Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042373 (vascular disease)
 17,070 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mechanisms of action of currently available and newer antiplatelet agents and evidence of the efficacy of antiplatelet agents for primary and secondary prevention of coronary artery disease are reviewed. Available data do not support the widespread use of aspirin for primary prevention of cardiovascular disease. Patients over the age of 50 years with at least one additional risk factor for coronary artery disease may benefit, although possibly at an increased risk of hemorrhagic stroke. Aspirin is recommended for secondary prevention of vascular disease in patients with stable or unstable angina, clinical or laboratory evidence of coronary artery disease, history of myocardial infarction, or history of stroke or transient ischemic attack. There are no data supporting a role for dipyridamole for primary or secondary prevention of ischemic heart disease. Abciximab has been shown to reduce the risk of cardiovascular complications at 30 days after percutaneous transluminal coronary angioplasty in patients with refractory unstable angina. Studies with other glycoprotein IIb/IIIa-receptor antagonists, including eptifibatide, tirofiban, and lamifiban, have yielded promising results. Ticlopidine may be used for secondary prevention of cardiovascular disease in patients with unstable angina who are allergic to or intolerant of aspirin. Clopidogrel has been shown to be safe and effective for secondary prevention of vascular events. Aspirin has a role in secondary prevention of coronary artery disease; among patients who are allergic to or intolerant of aspirin, ticlopidine has a role in patients with unstable angina and clopidogrel has a potential role in patients with ischemic heart or vascular disease.
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PMID:Antiplatelet therapy in coronary artery disease: review and update of efficacy studies. 978 97

For the long-term prevention of thromboembolic events in patients with atherosclerotic vascular disease, aspirin is the preferred antiplatelet drug. Only clopidogrel was shown to be more effective and at least as safe than medium-dose aspirin in direct comparative large-scale trials. Aspirin inhibits the cyclooxygenase dependent pathway of platelet aggregation while ticlopidine and clopidogrel selectively bind to adenosine diphosphate (ADP) receptors on the platelet surface. Compounds which inhibit the synthesis of thromboxane synthase, block the thromboxane receptor or have the dual activity were effective in experimental thrombosis models in animals but not predictive of results in humans. Activation of the platelet glycoprotein (GPIIb/IIIa) receptor on the platelet surface is the final pathway of platelet aggregation, regardless of the initiating stimulus. Inhibitors of GPIIb/IIIa receptors include monoclonal antibodies (abciximab) against this receptor and peptidic as well as non-peptidic synthetic specific receptor blockers. Abciximab exchanges between and binds to platelets for as long as two weeks whereas synthetic GPIIb/IIIa inhibitors inhibit ex vivo platelet aggregation for only a few hours after the end of infusion but have the advantage of being also orally active. In the secondary prevention of atherothrombosis, large scale trials were successfully conducted with aspirin, dipyridamole and clopidogrel. In the first large-scale trials with GPIIb/IIIa inhibitors with abciximab was investigated. In aggregate, this class of platelet inhibitors, combined with aspirin and heparin, was shown to reduce ischaemic events in patients with high- and low-risk coronary intervention, stents, unstable angina and non-Q-wave infarction with long-term preservation of the initial benefit. With synthetic GPIIb/IIIa inhibitors there is no suppression of clinical evident restenosis 6 months after the end of treatment. With the doses presently used, bleeding occurs more often with the synthetic GPIIb/IIIa inhibitors (used for 3 days) than with abciximab (used for 12 hours) but there are no direct comparisons between these drugs.
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PMID:8th Seah Cheng Siang Memorial Lecture: new antithrombotic agents. 1057 18

Abciximab (c7E3 Fab, ReoPro) blocks GPIIb/IIIa and alphavbeta3 and inhibits thrombotic and proliferative events only in humans and non-human primates. The bivalent F(ab')2 fragment is an effective anti-thrombotic agent in canine models. In the present study, 7E3 F(ab')2 was also found to bind to rat GPIIb/IIIa (KD = 27 +/- 4 microg/mL) and alphavbeta3 (KD = 9 +/- 8 microg/mL), to block in vitro rat platelet aggregation (IC50 = 16 +/- 6 microg/mL), and to inhibit alphavbeta3-mediated microvessel sprout formation in a rat aortic ring assay. Following administration of 7E3 F(ab')2 (4 mg/kg) to rats, platelet aggregation was completely blocked for up to 6 h and thrombus formation in response to a rat abdominal aorta double crush injury was prevented. Effective chronic dosing was achieved with 6 mg/kg daily I.P. injections. In vitro mixing experiments indicated that 7E3 F(ab')2 redistributed to unlabeled platelets in 2 h. Ex vivo, 7E3 F(ab')2 was detected on platelets for up to 4 days after a single 4-mg/kg injection. These data suggest that 7E3 F(ab')2 may be a useful agent to study the effects of GPIIb/IIIa and alphavbeta3 blockade in rat models of thrombosis and vascular disease.
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PMID:7E3 F(ab')2, an effective antagonist of rat alphaIIbbeta3 and alphavbeta3, blocks in vivo thrombus formation and in vitro angiogenesis. 1137 85

The effects of the GPIIb-IIIa antagonists abciximab and MK-852 on platelet-leukocyte interactions in vitro were studied and the results compared with those obtained with a combination of aspirin, dipyridamole and AR-C69931 (Asp/Dip/AR-C). Platelet-monocyte (P/M) and platelet-neutrophil (P/N) conjugate formation increased when blood was stirred or a platelet agonist was added. Leukocyte activation also occurred as judged by expression of surface tissue factor antigen and CD11b. Abciximab and MK-852 potentiated P/M, especially when collagen was used. They also increased the amount of tissue factor on the monocytes, but not CD11b. The Asp/Dip/AR-C did not enhance P/M or tissue factor exposure. Augmented tissue factor expression on monocytes in the presence of a GPIIb-IIIa antagonist may be relevant to the increased mortality associated with trials of such antagonists when given orally in patients with vascular disease. The Asp/Dip/AR-C was superior to abciximab and MK-852 in inhibiting platelet and leukocyte function.
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PMID:The effects of GPIIb-IIIa antagonists and a combination of three other antiplatelet agents on platelet-leukocyte interactions. 1280 31

Glycoprotein (GP) IIb/IIIa inhibitors including abciximab, eptifibatide and tirofiban have been studied extensively as short-term adjuncts to short-term heparin and indefinite aspirin in patients with acute coronary syndrome or undergoing percutaneous coronary interventions on native vessels. The drugs provide a small advantage in the composite endpoint of death, myocardial infarction, and need for revascularization at 30 days (1-2% of treated patients) at the expense of an increase in major and potentially fatal bleeding complications (1% of treated patients over heparin plus aspirin alone). Highest-risk patients appear to benefit the most; clopidogrel should also be considered in these patients. Patients undergoing percutaneous interventions on bypass grafts do not benefit. Whether one GP IIb/IIIa inhibitor is superior to another is incompletely clarified. Abciximab causes severe immune-mediated thrombocytopenia (<20,000/microl) in 0.7% of cases; this is more often than eptifibatide or tirofiban (0.2%). Pseudothrombocytopenia should be differentiated. Effective use of GP IIb/IIIa inhibitors for acute coronary syndrome and percutaneous coronary interventions requires discerning clinical judgment. The value of GP IIb/IIIa inhibitors is not established in other forms of vascular disease.
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PMID:Platelet glycoprotein IIb/IIIa inhibitors. 1517 58