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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Aspirin is the most widely employed antithrombotic agent in use today and has a proven role in the prevention and acute management of atherosclerosis-associated arterial thrombotic events. More recently developed antiplatelet agents have been found to have specific prophylactic roles associated with percutaneous coronary intervention and other clinical settings. This article outlines pharmacologic considerations and current clinical knowledge relevant to the use of aspirin, ticlopidine, clopidogrel, and the GPIIbIIIa antagonists in the management of thrombotic disorders.
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PMID:Antiplatelet therapy. Aspirin, ticlopidine/clopidogrel, and anti-integrin agents. 992 34

Aspirin is the most widely prescribed agent to reduce the platelet-mediated contributions to atherosclerosis, coronary thrombosis and restenosis after angioplasty. While aspirin treatment has led to significant reductions in morbidity and mortality in many clinical trials, there are several scenarios in which aspirin may fail to provide a full antithrombotic benefit. The cyclic flow model of experimental coronary thrombosis suggests that elevations of plasma catecholamines, high shear forces acting on the platelets in the stenosed lumen and the presence of multiple, input stimuli can activate platelets through different mechanisms that may lead to thrombosis despite aspirin therapy. Aspirin therapy is limited because it only blocks some of the input stimuli, leaving aspirin-independent pathways through which coronary thrombosis can be precipitated. These include thrombin and thrombogenic arterial wall substrates such as tissue factor. New agents that block the adenosine diphosphate (ADP) receptor, or regulate platelet free cytosolic calcium, such as direct nitric oxide donors, may be more potent overall than aspirin. Agents that block the platelet integrin GPIIb-IIIa receptor inhibit the binding of fibrinogen to platelets regardless of which input stimuli activate the platelet and, thus, as demonstrated in the cyclic flow model, would be much more potent than aspirin as an antithrombotic agent. The cyclic flow model has been useful in predicting which agents are likely to be of benefit in clinical trials.
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PMID:A perspective on the potential problems with aspirin as an antithrombotic agent: a comparison of studies in an animal model with clinical trials. 997 6

Ischemic stroke, myocardial infarction and peripheral arterial disease are different clinical manifestations commonly due to the same underlying disease, i.e. atherosclerosis with subsequent thrombosis/embolism (atherothrombosis). Many clinical trials of secondary prevention after stroke or TIA have evaluated the benefit of long-term use of antiplatelet drugs in reducing the risk of subsequent vascular events. Aspirin and triclopidine have been shown to be effective in placebo-controlled studies for the composite outcome of stroke, myocardial infarction, or vascular death. Contrasting with these benefits, there were potentially serious, though rare, adverse effects. These considerations certainly justify the development of new antiplatelet agents. Clopidogrel is a new ADP-receptor antagonist, with a greater activity in animal models of thrombosis. CAPRIE (Clopidogrel versus Aspirin in Patients at Risk of Ischemic Events) was a randomized, blinded, international trial designed to assess the relative efficacy of clopidogrel and aspirin in reducing the risk of the outcome cluster of ischemic stroke, myocardial infarction, or vascular death, as well as to assess their relative safety. 19,185 patients were recruited. The intention-to-treat analysis showed that the relative risk reduction was 8.7% (95% CI 0.3-16.5, p = 0.043) in favor of clopidogrel from an overall annual event rate of ischemic stroke, myocardial infarction, or vascular death, ranging from 5.83% in the aspirin group to 5.33% in the clopidogrel group. The percentage of adverse events reported was higher in the aspirin group for all categories except rash, diarrhea, and abnormal liver function. It seems likely that clopidogrel will replace ticlopidine for stroke prevention, because of its better safety profile, and comparable efficacy. Clopidogrel probably will not replace aspirin as the first line therapy for many clinicians because of its higher cost and lack of widespread experience. However, other clinicians have already decided that they will use clopidogrel as first choice, because of the significant advantage over aspirin demonstrated in the CAPRIE study.
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PMID:Clopidogrel for cerebrovascular prevention. 1047 7

