Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The influence of a 4-weeks therapy with 500 mg ticlopidine daily on platelet function parameters was examined in 10 male healthy volunteers aged 20-33 years in order to extend the knowledge on the antiplatelet activity of this substance. Ticlopidine significantly (p less than 0.01) affected ex-vivo platelet aggregation induced by ADP and increased platelet sensitivity to the antiaggregatory action of PGI2. Generation of TXB2 from endogenous substrate during spontaneous clotting of blood (serum-TXB2), conversion of exogenous radiolabelled arachidonic acid into TXB2 and MDA-formation in isolated platelets were unaffected by the treatment. The TXB2-level in plasma of volunteers, however, was decreased, after administration of the drug. The diminished alpha-granule content liberation (beta-thromboglobulin: p less than 0.01; PDGF: p less than 0.01; PF4 not significant) indicates that ticlopidine induces a decrease in platelet activity. The beneficial effect on release reaction is not associated with a decrease in TXA2-formation. Our results demonstrate that ticlopidine inhibits platelet activity, especially the PDGF-release. These results confirm the value of this drug in the prevention of atherosclerosis and its thromboembolic complications.
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PMID:Ticlopidine and platelet function in healthy volunteers. 161 96

Aspirin (acetylsalicylic acid) is effective in reducing vascular outcome events in patients with atherosclerosis: a relative risk reduction of about 30% for stroke, 22% for stroke and death, and 15% for vascular mortality. It is probable that low and high dose aspirin are similar in efficacy. Complications are more frequent with high dose aspirin than with low doses. Four randomised trials evaluating sulfinpyrazone vs placebo, and 3 trials evaluating sulfinpyrazone vs aspirin, showed more cerebrovascular events in the sulfinpyrazone group than in the aspirin and placebo groups. One small trial comparing dipyridamole with placebo in patients with cerebrovascular disease found no difference between the 2 groups in outcome. No other studies have compared dipyridamole alone with placebo or aspirin. The European Stroke Prevention Study II is currently in progress and is comparing dipyridamole + aspirin, dipyridamole, aspirin, and placebo. In the first year, the Ticlopidine Aspirin Stroke Study (TASS) showed a 42% risk reduction for stroke and death using the efficacy analysis and a 47% risk reduction for stroke and stroke death. Ticlopidine was more effective than aspirin in reducing stroke in both males and females. Apart from a reversible severe neutropenia in 0.86% of patients, ticlopidine-related adverse effects were relatively benign and reversible. The Canadian-American Ticlopidine Study (CATS) compared ticlopidine with placebo in patients with completed major strokes. The cumulative event rates for the primary outcome events of stroke, myocardial infarction and vascular death, using the efficacy approach, show clear evidence of separation almost immediately after randomisation, consistent with a constant risk reduction of about 30% in the ticlopidine group. These data provide strong evidence that ticlopidine conveys a clinically important reduction in the risk of thromboembolic events in patients with a history of completed thromboembolic stroke. In conclusion, aspirin is effective in preventing atherothrombotic morbidity and mortality. It reduces the overall vascular event rate by about 25%. Sulfinpyrazone and dipyridamole appear to add nothing important over aspirin alone. Ticlopidine is more effective than aspirin in preventing stroke. The modest, reversible risk of neutropenia, affecting less than 1% of patients, makes the benefit: risk ratio a reasonable one.
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PMID:Antiplatelet therapy in the prevention of stroke. 172 15

Prophylactic therapy with antiplatelet drugs aims to improve both the general prognosis of patients and the local progression of peripheral arterial disease. A recent meta-analysis of 28 trials revealed that the proportional risk reduction in serious vascular events is similar to that in cardio- and cerebrovascular disease. A decreased incidence of vascular complications was also found in a meta-analysis of 4 trials with ticlopidine, and a recent Swedish study [Swedish Ticlopidine Multicentre Study (STIMS)] confirmed that long term ticlopidine reduces both mortality and cardio- and cerebrovascular morbidity. There is also evidence that aspirin (acetylsalicylic acid) and ticlopidine retard progression of atherosclerosis and the occurrence of its thrombotic complications, in patients with arterial disease of the legs. Meta-analysis has recently indicated that antiplatelet agents reduce the incidence of graft occlusion in arterial surgery. These drugs are also traditionally prescribed after percutaneous revascularisation procedures. The efficacy of antiplatelet therapy in patients with peripheral arterial disease emphasises the role of platelets in this condition.
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PMID:Prophylactic antiplatelet therapy in peripheral arterial disease. 172 16

Antiplatelet agents are indicated in the prophylactic treatment of certain thromboses, and in particular those due to a complication of atherosclerosis. Acetylsalicylic acid is the best-known, the most commonly used and, probably, the currently most effective agent. The dosage remains controversial; yet, a mean dose of 300 mg daily appears to be recommended nowadays. Ticlopidine and, to a lesser extent, dipyridamole can also be used for this treatment. However numerous contra-indications, such as haemorragic diathesis, surgery and gastric ulcers tend to limit their use. As regards the combination of antiplatelet agents, clinical studies do not show superior efficacy as compared with acetylsalicyclic acid alone.
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PMID:[Platelet antiaggregants]. 179 15

