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Principal Developer: J. Lam Antiplatelet Therapy BackgroundAntiplatelet agents are drugs which interfere with the ability of platelets to aggregate and form a platelet plug. As antithrombotic agents, they are most useful in clinical states due to arterial vascular disease. Available AgentsThe cheapest and most widely used agent is aspirin. Ticlopidine and clopidogrel are newer, and are recommended for patients with aspirin allergy or intolerance, and when clinical events arise despite ASA therapy. Clopidogrel is recommended over ticlopidine because it is associated with less serious side effects and provides superior benefit to aspirin in patients with vascular disease, such as stroke, myocardial infarction or peripheral arterial disease. This benefit is enhanced in patients at higher risk, such as those with hyperlipidemia, diabetes, prior coronary bypass surgery and disease in multiple vascular beds. Aspirin and clopidogrel have a synergistic effect and is recommended after an episode of unstable angina or non Q-wave myocardial infarction and in patients undergoing coronary stenting, where the combination has been shown to provide better cardiovascular protection. The use of sulfinpyrazone as antithrombotic agents either alone or in combination with other antiplatelet agents is not recommended. Aspirin, clopidogrel or extended-release dipyridamole in combination with aspirin are acceptable options for prevention of ischemic stroke. IndicationsAn overview of randomized clinical trials have shown that the risk of major vascular events (myocardial infarction, stroke and vascular death) is reduced by approximately 25% and the risk of mortality is reduced by approximately 15% in patients with atherosclerotic vascular disease at high risk. CardiacIn patients with acute myocardial infarction or unstable angina, uncoated aspirin should be given as soon as the diagnosis is made, whether or not thrombolytic therapy and/or heparin is to be administered. Aspirin is also recommended for patients with stable angina, post-angioplasty and CABG where it helps maintain patency as well as reduce the incidence of serious vascular events. Aspirin should be continued indefinitely in all patients unless there are indications for use of warfarin. (See Antithrombotic Therapy Post-MI guidelines). Clopidogrel (or ticlopidine) is an effective alternative in cases of aspirin intolerance or allergy. Clopidogrel (or ticlopidine) in addition to aspirin is recommended for at least 14 days following stent implantation; 30 days treatment should be considered for patients at high risk of stent thrombosis. Indications:Antiplatelet therapy is STRONGLY RECOMMENDED for ALL patients with the following unless contraindicated: Cardiac
Cerebrovascular
Peripheral Vascular Disease
Antiplatelet therapy MAY BE BENEFICIAL in the following: Cardiac
Cerebrovascular
Peripheral Vascular DiseaseThe use of aspirin may modify the natural history of intermittent claudication due to peripheral vascular disease. In the absense of contraindications, aspirin is recommended for patients with peripheral vascular disease for reduction of cardiovascular events (myocardial infarction and stroke). Clopidogrel appears superior to aspirin in reducing ischemic complications in patients with peripheral vascular disease. Primary PreventionAlthough aspirin has been shown to be effective in primary prevention of vascular disease, the overall benefit is small. Therefore, it is prudent to limit its use to individuals 50 years old with one additional risk factor for coronary disease (i.e. diabetes, hypertension, smoking, hyperlipidemia, sedentary lifestyle). Dosage and AdministrationThe usual antiplatelet dose of aspirin is 80-325 mg daily which is well tolerated. In individuals with cerebrovascular disease, there may be additional benefits to aspirin given in association with slow release dipyridamole, 200 mg BID, although this combination has not been shown to decrease coronary events. The recommended dose for Ticlopidine is 250 mg twice daily. Its use is rapidly fading in favor of clopidogrel. Ticlopidine or clopidogrel is recommended for patients with aspirin intolerance or allergy, and/or patients who have recurrent events despite aspirin therapy. Clopidogrel, 75 mg daily, is an effective alternative to ticlopidine, and is preferred over ticlopidine because it is associated with fewer serious side effects and does not require frequent monitoring of blood counts. Patients may be advised to discontinue clopidogrel or ticlopidine 7 days prior to elective surgery to minimize perioperative bleeding. Side EffectsThe most common side effect of aspirin is gastrointestinal intolerance which is dose related. Bleeding is a potential complication. The most common side effects of Ticlopidine are diarrhea and skin rash. Neutropenia has been reported and is usually reversible. Monitoring of the WBC is recommended every 2 weeks for the first 3 months of therapy. The most common side effect of Clopidogrel is skin rash. Neutropenia is uncommon, as infrequent as with ASA, and monitoring of the WBC is not necessary. Contraindications
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