Anticoagulants and PPIs

[DianaCox]

I have seen in several places, possible from the same source, that PPIs can be used with anticoagulants. @west4thavenue Ave - you posted on PB:

My surgeon wants his patients on a PPI for six months following surgery. Unfortunately, I cannot take them because they are contraindicated when taking blood thinners. He says it is to protect the stomach while it is healing. Sounds like a good precautionary measure to me.

But I think that is exactly the OPPOSITE of good advice!!

When you are on anticoags, you are more likely to bleed. When your stomach is newly operated on, and raw, and acid is irritating it, you are more likely to get a GI bleed! PPIs reduce the risk of getting a GI bleed!

http://www.ncbi.nlm.nih.gov/pubmed/18607297

J Clin Gastroenterol. 2009 Jan;43(1):5-12. doi: 10.1097/MCG.0b013e31811edd13.
Gastrointestinal bleeding in the setting of anticoagulation and antiplatelet therapy.
Barada K1, Abdul-Baki H, El Hajj II, Hashash JG, Green PH.
CONCLUSIONS:
Predictors of bleeding on antiplatelets and/or antithrombotics therapy have been identified, but formulation and validation of a GI bleeding index for stratification of risk in individual patients is suggested. Reversal of anticoagulation in bleeding patients is associated with a low risk of thromboembolic events and permits the performance of diagnostic and therapeutic endoscopy. Proton-pump inhibitors and H. pylori eradication reduce the risk of rebleeding in those with acid-related disease.

http://www.medscape.com/viewarticle/820935
Do Patients on Anticoagulants Also Need Acid Suppressants?
Devada Singh-Franco, PharmD
February 27, 2014
Question
Which patients are appropriate candidates for gastroprotection with acid-suppressive therapies?
Anticoagulants
Previous gastrointestinal bleeding, presence of H pylori infection, and concomitant medications associated with UGI (eg, NSAIDs, corticosteroids) should also be considered. Strategies to reduce bleeding include correcting modifiable characteristics (eg, labile INRs, alcohol use, and hypertension) and adding a PPI for gastroprotection.[7,9,11]

The only exception that I saw was this:
http://www.medindia.net/news/Big-No...flux-Tablets-After-a-Heart-Attack-85911-1.htm
Heart attack patients who are given a blood thinner (aspirin) and a proton pump inhibitor (PPI) like omeprazole or pantoprazole maybe at increased risk of getting another cardiovascular event, as per a new study.

Read more: Big No to Combining Blood Thinners With Acid Reflux Tablets After a Heart Attack | Medindia http://www.medindia.net/news/Big-No...fter-a-Heart-Attack-85911-1.htm#ixzz30t39G3iq
"Usually, as a course of treatment, patients are given aspirin to inhibit platelet aggregation after a first heart attack as a blood thinning agent to help reduce the risk of another heart attack. Along with, several doctors prescribe PPIs (proton pump inhibitors, drugs used to help prevent gastric acid reflux) as well for the prevention of peptic ulcers in patients treated with aspirin.

The study team, led by Dr. Mette Charlot of Copenhagen University Hospital, Denmark studied a large number of patients admitted to the hospital with their first episode of myocardial infarction. A total 19,925 patients were prescribed aspirin within 30 days of discharge and excluded the ones who took clopidogrel (an antiplatelet/clotting agent). Of these, 4306 were prescribed for pump inhibitor (PPI) within one year.

During the follow-up, 3366 out of the 19,925 patients experienced recurrent MI, stroke, or even death following a cardiovascular event.

Study reports indicated that the overall rate of adverse Cardiovascular Events (CV) was significantly much higher among patients who were taking aspirin and a PPI, than in those who took aspirin alone. This also holds true for each of the three adverse events analyzed separately."

But it is not the combination that is inherently dangerous - it is only after heart attack.

 

[Larra]

To west4thavenue - almost everyone needs PPI's or some other med for at least awhile after their surgery. In addition to the excellent advice Diana has given you here, why not check with your pcp or cardiologist or whoever prescribes the anticoagulants for you to make sure you can take a PPI? Do it now, while you're still pre-op, so that when you need them there will be no delay.
And if you really can't take them, ask about Tagamet or zantac. These are somewhat older but still very effective drugs for acid that are not PPIs - different class altogether, and hopefully something you can use.

