Problems with Plavix

Drugs have side effects. This is not a news bulletin.

Prior to releasing a drug, companies do studies and report side effect profiles. Post marketing surveillance often uncovers additional problems.

Study Raises Questions on Plavix Safety

Patients taking Plavix, a popular and expensive antistroke drug, experience more than 12 times as many ulcers as patients who take aspirin plus a heartburn pill, a study to be published today in The New England Journal of Medicine found.

Up to half of those now taking Plavix do so because their doctors assume that Plavix is safer on the stomach than aspirin, said Dr. Francis K. L. Chan, the study’s lead author. Both the American College of Cardiology and the American Heart Association recommend that heart and stroke patients at risk of developing ulcers be given Plavix instead of aspirin.

The new study suggests that the guidelines should be changed, and that many of those who are taking Plavix should consider switching to aspirin plus a heartburn pill because it is not only safer but cheaper, Dr. Chan said.

“Plavix might really damage the stomach,” Dr. Chan said.

Reports like this make the news, especially the financial news.

The challenge that clinicians and clinician scientists must understand involves putting each new data piece into perspective. Several questions come to mind immediately, prior to reading the remainder of the article:

• Would PPIs (proton pump inhibitors) also decrease ulcer rates in Plavix treated patients?
• Which patients really benefit from Plavix? What duration of therapy should we use?
• How important were the ulcers (did they bleed, cause pain, or were they “incidental” findings)?

Readers will probably have other good questions.

So here is the rest of the story:

Aspirin sells for less than 10 cents a pill. Plavix sells for between $3 and $4 a pill. Tests underwritten by Sanofi-Aventis suggest that Plavix may be slightly better than aspirin at preventing strokes. But the huge popularity of Plavix has also resulted, in part, because it has long been considered safer on the stomach than aspirin.

Dr. Chan said he was surprised to find that almost no studies had been done to confirm whether this assumption was true. He found 320 patients whose ulcers had healed and gave half of them Plavix and half of them aspirin plus Nexium, a heartburn pill. He followed them for a year.

Thirteen of the patients taking Plavix, or 8.6 percent, experienced renewed ulcer bleeding during the year while just one, or 0.7 percent, of those taking aspirin and Nexium had an ulcer bleed.

“That’s an astonishingly high rate of bleeding ulcers” in the Plavix group, said Dr. Bryon Cryer, associate professor of medicine at the University of Texas Southwestern Medical School and author of an editorial on the Chan study in tomorrow’s Journal.

“This observation is astonishing enough to lead physicians to rethink their preferred treatment strategies to prevent cardiovascular disease in patients with histories of previous ulcers,” Dr. Cryer said.

Reading the rest of the story makes us a bit more skeptical of the importance of this study. We know that ulcer patients have recurrences. We know that PPIs can prevent ulcer recurrence. We know that ulcers bleed, and that Plavix treated patients are more likely to bleed (it causes platelet dysfunction).

So I give this study a big – DUH!

This is the wrong study. The results make Plavix look bad, but it does not answer the key questions:

• Given a patient with NO ulcer history – does Plavix induce ulcers?
• How would a combination of Plavix + a PPI compare with ASA + a PPI in patients with previous ulcer?

We clearly should understand the risks of Plavix, but this article does not really help. Most patients who receive Plavix, do so for clear indications. We need to understand side effects in patients who resemble our patient populations.