (back story).

The new study, combined with two smaller studies published in the last year that had similar results, offers a theory to explain a mystery that has confounded doctors, the Journal writes. In 2003, Gurbel wrote in the journal Circulation that nearly 30 percent of Plavix patients don’t absorb the drug effectively. Since then, the FDA has been trying to understand the reason.

The mechanism remains unclear, but it appears heartburn meds may interfere with enzymes that help the body process Plavix, the paper writes. A spokesman for AstraZeneca, which makes Nexium, tells the paper that its monitoring program and a review of clinical-trial data “have not raised safety concerns to date” on use with Plavix.

Gurbel says if there is a choice between Plavix and a proton-pump inhibitor, docs should generally keep the patient on Plavix and drop the other drug because Plavix can prevent fatal heart attacks. “We rely on this drug to keep patients from having the most dreaded event,” he tells the paper. “Any potential interaction…is serious, and doctors need to look at whether they are directing patients to also take PPIs too much.”

The AstraZeneca spokesman declined to discuss the financial impact of the findings, writes the paper, which notes that Nexium was the fourth best-selling drug in the US last year with sales of $5.5 billion, according to IMS Health. It couldn’t be determined what percentage of Nexium users are also taking Plavix, but 25 million scrips were written for Plavix in 2007, and docs say as many as half of those on Plavix are taking a proton-pump inhibitor. Plavix sales were $4 billion last year.

The Medco study seems to undermine a report released last month by a task force for the AHA, the American College of Gastroenterology and the American College of Cardiology, which said proton-pump inhibitors “should be the mainstay of treatment and prevention of gastrointestinal ulcers and bleeding in patients on antiplatelet therapy.”

Medco’s Epstein hopes to meet with members of the task force “to them know what we found.” The pharmacy benefits manager began the study in January after its docs read one of the smaller studies, used its database of 19 million medical and drug claims, and worked with Indiana University researchers. The study is “very statistically significant for all major cardiac events,” he tells the paper.

Medco collected data on 16,690 patients over one year who needed a “cardiac intervention” such as a stent or a balloon and took Plavix, the Journal writes. Of those 6,828 also took a proton-pump inhibitor. The study found that about 18 percent in the Plavix-alone group had another cardiac event within a year of the original intervention, while nearly 25 percent of those taking both drugs had another cardiac event. Adjusted for risk factors of each group, the authors concluded that taking a proton-pump inhibitor raised risk of a cardiac event by 50 percent, according to the Journal.

According to Larry Lesko, director of the FDA’s clinical pharmacology division, the study shows why more research is needed into genetic and other factors that affect how patients respond to a drug. He said Asians, for example, don’t seem to respond well to Plavix. “This shows one-size-fits-all” isn’t the answer, though it is preferred by drug companies, he tells the paper, adding that the FDA is looking at Plavix and proton-pump inhibitors to determine “what can be done to best use both drugs safely if patients need them.”