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Aspirin: Cost, Convenience, Efficacy and Safety

11/22/2005

Question:

On 25-07-2005 I saw a question regarding Right High Parietal Lacunar infarct on an MRI of the brain and the internist suggested Aspirin 162.5. I had a right high prietal lacunar infarction with Mild cerebral atrophy. An MRI was done, since I had vertigo, but, in fact, the MRI finding is accidental. It turned out to be benign postural vertigo. The lacunar infarct was silent without any symptoms and had an MRI not been conducted, I would probably not have come across the finding. My doctor gave me Aspirin 150 because I am a 50 year old male who is hypertensive. During recent Upper GI Endocopy, I was found to have MILD ANTRAL GASTRITIS : DUODENITIS IN BULB : NO ACTIVE ULCER SEEN. Is it necessary to stop aspirin and start clopedogrel? My internist says I need to take clopedogrel whereas my Gasestrientrologist says I can take Aspirin 150. Please help me. I do not seek any diagnosis but your suggestion.

Answer:

Please note: We have received several VERY similar questions recently.  This answer is meant to cover all of them.

The American College of Chest Physicians currently considers three drug regimens as drugs of choice for preventing strokes.  These include Aspirin 75-325 mg daily, Clopidogrel (Plavix®) 75mg daily and  a combination of aspirin 25 and  extended release dipyridamole 200mg (Aggrenox®) taken twice daily.  All three drug regimens work by preventing platelets in the blood from binding together. This platelet aggregation is the first step in the formation of blood clots.  Blood clots are responsible for most strokes, including lacunar infarcts.

While some controversy exists, most clinicians are likely to choose aspirin first because it works well in a single daily dose and it is by far the least expensive. In addition to these benefits, aspirin is the anti-platelet drug that clinicians have had the most experience using. The use of aspirin is limited by its propensity to cause irritation, bleeding and in some cases ulcers in the stomach.  Your physician has attempted to manage your mild gastric irritation by adding Protonix®. pantoprazole (pan toe' pra zole) and domperidone.  Pantoprazole is a medicine used to treat peptic ulcers and gastro-esophageal reflux.  Domperidone increases stomach motility and reduces nausea and vomiting caused by other medicines.  Domperidone is not available in the United States, but appears to be similar to metoclopramide.  The addition of pantoprazole and domperidone to control the side effects of aspirin adds cost and complexity to your drug regimen. These factors add weight to the argument for switching to clopidogrel.  Taking your aspirin with food and lowering your daily aspirin dose to 75 mg are other options.  Aspirin begins working to prevent platelet aggregation within one hour of taking a dose.

 In patients who cannot tolerate aspirin clopidogrel is a good choice.  Clopidogrel is also taken once daily.  Clopidogrel can cause diarrhea and rash.  Patients stop taking clopidogrel due to side effects about as frequently as patients taking aspirin.       Clopidogrel takes 3-7 days to reach its full effect so you would need to continue the aspirin for several days after beginning the new medicine.

The newest anti-platelet drug is a combination of immediate release aspirin (25mg) and extended release dipyridamole (200mg). This product is sold under the brand name of Aggrenox® in the United States. The combination product has been around for at least five years, but both of the component medicines have been around for a long time.  Aggrenox® must be taken two times daily and costs about the same as clopidogrel.   It has been compared in a number of clinical trials, but the recent European Stroke Prevention Study (ESPS-2) did the most to demonstrate the ability of the combination to reduce the occurrence of non-fatal second strokes.   Evidence regarding the ability of the combination to prevent non-fatal heart attacks or death due to vascular accidents is less convincing.  For this reason, some clinicians feel that the new aspirin/dipyridamole combination should be considered a second line agent.  However it is an option for patients that cannot tolerate higher doses of aspirin.  In ESPS-2 about 25% of patients stopped taking the medicine early due to headaches and gastrointestinal complaints.   

A paper published November 5th 2005 reports the results of a large trial in which short term (around 15 days) use of a combination of clopidogrel 75 mg and aspirin 162 mg was compared to aspirin alone to prevent a second clot related event in patients after a heart attack.  In this study the combination was significantly better than aspirin alone.  The percentage of patients discontinuing the treatment for any reason was the same in both groups.  The study does not evaluate long term use of the combination nor does it look at secondary prevention in stroke patients.  In an earlier study in stroke patients the combination produced no clear reduction in second strokes and a significant increase in the risk of serious adverse events.  At this point we do not recommend this combination for long term use in stroke patients.

Whether you should continue aspirin, perhaps at a lower dose, or switch to one of the other anti-platelet regimens requires a consideration of cost, convenience, efficacy and safety during long term use. Switching from aspirin to either clopidogrel or the aspirin/dipyridamole combination will add about $100 dollars US per month to the cost of your medical care.  However, the addition of two drugs to control the gastrointestinal side effects of aspirin adds weight to the argument for clopidogrel on the basis of cost and convenience.

 In addition to anti-platelet drugs, a stroke prevention plan should include smoking cessation, and control of high blood pressure, high cholesterol and diabetes.  Your doctors and a pharmacist who knows you can guide you towards a healthier lifestyle. 

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Response by:

Robert James Goetz, PharmD, DABAT
Assistant Professor of Pharmacy Practice
College of Medicine
University of Cincinnati