Antiplatelet drugs have been demonstrated to reduce the incidence of myocardial infarction (MI), stroke or vascular death in patients with vascular disease. There are no data suggesting that antiplatelet therapy acts differently in older people than in younger people and recommendations based on randomised clinical trials are probably generalisable to older people. Aspirin (acetylsalicylic acid) has been shown to reduce the incidence of non-fatal MI, nonfatal stroke and vascular death in patients with acute MI, a previous MI, angina pectoris or peripheral occlusive arterial disease (POAD), and to reduce cardiovascular morbidity and mortality in patients with a prior ischaemic stroke or transient ischaemic attack (TIA). It has also been shown to reduce the incidence of thrombus formation after coronary artery bypass graft surgery and percutaneous transluminal angioplasty, and in patients with atrial fibrillation and heart valve replacements. Deep vein thrombosis and pulmonary embolism after surgery are also prevented by aspirin. The available data allows the following recommendations to be made. Aspirin 160 to 325 mg daily should be administered to older men and women without contraindications to aspirin who have acute MI, prior MI, unstable or stable angina pectoris, ischaemic stroke, TIA or POAD, and continued indefinitely to reduce the risk of MI, stroke or vascular death. Aspirin should be started in patients before or immediately after revascularisation, and after heart valve replacement. Older men and women with nonvalvular atrial fibrillation who have contraindications to oral anticoagulant therapy but no contraindications to aspirin should be treated with aspirin 325 mg daily. It is reasonable to treat older men and women without contraindications to aspirin with aspirin 160 to 325 mg daily if they are at high risk for developing new coronary events. The incidence of stroke, MI or vascular death in patients after a stroke or TIA is reduced by ticlopidine. Therefore, ticlopidine 250 mg twice daily may be used in older men and women with a history of stroke or TIA who do not respond to or who cannot tolerate aspirin. Patients at high risk for coronary artery stent thrombosis benefit from combined therapy with aspirin plus ticlopidine. The annual incidence of ischaemic stroke, MI or vascular death was significantly reduced by clopidogrel in the Clopidogrel versus Aspirin in Patients at Risk of Ischemic Events (CAPRIE) trial. Therefore, clopidogrel 75 mg daily may be used in older men and women with symptomatic atherosclerosis who do not respond to or who cannot tolerate aspirin to reduce the incidence of ischaemic stroke, MI or vascular death. It should be noted that the acquisition cost for either ticlopidine or clopidogrel is considerably greater than that for aspirin. Most data indicate that the combination of aspirin and dipyridamole is not more effective than aspirin alone in preventing vascular events, and available data do not support the use of sulfinpyrazone in patients with vascular disease.
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PMID:Antiplatelet agents in the prevention of cardiovascular morbidity and mortality in older patients with vascular disease. 1049 69

Besides the optimal management of risk factors for stroke and carotid surgery, antiplatelet agents are the cornerstone for prevention of cerebral ischaemia. The aim of this overview is to determine their role in the prevention of cerebral ischaemia, from available literature. In primary prevention, the benefit of aspirin has been established only for patients with non-valvular atrial fibrillation and a low risk of cardioembolism, or as an alternative choice of warfarin, and in subjects at high risk of atherosclerosis. In secondary prevention, antiplatelet agents are effective to reduce the risk in patients with ischaemic stroke due to atherosclerosis: aspirin (50 to 1300 mg), ticlopidine (500 mg), clopidogrel (75 mg) and dipyridamole (400 mg) are effective, but the higher levels of risk reduction are obtained with clopidogrel, ticlopidine and the association aspirin--dipyridamole. Aspirin is recommended in most other causes of cerebral ischaemia, except in high risk cardiopathies when anticoagulation is possible. Other domains should still be explored: are antiplatelet agents also effective to reduce the risk of cerebral ischaemia in patients with other causes, especially lipohyalinosis of the deep perforators leading to lacunar infarcts? In daily practice, does prescription follow recommendations? Will it be possible to reproduce the results of the European Stroke Prevention Study (ESPS)2? Are antiplatelet agents other than aspirin effective in non-valvular atrial fibrillation? Are other associations of antiplatelet agents more effective than these agents alone? Finally, what will be the role of new antiplatelet agents in the future?
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PMID:[Prevention of cerebral ischemia: anti-platelet agents]. 1052 50

Oxidative stress and inflammatory processes are of major importance in atherogenesis because they stimulate oxidized LDL (Ox-LDL)-induced macrophage cholesterol accumulation and foam cell formation, the hallmark of early atherosclerosis. Under oxidative stress, both blood monocytes and plasma lipoproteins invade the arterial wall, where they are exposed to atherogenic modifications. Oxidative stress stimulates endothelial secretion of monocyte chemoattractant protein 1 (MCP-1) and of macrophage colony stimulating factor (M-CSF), leading to monocyte adhesion and differentiation, respectively. LDL binds to extracellular matrix (ECM secreted by endothelial cells, smooth muscle cells and macrophages) proteoglycans, in a process that contributes to the enhanced susceptibility of the lipoprotein to oxidation by arterial wall macrophages. ECM-retained Ox-LDL is taken up by activated macrophages via their scavenger receptors. This leads to cellular cholesterol accumulation and enhanced atherogenesis. Protection of LDL against oxidation by antioxidants that can act directly on the LDL, or indirectly on the cellular oxidative machinery, or conversion of Ox-LDL to a non-atherogenic particle by HDL-associated paraoxonase (PON-1), can contribute to attenuation of atherosclerosis.
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PMID:Oxidized low density lipoprotein: atherogenic and proinflammatory characteristics during macrophage foam cell formation. An inhibitory role for nutritional antioxidants and serum paraoxonase. 1053 26

