Aspirin vs. Plavix after upper GI bleeding

What a frustrating paper.

In last week’s NEJM is a study from the Prince of Wales Hospital in Hong Kong looking at clopidogrel versus aspirin and esomeprazole to prevent recurrent ulcer bleeding. More precisely, the authors studied patients who had been on 325 mg aspirin or less, who presented with upper GI bleeding and who were either H. Pylori negative or successfully treated. These patients were then randomized to either 80 mg of aspirin daily plus 20 mg of Nexium (esomeprazole) twice daily, or to 75 mg of Plavix alone. They were then followed for a year.

Recurrent upper-gastrointestinal bleeding occurred in 13 patients on Plavix and in only one patient on aspirin-Nexium. The authors’ last sentence: “Our observations do not support the current recommendation that clopidogrel be used for patients who have major gastrointestinal intolerance of aspirin”. The editorial in the same issue also discusses the question of what to do with patients who have had gastointestinal complications while taking aspirin, and says of the ACC/AHA recommendation to replace aspirin with clopidogrel: “The study by Chan et al. clearly indicates that this recommendation is harmful and that such patients should be given aspirin plus a proton-pump inhibitor.”

Not. At least, not exactly.

Patients who have just had a significant upper GI bleed while taking modest or low dose aspirin are clearly at a high risk for rebleeding, particularly if they are not on long-term acid suppression. So if you randomize these patients to either low-dose aspirin plus a PPI or to Plavix alone, it is not terribly surprising that the Plavix-only patients have a higher incidence of recurrent ulcer bleeding. This is a very unsatisfying comparison. On the one hand a drug, aspirin, that is clearly ulcerogenic and also promotes bleeding taken together with a drug that effectively prevents ulcers (omeprazole). On the other hand, a drug (Plavix) that may be less ulcerogenic but is even more likely to promote bleeding and given without any ulcer prevention. This comparison just muddies the waters. This study does not help distinguish the platelet-antagonizing effect of clopidogrel from any direct effect on the healing of ulcers.

Can anything be learned from this study? Mainly that, in patients with aspirin-induced upper GI bleeding who are H Pylori negative, Plavix should not be given alone as an alternative to aspirin plus a PPI.

It would seem that, in these patients, it is relatively safe to prescribe aspirin plus a PPI. Perhaps Plavix plus a PPI would be even safer, but this is pure speculation; this trial does nothing to address this issue one way or the other. What this means for patients who have gastro-intestinal intolerance of aspirin other than upper GI bleeding is unclear. Patients who have a good reason for being on clopidogrel (such as a recently implanted stent) should not be switched to aspirin plus a PPI alone if they have a GI bleed, at least not on the basis of this study.

Clopidogrel is a very popular and quite expensive drug, and I am annoyed by its overly aggressive promotion by drug reps, but this study doesn’t give me any ammunition in resisting its use.

4 thoughts on “Aspirin vs. Plavix after upper GI bleeding

  1. madhousemadman

    Well, I agree with you on the point concerning aspirin and PPI vs. clopidogrel alone and the fact that these comparisons are not fair. However, the current guidelines for patient who have bleeding complications with Aspirin calls for plavix ONLY therapy. So, did the study disprove that this is correct – I believe so.

    It is possible, nontheless, that plavix plus PPI is just as effective or maybe better than Aspirin plus PPI, but that remains to be seen. Unlike you, if I encounter another patient with UGI bleeding on ASA, my first intervention will no longer be switching to plavix. That is the point this article came to address.

  2. Pandrei

    I was similarly frustrated by this study. Another concern: How is the rate of lower GI bleeding the same in the two treatment arms? Aspirin has been shown to significantly increase the risk of lower GI bleeding, while clopidogrel (though with admittedly less extensive data) has not shown anywhere near the same degree of risk. My suspicion is that the study patients in both arms included a number of NSAID users–those in the esomeprazole arm would have been “protected” from upper but not lower GI bleeding.

  3. mjmd

    In response to the first comment: if I encounter a patient with upper GI bleeding on ASA, I would most likely switch to Plavix plus a PPI, not Plavix alone, although I admit there is no good data for this. I would just have a hard time continuing Aspirin with a history of recent UGI bleed, despite the results of this study. Of course everything depends on the specific clinical circumstances, as usual…

  4. TLC

    I am outraged at such ludicrous implications that plavix causes gi bleed.
    1. there was no arm where plavix was given with PPI
    2. this was a small study
    3. Plavix works on the adp receptor, ASA destroys the Prostaglandin protective layer of the stomach.
    3. I cant believe the NEJM published this study.

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