The effects of 10 days' treatment with 500 mg/day ticlopidine on the filterability of red blood cells in suspension and on the microviscosity of the red blood cell membrane was evaluated in 11 patients with vascular atherosclerosis. The results show ticlopidine to be effective in influencing the rheological measures of red cell filterability and membrane microviscosity: filterability was increased and microviscosity was decreased. Ticlopidine also decreased the extent of fluorescence polarization. These results are discussed regarding possible mechanisms of action of ticlopidine.
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PMID:Red cell filterability and erythrocyte membrane microviscosity during ticlopidine treatment. 234 Sep 48

The influence of the platelet inhibitory drug Ticlopidine (T) (500 mg daily) on lipoprotein metabolism was investigated in a double-blind placebo-controlled study of 38 middle-aged men with incapacitating stable angina pectoris. The concentrations of cholesterol (C), phospholipid (PL) and triglyceride (TG) in plasma, and very low density (VLDL), low density (LDL) and high density lipoprotein (HDL) fractions were measured before and after 4 and 8 weeks of treatment. After 8 weeks of T treatment the levels of C, PL and TG were increased by 14%, 15% and 30%, respectively. These elevations were confined to the atherogenic VLDL and LDL fractions. The LDL level showed a continuous increase during the study. There were no changes in the HDL fraction. The present findings emphasize the necessity to investigate several risk factors in all attempts of prevention of atherosclerotic disease. Before and during long-term treatment with T monitoring of plasma lipoprotein levels are recommended.
Atherosclerosis 1986 Mar
PMID:Influence on lipoprotein metabolism of the platelet inhibitory drug ticlopidine. 351 63

The study was carried out in order to evaluate if Ticlopidine induces lipid metabolism changes. Twenty seven healthy subjects were studied, 14 with placebo and 13 with Ticlopidine treatment (500 mg/day), for 30 days. Total cholesterol, HDL cholesterol, triglycerides, apolipoproteins A and B were evaluated before and after treatment. No significant changes of the blood lipid parameters were observed.
Atherosclerosis 1985 Dec
PMID:Blood lipid profile in healthy subjects treated with ticlopidine. 409 84

Platelet survival times were measured twice within 6 months using autologous 111-Indium-labelled platelets in 13 male patients diagnosed as stable intermittent claudicants. Linear, exponential, weighted mean and gamma function (multiple-hit) analyses were carried out on the data. Of these methods, exact mathematical models such as linear and exponential are unsuitable for the comparison of curves which may alter with treatment or disease progression. Weighted mean platelet survival correlated (r = 0.96) with platelet survival calculated by the precision reference method of analysis, gamma function. Statistics were expressed from gamma function analyses unless otherwise stated. Severity of claudication was measured by doppler; the ratio of brachial to mean ankle pressures was directly related to platelet survival (r = 0.84). In 7 patients, where duration of claudication was greater than 5 years, platelet survival was significantly reduced (P less than 0.02) compared with 6 newly diagnosed claudicants of less than 18 months duration. Six randomly selected patients were treated with 250 mg b.d. ticlopidine during one of the study periods. Ticlopidine significantly increased platelet survival (P less than 0.02) in all patients irrespective of disease duration or severity. The involvement of platelets in atherosclerosis observed in these claudicants, can be reduced by therapy with ticlopidine, however, the lack of clinical improvement following long-term drug treatment only confirms the platelet's secondary role in this disabling disease.
Atherosclerosis 1984 Feb
PMID:Platelet survival, atherosclerotic intermittent claudication and ticlopidine. 671 68

Fifty-one men with atherosclerotic intermittent claudication and haemorheological abnormalities completed a double-blind, one-year randomised trial of Ticlopidine (500 mg/day), a new antiplatelet agent. Ticlopidine caused significant inhibition of platelet aggregation but did not fully correct abnormalities of coagulation, viscosity, and fibrinolysis. There was no significant improvement in walking ability, Doppler ankle-pressure indices, or calf blood flow. Sustained platelet inhibition for 12 months was insufficient to correct the prothrombotic abnormality of extensive atherosclerosis.
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PMID:Platelet inhibition with Ticlopidine in atherosclerotic intermittent claudication. 704 75

Twelve patients with varying degrees of peripheral atherosclerotic disease were given an antiaggregatory drug, ticlopidine [5-(6-chlorobenzyl)-4,5,6,7-tetrahydrothieno-(3,2-C)-pyridine HCl] in a single blind trial for one or four months and the effects on platelet aggregation, blood coagulation, marcro- and micro-circulation and walking distance were studied. Two patients were excluded; one because of nausea attributable to the drug, one because of lack of co-operation. No statistically significant changes in circulation parameters or walking distance were noted. No changes were observed in APT-time, thrombine- and Reptilase-clotting time, platelet counts, concentrations of fibrinogen and fibrinopeptide A in plasma or serum antithrombin activity. The mean concentration of fibrinopeptide A was slightly increased in all patients. ADP-induced aggregation was inhibited in all patients. Aggregation induced by arachidonic acid was partially inhibited but not abolished in all patients. Prostaglandin G2-induced aggregation was not altered by ticlopidine but collagen-induced aggregation was inhibited. Ticlopidine, in contrast to acetyl-salicylic acid, inhibits the primary aggregation but also seems to interfere with the release action. Treatment of larger patient groups for longer periods are necessary to determine the clinical usefulness of ticlopidine.
Atherosclerosis 1980 Aug
PMID:Antiaggregatory, physiological and clinical effects of ticlopidine in subjects with peripheral atherosclerosis. 741 66


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