 

[Munchkin]

Glad I have never take any of these!

 

[Spiky Bugger]

And...the GI docs are bickering among themselves (you can read it at pub med) over whether PPIs are a contributing factor to C Diff. Jury seems to still be out.

 

[kirmy]

PPI's are going to be found out one day as having such far reaching effects...mark my words! It is wondrous how they work and without them post surgery I'd be utterly lost but as soon as my acid was under control I binned them. I'm not personally for these long term. That's just my gut instinct.

 

[west4thavenue]

Thank you for looking into this. It makes me feel good that someone cares.

I started taking Zantac again. Aspirin is part of my regimen. More importantly, I am taking Clopidogrel, and will have to take this for the remainder of my life. My cardiologist has said no PPIs. I found this explanation why on Medscape.com:

"PPIs decrease effects of clopidogrel by affecting hepatic enzyme CYP2C19 metabolism. High likelihood serious or life-threatening interaction. Contraindicated unless benefits outweigh risks and no alternatives available. Clopidogrel efficacy may be reduced by drugs that inhibit CYP2C19. Inhibition of platelet aggregation by clopidogrel is entirely due to an active metabolite. Clopidogrel is metabolized to this active metabolite in part by CYP2C19."

Given the choice between the benefits of antiplatelets and PPIs, I am choosing to live with an irritated stomach that is slower to heal. A blockage to the blood supply to my left optic nerve has been detected, which means I am currently at risk for stroke or eye stroke. I go in for testing next week to see if there is anything that can be done about that beyond the meds I am now taking. I am having a rough ride right now, I won't lie. However, I am alive and fighting to stay that way.

I am feeling better! Progress is slow, but it is still progress. Thank you so much for your concern.

 

[Kate]

@west4thavenue I am glad you are feeling better and I hope that things improve even more for you soon! Keep us posted on the results of your testing next week. (((HUGS)))

 

[Larra]

West4thavenue, I'm glad you're doing better, albeit slowly, and glad you have started a good alternative to taking a PPI. There is nothing wrong with Zantac. Before PPI's came along, zantac and Tagamet were among the most commonly prescribed drugs in the USA.

We tend to recommend PPI's very freely because they are generally safe and they help so many of us, esp as early post-ops. But clearly they are not a good choice for everyone. It's a good reminder to us that medical care needs to be individualized.

 

[Spiky Bugger]

PPI's are going to be found out one day as having such far reaching effects...mark my words! It is wondrous how they work and without them post surgery I'd be utterly lost but as soon as my acid was under control I binned them. I'm not personally for these long term. That's just my gut instinct.

Too cute.

 

[JackieOnLine]

yes, that's good.

I'm afraid you are right - afraid being the word since I can't get off them. I might could cut them in half if I could cut back on coffee....but that isn't going to happen.

 

[Terri]

Thank you for looking into this. It makes me feel good that someone cares.

I started taking Zantac again. Aspirin is part of my regimen. More importantly, I am taking Clopidogrel, and will have to take this for the remainder of my life. My cardiologist has said no PPIs. I found this explanation why on Medscape.com:

"PPIs decrease effects of clopidogrel by affecting hepatic enzyme CYP2C19 metabolism. High likelihood serious or life-threatening interaction. Contraindicated unless benefits outweigh risks and no alternatives available. Clopidogrel efficacy may be reduced by drugs that inhibit CYP2C19. Inhibition of platelet aggregation by clopidogrel is entirely due to an active metabolite. Clopidogrel is metabolized to this active metabolite in part by CYP2C19."

Given the choice between the benefits of antiplatelets and PPIs, I am choosing to live with an irritated stomach that is slower to heal. A blockage to the blood supply to my left optic nerve has been detected, which means I am currently at risk for stroke or eye stroke. I go in for testing next week to see if there is anything that can be done about that beyond the meds I am now taking. I am having a rough ride right now, I won't lie. However, I am alive and fighting to stay that way.

I am feeling better! Progress is slow, but it is still progress. Thank you so much for your concern.

