Study: Drug Combo Raises Risks For Heart Patients

The anti-clotting drug Plavix is prescribed to just about everyone who's had a heart attack or received a stent. But now, researchers from the Denver VA Medical Center have identified a new and serious interaction between Plavix and anti-ulcer drugs called proton pump inhibitors, or PPIs.

The study looked at the records of more than 8,200 patients who had taken Plavix after a heart attack or heart procedure. About 60 percent had taken a proton pump inhibitor, usually Prilosec or Aciphex.

The anti-ulcer drugs are prescribed because Plavix can irritate the stomach.

But the combination may be risky. As the researchers report in the Journal of the American Medical Association, using Plavix plus one of the proton pump inhibitors raised the likelihood of returning to the hospital with more heart problems, or death from any cause, by about 25 percent.

The researchers, led by Dr. Michael Ho, say it appears that the anti-ulcer drugs interfere with the way Plavix reduces blood clotting, making it more likely that clots will form and heart problems will return.

Dr. Steven Nissen, chief of cardiovascular medicine at the Cleveland Clinic, says the risk is a concern. "When you have an interaction where one drug actually blocks the effectiveness of another drug that treats a serious disorder, you've got to take that seriously." He says hundreds of thousands, if not millions of people are on both drugs.

"Patients and physicians should reconsider why PPIs were prescribed in the first place," says Ho. "If the patients were having no stomach problems, they should use a different medicine, not a PPI."

Ho says his study highlights the importance of post-market surveillance — continuing to study a drug after it goes on the market. Often drugs are tested on relatively healthy people who aren't taking other, possibly interfering medications, and problems may only show up once the drug is being used by the general public.

Earlier this year, the Food and Drug Administration considered the possibility that PPIs might interfere with Plavix and recommended that health care providers think carefully before prescribing the two drugs together. The agency said health care providers should continue to prescribe Plavix because of its proven effectiveness in preventing blood clots that can lead to heart attacks and stroke.

Meanwhile, the FDA is considering whether to approve another drug, similar but not identical to Plavix, that prevents blood clotting. The decision could come within weeks or months. But it's not known whether PPIs interfere with that drug, too.

Transcript

MELISSA BLOCK, host:

From NPR News, this is ALL THINGS CONSIDERED. I'm Melissa Block.

ROBERT SIEGEL, host:

And I'm Robert Siegel. New research published today raises serious questions about the safety of two popular drugs. Both are used after heart attacks and heart procedures. As NPR's Joanne Silberner reports, the problems come when doctors use one of the drugs to prevent side effects caused by the other.

JOANNE SILBERNER: This is a story about an attempt to make things better that may have made things worst. It starts with the drug called Plavix. Plavix is one of the top selling drugs in America and it does great things, says Steven Nissen. He's head of cardiovascular medicine at the Cleveland Clinic.

Dr. STEVEN NISSEN (Head of Cardiovascular Medicine, Cleveland Clinic): We give Plavix for potentially life saving indications, to prevent clotting from occurring in a, say a stent, that has been put on the coronaries or after a heart attack to prevent the artery from getting a clot again.

SILBERNER: Both the American Heart Association and the American College of Cardiology recommend its use. But Plavix can irritate the stomach. So, here's the attempt to make things better. When doctors prescribe Plavix, they routinely prescribe something called an acid-blocker, like Prilosec or Aciphex. Scientists call these drugs proton pump inhibitors. They soothe the stomach by keeping acid down. That practice worried cardiologist Michael Ho. He'd seen a test tube study that showed the blood of people getting both Plavix and a proton pump inhibitor is more prone to clot.

So, Michael Ho and several colleagues of the VA Medical Centre in Denver studied records of more than 8,200 men treated at VA hospitals around the country with Plavix, also called clopidogrel.

Dr. MICHAEL HO (Cardiologist, VA Medical Centre): We found that patients who were on clopidogrel and proton pump inhibitors had an increased risk of another hospitalization for a heart attack or unstable coronary syndrome, compared to those who are just on clopidogrel alone.

SILBERNER: Plavix plus one of these acid blockers increase the risk of returning to the hospital or dying by 25 percent in the first year-and-a-half of taking the drugs. The researchers described the study in the current issue of the Journal of The American Medical Association. By medical standards, 25 percent is not a big increase until you consider that doctors prescribe Plavix to nearly every person who has had a heart attack or stent. And in the VA study, two thirds of men on Plavix land up on an acid blocker. Still, doctors should not stop prescribing Plavix, says Steven Nissen.

Dr. NISSEN: If you don't give Plavix to a patient with a stent in their coronaries, there is a high probability - much higher than we would accept -that they will get a clot in that stent, which will cause a heart attack or even death.

SILBERNER: And patients who've had heart attacks need that same anti-clotting benefit. Study author Michael Ho says the benefits of Plavix can still be had by limiting these particular acid blockers to a small group of patients with serious stomach problems.

Dr. HO: In other patients who don't have a clear indication, they may want to prescribe alternative stomach medication.

SILBERNER: Cardiologist Steven Nissen.

Dr. NISSEN: What this study does, is it puts us on notice. It says to the Cardiology community, there's a potentially serious problem here, it needs attention. You have to think about this now before you give these two drugs together.

SILBERNER: The Food and Drug Administration has been investigating the Plavix-acid blocker connection. Early this year, the agency recommended what doctors Ho and Nissen recommend: No automatic prescription of proton pump inhibitors like Prilosec when Plavix is prescribed.

Joanne Silberner, NPR News.