Current Issues in Thrombosis Prevention with Antiplatelet Drugs

Giovanni de Gaetano, Chiara Cerletti, Elisabetta Dejana, Jos Vermylen

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

In this review, the major current problems related to the pharmacology and clinical use of antiplatelet drugs are discussed in relation to the physiopathology of the platelet-vessel wall interaction and arterial thrombus formation. Although platelet adhesion to injured vessels is a crucial step in thrombogenesis, none of the currently used antiaggregating drugs prevents this phenomenon. Why the normal endothelium does not react with platelets is not known. Thus we are unable to pharmacologically restore endothelial ‘nonthrombogenicity’ when lost by single or repeated injury. In contrast, more information is available on the mechanisms controlling and amplifying platelet activation by physiological stimuli (such as collagen and thrombin), and on their pharmacological modulation. The 3 main amplification loops involve arachidonic acid metabolism, ADP release and possibly the availability of a phospholipid platelet activating factor. These pathways are in turn activated by the phosphatidylinositol cycle. The most widely used antiaggregating drug is aspirin. It prevents the formation of arachidonic acid metabolites both in platelets and in vascular cells. The use of low-dose aspirin, thromboxane-synthase inhibitors, thromboxane receptor antagonists, epoprostenol (prostacyclin) and its stable analogues, and ticlopidine all appear to be promising pharmacological approaches, but none has so far been tested in clinical trials for thrombosis prevention. On the other hand, aspirin (in relatively large doses of 300 to 1500mg daily), sulphinpyrazone and dipyridamole have been tested alone or in combination in the secondary prevention of thromboembolic complications. Aspirin has significantly reduced both the occurrence of myocardial infarction and mortality rate in patients with unstable angina and/or previous myocardial infarction; it has also proved beneficial in cerebrovascular disease. The beneficial effect of aspirin was dose-independent. In some of these trials aspirin was combined with either dipyridamole or sulphinpyrazone. When used alone, the latter compound has reduced sudden death or thromboembolic complications in patients with myocardial infarction. It remains to be established whether antiplatelet therapy may prevent or stop the progression of atherosclerosis.

Original languageEnglish
Pages (from-to)517-549
Number of pages33
JournalDrugs
Volume31
Issue number6
DOIs
Publication statusPublished - 1986

Fingerprint

Platelet Aggregation Inhibitors
Aspirin
Platelets
Thrombosis
Blood Platelets
Sulfinpyrazone
Dipyridamole
Myocardial Infarction
Epoprostenol
Arachidonic Acid
Pharmacology
Thromboxane Receptors
Ticlopidine
Cerebrovascular Disorders
Clinical Pharmacology
Platelet Activating Factor
Thromboxanes
Unstable Angina
Platelet Activation
Metabolites

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Health, Toxicology and Mutagenesis
  • Toxicology

Cite this

Current Issues in Thrombosis Prevention with Antiplatelet Drugs. / de Gaetano, Giovanni; Cerletti, Chiara; Dejana, Elisabetta; Vermylen, Jos.

In: Drugs, Vol. 31, No. 6, 1986, p. 517-549.

Research output: Contribution to journalArticle

de Gaetano, Giovanni ; Cerletti, Chiara ; Dejana, Elisabetta ; Vermylen, Jos. / Current Issues in Thrombosis Prevention with Antiplatelet Drugs. In: Drugs. 1986 ; Vol. 31, No. 6. pp. 517-549.
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