Antiplatelet therapy in the prevention of ischemic vascular events: Literature review and evidence-based guidelines for drug selection

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Abstract
Background: New antiplatelet drugs are being developed and many clinical trials evaluating the benefits of antiplatelet drugs for the secondary prevention of ischemic events in patients with atherosclerotic vascular disease have been performed. Hypothesis: An updated systematic review and evidence‐based guidelines for the appropriate selection of antiplatelet drugs may be beneficial to physicians and healthcare organizations attempting to create or update current clinical practice guidelines or clinical pathways aimed at caring for these patients. Methods: (1) A systematic review of the recent literature on the relative efficacy and safety of aspirin, ticlopidine, and clopidogrel was undertaken; (2) an evidence‐based, expert panel approach using a modified Delphi technique to create explicit guidelines for prescribing antiplatelet therapy was instituted; and (3) the recommendations of an expert panel were summarized. Results: Consensus guidelines were developed for the utilization of aspirin, ticlopidine, or clopidogrel for the prevention of ischemic events in patients with manifestations of atherosclerotic vascular disease (prior myocardial infarction, prior ischemic stroke, or established peripheral arterial disease) who are at increased risk for recurrent ischemic events. Based on efficacy and safety, clopidogrel was recommended as the drug of choice for patients with established peripheral arterial disease; aspirin or clopidogrel should be considered in patients with prior myocardial infarction (with clopidogrel favored for patients who have had a recurrent event while on aspirin or in whom aspirin is contraindicated); aspirin or clopidogrel should be considered as first‐line treatment in patients with prior ischemic (nonhemorrhagic) stroke‐however, clopidogrel is the favored drug in patients in whom other antiplatelet drugs are either contraindicated or who have had recurrent events while on therapy. Conclusions: Myocardial infarction, ischemic stroke, and peripheral arterial disease are all clinical manifestations of the same underlying disease process (atherosclerosis), with thrombus formation on the disrupted atherosclerotic plaque (atherothrombosis) being a common precipitating factor of ischemic events in patients suffering from these disorders. An evidence‐based approach was used to develop a practice guideline, based on available published evidence, for the appropriate utilization of antiplatelet agents (aspirin, ticlopidine, or clopidogrel). These guidelines may be of use to multidisciplinary teams wishing to create or update clinical guidelines or clinical pathways which address the care of patients with atherosclerotic vascular disease. New antiplatelet agents such as clopidogrel may be more effective and associated with lower risk of selected adverse effects (such as gastrointestinal distress, gastrointestinal hemorrhage, and neutropenia) than those previously used to prevent thrombus formation in the setting of atherosclerotic arterial disease. Combination antiplatelet therapy is being evaluated as an option for those patients who experience recurrent events on a single antiplatelet agent.