The role of the platelet and the endothelium in the pathogenesis of atherosclerosis and subsequent ischemic events has been the subject of extensive investigation. Arterial sites where endothelial function is severely impaired are often the sites of atheroma development. Lesion evolution impairs endothelial function, leading to a self-perpetuating cycle of growth. During early lesion development, overt thrombotic events are rare. However, rupture of an advanced, necrotic plaque or intimal ulceration triggers arterial thrombosis, at which point the importance of platelet function may be seen clearly. The Antiplatelet Trialists' Collaboration meta-analysis demonstrated the benefit of antiplatelet therapy to patients with atherosclerotic disease. Aspirin is the most widely studied agent and is considered the standard of antiplatelet therapy. Newer agents that intervene at different stages of the platelet activation pathway have been developed. Clopidogrel, a new adenosine diphosphate receptor antagonist, is more effective than aspirin in reducing vascular events in patients with prior myocardial infarction, stroke, or established peripheral arterial disease. The glycoprotein IIb-IIIa antagonists such as abciximab have proven effective in the setting of active arterial thrombosis and percutaneous revascularization, but their value in secondary prevention remains unknown. All patients with atherosclerosis should be treated with an antiplatelet drug. Current evidence suggests that either aspirin or clopidogrel are appropriate first-line agents. There is urgent need for an analysis of the risk/benefit ratio in various populations and clinical settings to determine the most appropriate type and intensity of therapy for a given patient.
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PMID:Platelet-endothelial interactions in atherothrombotic disease: therapeutic implications. 1055 82

In general, aspirin is indicated to prevent thrombosis in conditions associated with high shear rates (i.e., atherosclerosis) and warfarin is indicated to prevent thrombosis in conditions associated with stasis (i.e., atrial fibrillation). While aspirin and warfarin should generally not be used together, their combined use is beneficial in selected patients (e.g., some patients with mechanical valve prostheses). Aspirin in a dose of 75-150 mg per day is indicated to prevent vascular events in patients with ischaemic heart disease and also in patients at high risk of ischaemic heart disease. All patients with atrial fibrillation should be considered for oral anticoagulant therapy, with the decision for its use based on an assessment of the balance between the risk of thromboembolism and bleeding. The recommended therapeutic INR (international normalised ratio) range in non-valvular atrial fibrillation is 2.0-3.0. Warfarin is contraindicated in pregnancy, particularly during the first trimester; however, it may still need to be used in the second and third trimesters in patients with mechanical valve prostheses.
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PMID:Warfarin or aspirin: both or others? 1056 Apr 51

Platelet active drugs are part of the antithrombotics. Their biological effect is not assessed in current practice. Their clinical efficacy has been firmly established in randomised controlled trials. Aspirin has been the most widely tested drug and is effective in various forms of coronary artery disease and in the secondary prevention after a first ischaemic stroke; in these settings, aspirin reduces the incidence of myocardial infarction, stroke and cardiac death; aspirin has been tested in various daily doses from 30 to 1300 mg: best evidence has been gathered for dosages between 75 and 300 mg; good clinical practice is to use the lowest effective dose. Ticlopidine and clopidogrel have been shown to be superior to aspirin in 2 trials where the incidence of myocardial infarction has been lowered by the new drugs; nevertheless the superiority is apparent only in patients with lower limb atherosclerosis and after stroke. The combination of dipyridamole and aspirin has been proven to be superior to aspirin in the secondary prevention of stroke in one trial contrasting with the other trials performed with other combinations of those two drugs. Glycoprotein GP IIb/IIIa antagonists have been tested in coronary angioplasty and in acute coronary syndromes and only in short intravenous administration; these drugs reduce the incidence of myocardial infarction without any effect on 6-month mortality.
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PMID:[Indications for antiplatelet medications]. 1058 93

Aspirin is the cornerstone of therapy for unstable angina and acute myocardial infarction and the foundation on which other therapies are added, both in the short term and the long term. Yet, despite clear data, aspirin is woefully underused or is often used late. Prompt administration of aspirin could save thousands of lives each year. Ticlopidine and clopidogrel have a synergistic effect when used with aspirin, and can also have a role in treating patients who are aspirin-resistant or have diffuse atherosclerosis.
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PMID:Aspirin, ticlopidine, and clopidogrel in acute coronary syndromes: underused treatments could save thousands of lives. 1059 66


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