Compromising Combinations

As disturbing as it might be to me, it appears that the FDA does not read my blog. I have written several times about the controversy concerning the combination of the drugs Plavix and the proton pump inhibitors. I and many other more prominent and learned cardiologists than I thought the controversy was resolved by the publication of the articles mentioned in my last blog on the subject.On November 17 during the American Heart Association meeting in Orlando, the FDA issued a public health warning on the “possible interaction” between Plavix and one proton pump inhibitor Prilosec.

Apparently the FDA was not swayed by the data from COGENT which I have reviewed in previous blogs. Maybe they know something that we have not been told. They have required the manufacturers to update the label of Plavix. The “label” is that piece of folded up tissue paper that you sometimes get with new drug prescriptions that is written in micro type and reads like Greek.

It should be noted that although no other members of the proton pump inhibitor class were mentioned, the drugs that the FDA recommended to use with Plavix are the H2 antagonists such as Pepcid or Zantac. Tagamet cannot be used as it is metabolized the same pathway that Plavix is and will have the same consequences that the use of Prilosec will.

If you are taking Plavix and need help with the risk of GI bleeding your doctor will be the person to ask what you should do. The “safest” decision may be to take the H2 blockers mentioned and forget about it. If doctors other than your primary doctor or cardiologist try to put you on other medication, it is your responsibility to help us and tell us all the medications you are on. It is always a wise idea to check with your primary doctor when any changes are made to your medications.

I can guarantee you that this is not the last we have heard on this topic. I will continue this discussion as data is presented.

Tags: COGENT, Plavix, Prilosec, Proton pump inhibitors
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Is Your Medicine Making You Sick to your Stomach?

Gastrointestinal side effects such as reflux and bleeding are common in patients who take aspirin and Plavix. As I have written in other blogs, the effect of aspirin is local and systemic so that enteric coated aspirin does not lessen this risk. The importance of the drugs in preventing sudden coronary stent thrombosis led to the guideline recommendation that proton pump inhibitors be given along with aspirin and Plavix to lessen the risk.

Proton pump inhibitors such as Nexium and Protonix are drugs used to decrease the amount of acid in the stomach leading to a significant reduction in ulcers and reflux. They are used along with another class of drugs called H2 antagonists which are Zantac, Pepcid and Tagamet.

On May 6, 2009, a study was released at the Society for Cardiovascular Angiography and Interventions from researchers at Medco, a large pharmaceutical distributor. The study looked at the data from 16,690 patients and their conclusions were that instead of lowering the risk of major adverse cardiovascular events, this combination of drugs increased the risk from 17.9% to 25.1 %. Their data showed that all PPI’s were the same as far as risk of events.

As I have written before, this is the wonder and frustration of medicine. How can something which appears so logical be so wrong? Is it wrong? Why is it wrong? Researchers went to work to discover the problem. It seems that these drugs share a metabolic enzyme pathway and much like cars on a busy street, not all the traffic can travel at the same time. As Plavix needs to be metabolized, this interferes with the levels of the active drug, which in turn lessens the drug’s effectiveness.

But is it true? The Principle-TIMI 44 trial examined this problem and the study was released on line before publication. They found that no association was found between PPI use and increased risk for major cardiovascular events. This study used twice the normal dose of Plavix. In a similar study using twice the dose of Plavix (150mg a day), the PACA trial (Proton Pump Inhibitors and Clopidogrel Association) found that Protonix was better than Prilosec in preserving the necessary effect of Plavix.

What to do? I am recommending to my patients that if they must take these drugs they should increase the dose of Plavix. A better choice is probably to use the H2 blockers instead of these drugs for prophylaxis of GI bleeding. If PPI’s must be used, Protonix may be the best choice in the class. More information will be presented at the American Heart Association meeting in November. Individuals who are on these combinations should discuss this with their cardiologists.

Tags: aspirin, Gastrointestinal side effects, H2 antagonists, Plavix, Proton pump inhibitors, reflux, Society for Cardiovascular Angiography and Interventions, ulcers
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