Proton Pump Inhibitors and Plavix

To prescribe or not to prescribe

In the past few weeks, there has been much concern regarding drugs known collectively as proton pump inhibitors and the increased risk of heart attacks while taking these drugs together. In order to understand this concern, it is important to understand what these drugs do and why physicians prescribe them.

Proton pump inhibitors (also known as PPIs) are drugs prescribed by your doctor to prevent or decrease the risk of gastrointestinal bleeding. A cardiac stent is a device implanted in a blood vessel in a procedure known as an angioplasty in order to improve the blood flow in a blood vessel that supplies the heart muscle.

The risk of bleeding increases after a cardiac stent implantation due to the fact that two blood thinners (aspirin and plavix) are prescribed in order to reduce the risk of a condition known as stent thrombosis. Stent thrombosis is a very serious and possibly fatal condition where a blood clot suddenly develops within a stent and shuts down the blood supply in the stented blood vessel. In a study known as the PAMI trial, it was shown that gastrointestinal bleeding after a heart attack increased the length of hospitalization increased the risk of mortality (or the risk of dying) not only during the hospitalization but also at six months.

Several studies have been published recently regarding the interaction of plavix with PPIs. The OCLA study (Omeprazole CLopidogrel Aspirin) published in January 2008 studied the interaction of omeprazole and plavix in one hundred twenty-four patients. They found that omeprazole reduced the effectiveness of plavix and suggested that further studies were needed to study the combined effects of the two drugs. The CREDO study, on the other hand, found no increase in cardiac events in patients taking a PPI and plavix. There was a large study by Juurlink published in the Canadian Medical Association Journal in 2009, which included 13,636 patients who had suffered a previous heart attack, and it reviewed the risk of a subsequent heart attack with various PPIs.

This study found that not only did the PPIs in general increased the risk of a second heart attack; but also found that not all PPI are the same when it came to increasing the risk of another heart attack. Pantoprazole (also known as Protonix) did not increase the risk of a second heart attack while the other PPIs had a significant increase in readmission to the hospital for a heart attack. Recently a preliminary report from the Clopidogrel Medco Outcomes Study revealed that there was an increased risk of a major cardiovascular event (such a as heart attack) with one year in patients who received a cardiac stent, who were taking both plavix and a PPI, and who did not have a previous cardiac event.

In patients who had a previous cardiac event, the risk of another major cardiac event within the year was even higher. This study also found that in patients taking plavix and a PPI, there was a 50% increase in the combined risk of hospitalization for heart attack, stroke, unstable angina, or repeat revascularization. Furthermore there was a 70% increase in the risk of heart attack or unstable angina, a 48% increase in the risk of stroke or stroke-like symptoms and a 35% increase in the need for a repeat coronary procedure. This has been the largest study to date and included 16,690 patients. Finally the Journal of the American Medical Association recently published a study of 8205 patients in the Veteran’s healthcare system, which found that patients who were prescribed a PPI and plavix had a higher risk of death and/or admission for a cardiovascular event than patients who were only prescribed a PPI alone.

So what is the bottom line? While this article cannot substitute a discussion between you and your doctor or provide medical advice for your medical condition, there are a few things to know. First, never stop or start any medication without talking to your doctor. Remember to always consult a physician regarding any concerns or questions that you may have since the information provided in this article may not be applicable to your medical condition. Second, the benefits of taking a proton pump inhibitor probably outweigh the risk of the interaction between PPI and plavix in patients who are at high risk of gastrointestinal bleeding.

High-risk bleeding factors include patients with a history of a complicated ulcer, a history of a non-bleeding ulcer, history of gastrointestinal bleeding, or a patient taking additional blood thinners such as coumadin. Proton pump inhibitors may also be considered in patients with multiple additional risk factors such as age greater than 60 years, patients on corticosteroids such as prednisone, and patients with symptoms of gastro esophageal reflux disease. Third, if a PPI is needed, pantoprazole is probably safer than the other PPIs, though there are conflicting reports on this drug as well.

Some physicians have suggested using a older class of drugs known as H2-blockers such as pepcid/zantac/tagamet; but these drugs may not be as effective in preventing gastrointestinal bleeding. Finally, physicians should have a better understanding of the safety of clopidogrel plus aspirin with or without omeprazole once the COGENT-I trial is completed.

Arsalan Shahzad, MD
CVC of Texas
506 Graham St.
Tomball, TX 77375
(281) 351-8500