Professional Soldiers ® - View Single Post - Plavix & PPI May Contribute to Heart Attack

shr7 · 03-09-2009, 16:42

Important to note that the study noted an increase by 25% of death or rehospitalization due to ACS in the Plavis plus PPI group as compared to the Plavix alone group. Just including a point of reference. You are still safer taking both medications than taking neither.

This particular possible interaction is of great interest to me as I spend about 50% of my day taking people off PPIs who do not need to be on them. (The other 50% is putting people on PPIs who do need to be on them.)

For a little background, Plavix (clopidogrel) is an anti-platelet medication that binds to the platelets in the bloodstream and prevents them from aggregating and forming clots. Aspirin is also an anti-platelet medication and is commonly used in combination with Plavix as they work in different ways. These medications are commonly used following hospitalization after acute coronary syndromes (ACS), where clots in the coronary arteries lead to less blood flow and less oxygen to the heart. Plavix usually being used for 1 year while the aspirin is continued indefinately.

PPIs (Prilosec, Prevacid, Aciphex, Protonix, Nexium), are usually started along with anti-platelet therapy to suppress acid production in the stomach in order to prevent ulcers and help promote coagulation in the stomach. Otherwise, with an acidic stomach and taking anti-platelet medication, if a GI bleed starts, it may never stop. The ACC/AHA recommendations in 2007 state that in patients with a history of GI bleed "when ASA (aspirin) and clopidogrel (Plavix) are administered alone or in combination, drugs to minimize the risk of recurrent gastrointestinal bleeding (e.g., proton-pump inhibitors) should be prescribed concomitantly."

In practice PPI use is very commonplace. Of the 5 listed above, Prevacid (8), Protonix (17), and Nexium (2) are all in the top 20 brand name medications by sales in 2007, while Aciphex, a relative newcomer is at #46. Omeprazole (Prilosec) is available as a generic and over the counter without a prescription.

Our understanding of this interaction is very limited at this time. Clopidogrel is inactive, it has to be activated by the liver in order to work and connect to the platelets. PPI's (some more than others) can inhibit some of the enzymes in the liver (CYP2C19). In addition, it is well recognized that patients in which this enzyme does not work as well do not respond as well to Plavix. The seemingly obvious conclusion is that the PPI's prevent this enzyme from activating Plavix and therefore it doesn't work as well.

Here is where it gets fuzzy. We don't know exactly what enzymes are responsible for activating Plavix. The prevailing theory is that it is an enzyme in the liver called CYP3A4. So why do patients with genetic abnormalities in the aforementioned CYP2C19 enzyme not respond well to Plavix. It is thought that this is due to the fact that patients with this genetic makeup also have abnormalities in their platelets that do not allow the Plavix to bind to them. So the question remains, then what is the mechanism of the interaction. And the answer is that we do not know. And we don't even know if there is an interaction at all.

This study published in JAMA was the first large study published on the topic. Yet it was still a retrospective epidemiological study. Patient baseline characteristics were not similar either. Patients in the group treated with both drugs had greater history of heart attack, heart failure, and lower incidence of surgical intervention, among many things. So this study, while very interesting, will probably not greatly change current prescribing practice to a great extent. Future studies may do that.

From the FDA back in January:
Until further information is available FDA recommends the following:

* Healthcare providers should continue to prescribe and patients should continue to take clopidogrel as directed, because clopidogrel has demonstrated benefits in preventing blood clots that could lead to a heart attack or stroke.
* Healthcare providers should re-evaluate the need for starting or continuing treatment with a PPI, including Prilosec OTC, in patients taking clopidogrel.
* Patients taking clopidogrel should consult with their healthcare provider if they are currently taking or considering taking a PPI, including Prilosec OTC.

Whether or not this study will change these recommendation I do not know. If it does, I expect a shift in these patient towards using Protonix for the PPI (which does not inhibit the enzyme CYP2C19 and has not been shown to interact with Plavix, or towards H2 blockers like Zantac or Pepcid.

One thing that I hope it does, however, is reinforce the notion that PPI's are not benign drugs. And I also hope that patients reading stories like this will look at their medication list and start to ask "do I need to be on these medications?" "Do any of these medications interact?" "Are there any side effects I need to be aware of?"

