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Aspirin and Clopidogrel

09/01/2005

Question:

1.My colleague aged 52 years had CABG in 1996. He has been taking Aspirin-150 once. Now he has been advised to switch over clopidogrel-75. Is this change of medicine necesary in order to rule out the tolerance the particular drug develops if taken for a considerable period. 2. Is mode of action and the efficacy of aspirin-150 and clopidpgrel 75 similar ? Kindly guide me the superirority of drugs in terms of efficacy and prophylaxis ?

Answer:

Platelets are a normal part of the body’s clotting system. Under normal circumstances, the platelets circulate in the blood until they come into contact with a blood vessel that has sustained some sort of damage. The damage could be related to trauma like a cut or scrape or it could be related to chronic disease like atherosclerosis. When platelets are activated they stick to the damaged area, clump up and release chemicals that induce the blood to clot. This effect is beneficial for limiting blood loss during trauma, but can cause strokes heart attacks (myocardial infarction) and other clot related ischemia when blockage of the blood vessels occurs. As we age, our blood vessels are more likely to have areas of damage that can activate the platelets. In addition, patients who have undergone coronary artery bypass graft (CABG) surgery are at high risk for future clots. Patients at risk for developing clots are typically managed with medicines that reduce the ability of the platelets to respond to damage in the blood vessels. Two of the medicines used in this capacity are aspirin and clopidogrel

Aspirin is a nonsteroidal anti-inflammatory drug (NSAID) that also inhibits platelet activation. However, aspirin works on platelets in a different manner than clopidogrel. Aspirin is US food and Drug Administration (FDA) indicated for the treatment of pain, fever, inflammation, and osteoarthritis. Aspirin is also indicated for the prevention of clots, which lead to stroke and heart attack. When used reduce platelet activity, aspirin is usually taken orally as a single daily dose of between 75 and 325mg. Side effects reported with aspirin include: excess bleeding, nausea, vomiting, heartburn, indigestion, and allergic reactions.

Clopidogrel (Plavix®) also inhibits platelet activation. Clopidogrel is normally taken orally once daily as a 75mg dose. Clopidogrel is used to reduce the incidence clot formation after a recent heart attack or stroke. It may also be used in patients with peripheral arterial disease, acute coronary syndrome, patients who have undergone or will undergo percutaneous coronary artery interventions with or without stent placement or (CABG), surgery. Clopidogrel therapy is recommended for patients who are unable to take aspirin because of an aspirin allergy or major gastrointestinal effects. Side effects reported for clopidogrel (Plavix®) include excess bleeding, abdominal pain, vomiting, heartburn, gastritis, constipation, chest pain and headache. It is important that patients taking clopidogrel (Plavix®) report any unusual bleeding to their physicians.

The Clopidogrel Versus Aspirin in Patients at Risk of Ischemic Events (CAPRIE) study was a large, randomized clinical trial that compared clopidogrel with aspirin in 19,185 patients. Patients treated with clopidogrel had an annual 5.32% risk of stroke, heart attack, or vascular death compared with 5.83% with aspirin. The actual difference between clopidogrel and aspirin at reducing cardiovascular events was shown to be minimal. There were no major differences in terms of safety between the aspirin and clopidogrel treatments.

The Seventh American College of Chest Physicians (ACCP) Conference on Antithrombotic and Thrombolytic Therapy recommend the following treatments for acute coronary syndrome (ACS) associated with coronary artery disease (CAD):

· All patients with chronic stable CAD that do not have an aspirin allergy should be placed on 75 to 325mg of aspirin therapy once daily.

· For patients in whom aspirin is contraindicated or not tolerated, clopidogrel 75 mg once daily is recommended for long-term therapy.

· Patients with stable chronic CAD with a high-risk of developing an acute heart attack may be placed on long-term therapy with clopidogrel in addition to aspirin.

“Aspirin resistance” is defined as the inability of aspirin to protect patients from vascular events. Unfortunately, the only way to really know if a patient is resistant to aspirin is when an individual experiences the next event. Since preventing additional cardiovascular events is the goal of therapy, therapy may need to be switched to clopidogrel if resistance is suspected. Aspirin resistance is more likely to occur in individuals who have had prior cardiovascular events. The increased risk could be related to damage to the heart from the previous event.

At least one large well conducted trial found no particular benefit to clopidogrel compared to aspirin. However clopidogrel is considerably more expensive than aspirin. Since aspirin and clopidogrel work in different ways to reduce platelet function, it may be possible to use the two medicines together to optimize therapy in some high risk patients. We are not able to make specific recommendations regarding which treatment is best for your colleague. His or her cardiologist is the most appropriate person to determine the appropriate treatment regimen. If your colleague has questions about his or her change in drug therapy, it should be addressed with the cardiologist.

This response was prepared in part by: Shari Scudder PharmD while she was a PharmD Candidate. Significant editing of the original text was done by Lauren Barton, and Jason Glasgow, PharmD candidates. All three were or are students at the University Of Cincinnati College Of Pharmacy.

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