Even though it is a little slow you are moving forward, so that is good. Sending positive thoughts for your tests next week and please keep us updated.

 

[DianaCox]

Thank you for that explanation. It seems it is not a problem with anticoagulants generally, but clopidogrel specifically.

Here is a very recent update: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3975086/

The Cytochrome P450 Enzyme System
Discussion of interactions with intestinal and liver CYPs was extensive in the 2006 review [10] and is not reiterated here, except to remind readers that PPIs are predominantly metabolised in the liver by CYP2C19 and CYP3A4 [27].

Of significance since the previous review, there have been extensive discussions in recent reviews and meta-analyses on the drug interactions between certain PPIs and clopidogrel [28–34]. These interactions appear to be mediated by CYP2C19 and are of utmost clinical relevance. Although recent retrospective studies have suggested an attenuation of the beneficial effects of clopidogrel when administered concomitantly with PPIs in general, stratification of the analysis has indicated that such effects are not present in patients receiving pantoprazole-Na compared with those receiving omeprazole [35, 36]. Several studies demonstrated that being in steady state for omeprazole significantly increased total exposure to clopidogrel and decreased exposure to the active metabolite [37]. These effects continued to persist even after separating administrations of the drugs by 12 hours, or after administration of doubled doses of clopidogrel. However, differences became clearly smaller after substitution of omeprazole by pantoprazole-Na [37].

This is consistent with the finding that clopidogrel must be activated by CYP2C19, an enzyme inhibited by omeprazole but not pantoprazole-Na [38]. It is further confirmed by data showing that exposure to the active metabolite after administration of clopidogrel was significantly decreased, and inhibition of platelet function diminished, under coadministration of omeprazole or esomeprazole [39]. The relevance of CYP2C19 is further stressed by a study showing that only a small effect was observed from coadministration of lansoprazole with prasugrel, the latter being activated more dominantly by CYP isoenzymes other than CYP2C19 [40].

The situation for lansoprazole seems more complex; however, unlike for rabeprazole, at least some information, including pharmacokinetic data, is available. Coadministration of lansoprazole with clopidogrel had no effect on the formation of clopidogrel’s inactive carboxylic acid metabolite. Nonetheless, the pharmacodynamic effect was significantly lowered in good responders to clopidogrel, probably as a result of inhibition of clopidogrel activation via CYP2C19, which is without relevance for the formation of the carboxylic acid derivative via esterases [40]. However, evaluation of the total population in this study did not show more than a trend to a lowered efficacy of clopidogrel. This is consistent with findings reported from another study which found lansoprazole or dexlansoprazole exhibited no significant effect on the exposure to clopidogrel’s active metabolite or its pharmacodynamics [39].

In summary an interaction between clopidogrel and PPIs seems to exist for omeprazole and esomeprazole, whereas there are only limited data for rabeprazole. Dexlansoprazole, lansoprazole and pantoprazole-Na had less effect on the antiplatelet activity of clopidogrel than did omeprazole or esomeprazole, which is supported by the Plavix label [41].

 

[hilary1617]

As head's up, my oncologist/endocrinologists office published a study demonstrating that chronic PPI use is associated with significantly elevated gastrin and chromogranin A (CGA) levels. This can complicate use of blood tests to diagnose certain conditions like gastrinoma.

 

[JackieOnLine]

folks, I need this info summarized in a less complicated way
*cough*dumbed-down*cough*

Diana, so I should look for another PPI rather than omeprazole? why should I care about antiplatlet activity?

chronic PPI use is associated with significantly elevated gastrin and chromogranin A (CGA) levels

should this matter to me if I don't have a need for blood tests that might be affected?

 

[DianaCox]

folks, I need this info summarized in a less complicated way
*cough*dumbed-down*cough*

Diana, so I should look for another PPI rather than omeprazole? why should I care about antiplatlet activity?

should this matter to me if I don't have a need for blood tests that might be affected?

I don't think it matters unless you are using clopidogrel. And I don't think you need to care for THIS reason at all, unless you are on some sort of blood thinner meds.

As for the OTHER reasons - I simply don't know, and I take twice the usual dose of Protonix per day. I guess I should start paying attention and doing some research.