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Richard N. Fogoros, M.D.

More Evidence of Problems With PPIs and Plavix

By May 11, 2009

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A new study has added to the concern that commonly used proton-pump inhibitors (PPIs) may interfere with Plavix in people who have coronary artery disease.

Plavix (clopidogrel) is an important anti-platelet drug that is used extensively to help prevent blood clotting (thrombosis) in patients with coronary artery disease. Plavix is most often used in treating acute coronary syndrome (ACS), which encompasses conditions like acute heart attack and unstable angina, and after the placement of stents in order to prevent stent thrombosis. Plavix is the second most-prescribed drug in the United States.

Plavix often causes heartburn symptoms, so PPIs have been prescribed commonly in people taking this drug. In fact, guidelines published by several professional societies actually recommend PPIs in patients taking Plavix, in order to prevent gastrointestinal ulcers that may be particularly prone to bleeding in people on anti-platelet drugs. PPIs available by prescription include Prilosec and Zegerid (omepromazole), Prevacid (lansoprazole), Protonix (pantoprazole), Aciphex (rabeprazole), and Nexium (esomeprazole). Prilosec is also sold over-the-counter for heartburn.

A little more than a year ago, evidence emerged that commonly-used proton-pump inhibitors might significantly reduce the effectiveness of Plavix in patients with coronary arteyr disease. At that time, in a retrospective study of 8205 patients with ACS, those who were discharged on both Plavix and a PPI had a 25% increased risk of death or rehospitalization for recurrent ACS than patients treated with Plavix alone.

And last week, at the Scientific Sessions of the Society for Cardiovascular Angiography and Interventions (SCAI), the largest study yet (over 16,000 patients) again suggested that using PPIs may pose a problem for patients with coronary artery disease who are taking Plavix. In this study, the risk of developing major cardiovascular events (such as heart attacks) was significantly higher for those also taking Prilosec, Zegerid, Nexium, Protonix, or Prevacid. (Too few patients were taking Aciphex in this study to reach any conclusions about that particular PPI.)

So far, all the studies correlating the use of PPIs with a reduced effectiveness of Plavix are retrospective and observational, and so cannot prove a cause-and-effect relationship. However, the evidence is now strong enough that the SCAI has just revised its recommendations. This organization now recommends that physicians avoid prescribing PPIs in patinets taking Plavix unless it is considered very necessary, and instead, whenever possible, use alternative medications for treating gastrointestinal symptoms, such as histaminergic (H2) blockers like Zantac or Tagamet, or antacids.

If you are taking Plavix for any reason, you should discuss this issue with your doctor before agreeing to take any of the PPIs by prescription, or over-the-counter.

May 18, 2009 at 11:20 am
(1) Vernon says:

I didn’t read the article, I thought it was done by an MD since they have this same attitude when you take Vitamins which they call ‘Supplements’ and then if there are any problems, they normally blame the non drugs and they think the drugs are awesome and although I take some drugs which are very helpful, I am tired of my doctor asking or requesting me to take this or that and I can’t trust my doctor to tell him I take Vitamins although my blood pressure is much better with one less drug and 2 Vitamins compared to taking 7 drugs in the morning and I took off one of the drugs in the afternoon and my foot doctor, I said to her about the cream on my foot after putting some soap which another friend of mine whose diabetic and had an injury and it has been very helpful and has worked with the cream although the antibiotic made what I was doing work even faster, but she said this cream was a waste of money, but I know better since I have seen the foot healer better. I hope your not offended since I am glad for the many times my doctor has helped and yet I have found my blood work tests and worked on them and improved most of them without his help, but I am NOT a doctor and so I know there are times I will need help with drugs. I am glad you had an example which was not biased against non drugs, and this was just two drugs and how they don’t work together. I am going to try to read another message from you and try to be open minded about all of this. I read some of the article and I had a blood clot myself and they have all kinds of fancy names for them, and I took a generic pill for it and I have read since that time that many of these pills can be very dangerous, this was one time I was confident this was safe, but although the news is always changing, I would concede this is a good reason I am not a MD since whats good today might be unsafe for the next day.

May 19, 2009 at 12:28 am
(2) Dr.K.Ramadas says:

I am a scientist involved in medicinal chemistry and in drug-drug interactions with structural implications.
The thienopyridine derivative, prodrug plavix is prevented in its conversion to the actual drug through ring-opening and subsequent interactions due to the presence of the benzimidazole based PPIs; however, being a patient myself with GI problems space the intake of plavix and the azole; I also noted by experience that esomeprazole does not interfere as much as other PPIs do.; besides,the suggestion to resort to other drugs such as zantac and antacids holds no value in cases where the GI problems are not set at rest by these.
Dr K. Ramadas

May 25, 2009 at 10:23 am
(3) LisaCaroline says:

Bieng a PPI and Plavix patient naturally I was disturbed in this finding. I did have an ACS event 9 months from the stenting and the start of Plavix. Heartburn became almost daily so Nexium was added 6 months post stenting. I do not know if the ACS was due to the combo but I am not taking any chances. My doctor said to substitute Nexium with Maalox and Zantac/Pepcid. This combo is not Nexium. What I am doing now is Plavix every other day since it remains in the body for about 4 days and Nexium on the days I do not take the Plavix. Right or wrong, I have to do what my body feels is best for “me”. This is not carved in stone.

June 22, 2011 at 10:38 pm
(4) joe egbert says:

I agree with you Dr. Ramadas along with Lisa Caroline , it seems Bristol Myers is doing well enough $$$$$$$$$$$$$$ with this one , patent extensions etc. etc. , who’s pocket are they going to grease next ? it seems they’ve greased the FDA already besides PICKING ours at $200 a month . What a world we live in .

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