03-09-2009, 16:42	#3
shr7 Asset Join Date: Dec 2007 Location: Pittsburgh PA Posts: 50	Important to note that the study noted an increase by 25% of death or rehospitalization due to ACS in the Plavis plus PPI group as compared to the Plavix alone group. Just including a point of reference. You are still safer taking both medications than taking neither. This particular possible interaction is of great interest to me as I spend about 50% of my day taking people off PPIs who do not need to be on them. (The other 50% is putting people on PPIs who do need to be on them.) For a little background, Plavix (clopidogrel) is an anti-platelet medication that binds to the platelets in the bloodstream and prevents them from aggregating and forming clots. Aspirin is also an anti-platelet medication and is commonly used in combination with Plavix as they work in different ways. These medications are commonly used following hospitalization after acute coronary syndromes (ACS), where clots in the coronary arteries lead to less blood flow and less oxygen to the heart. Plavix usually being used for 1 year while the aspirin is continued indefinately. PPIs (Prilosec, Prevacid, Aciphex, Protonix, Nexium), are usually started along with anti-platelet therapy to suppress acid production in the stomach in order to prevent ulcers and help promote coagulation in the stomach. Otherwise, with an acidic stomach and taking anti-platelet medication, if a GI bleed starts, it may never stop. The ACC/AHA recommendations in 2007 state that in patients with a history of GI bleed "when ASA (aspirin) and clopidogrel (Plavix) are administered alone or in combination, drugs to minimize the risk of recurrent gastrointestinal bleeding (e.g., proton-pump inhibitors) should be prescribed concomitantly." In practice PPI use is very commonplace. Of the 5 listed above, Prevacid (8), Protonix (17), and Nexium (2) are all in the top 20 brand name medications by sales in 2007, while Aciphex, a relative newcomer is at #46. Omeprazole (Prilosec) is available as a generic and over the counter without a prescription. Our understanding of this interaction is very limited at this time. Clopidogrel is inactive, it has to be activated by the liver in order to work and connect to the platelets. PPI's (some more than others) can inhibit some of the enzymes in the liver (CYP2C19). In addition, it is well recognized that patients in which this enzyme does not work as well do not respond as well to Plavix. The seemingly obvious conclusion is that the PPI's prevent this enzyme from activating Plavix and therefore it doesn't work as well. Here is where it gets fuzzy. We don't know exactly what enzymes are responsible for activating Plavix. The prevailing theory is that it is an enzyme in the liver called CYP3A4. So why do patients with genetic abnormalities in the aforementioned CYP2C19 enzyme not respond well to Plavix. It is thought that this is due to the fact that patients with this genetic makeup also have abnormalities in their platelets that do not allow the Plavix to bind to them. So the question remains, then what is the mechanism of the interaction. And the answer is that we do not know. And we don't even know if there is an interaction at all. This study published in JAMA was the first large study published on the topic. Yet it was still a retrospective epidemiological study. Patient baseline characteristics were not similar either. Patients in the group treated with both drugs had greater history of heart attack, heart failure, and lower incidence of surgical intervention, among many things. So this study, while very interesting, will probably not greatly change current prescribing practice to a great extent. Future studies may do that. From the FDA back in January: Until further information is available FDA recommends the following: * Healthcare providers should continue to prescribe and patients should continue to take clopidogrel as directed, because clopidogrel has demonstrated benefits in preventing blood clots that could lead to a heart attack or stroke. * Healthcare providers should re-evaluate the need for starting or continuing treatment with a PPI, including Prilosec OTC, in patients taking clopidogrel. * Patients taking clopidogrel should consult with their healthcare provider if they are currently taking or considering taking a PPI, including Prilosec OTC. Whether or not this study will change these recommendation I do not know. If it does, I expect a shift in these patient towards using Protonix for the PPI (which does not inhibit the enzyme CYP2C19 and has not been shown to interact with Plavix, or towards H2 blockers like Zantac or Pepcid. One thing that I hope it does, however, is reinforce the notion that PPI's are not benign drugs. And I also hope that patients reading stories like this will look at their medication list and start to ask "do I need to be on these medications?" "Do any of these medications interact?" "Are there any side effects I need to be aware of?"
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