Antiplatelet drugs. A comparative review.
Antiplatelet therapy has become a useful means of preventing acute thromboembolic artery occlusions in cardiovascular diseases. The rationale for this is an enhanced activity of circulating platelets and release of platelet-derived vasoactive mediators, probably due to endothelial dysfunction. This review discusses the current status of 4 major classes of antiplatelet compounds: (i) aspirin and related drugs active via cyclo-oxygenase product formation; (ii) thienopyridines (ticlopidine and clopidogrel); (iii) direct thrombin inhibitors (e.g. hirudin); and (iv) GPIIb/IIIa receptor antagonists [e.g. abciximab (c7E3 Fab)]. It is concluded that aspirin is the drug of choice for long term oral treatment, specifically for secondary prevention of myocardial infarction, and is also a suitable basic but not maximally efficient drug in percutaneous transluminal coronary angioplasty (PTCA) and platelet activation during clot lysis. Ticlopidine has a similar indication and may be superior to aspirin in prevention of ischaemic stroke and peripheral arterial occlusion. Direct thrombin inhibitors and glycoprotein GPIIb/IIIa receptor antagonists need further investigation in clinical trials. To date, these compounds have a higher bleeding risk and currently they are available only for short term parenteral application. They are superior to aspirin in acute platelet-dependent ischaemic syndromes, such as unstable angina, and in connection with therapeutic PTCA because of their high potency in preventing platelet-dependent reocclusion. Future developments include more selective thromboxane inhibitors, i.e. combined-mode agents; nonpeptide clot-specific thrombin inhibitors with longer lasting action and nonpeptide fibrinogen receptor antagonists.
Schrör
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Institut für Pharmakologie, Heinrich-Heine-Universität Düsseldorf, Germany.
D000244:Adenosine Diphosphate / Q000037:antagonists & inhibitors; D000818:Animals; D001241:Aspirin / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D001483:Base Sequence; D001792:Blood Platelets / Q000187:drug effects*; D016384:Consensus Sequence; D006801:Humans; D008969:Molecular Sequence Data; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D019038:Platelet Glycoprotein GPIb-IX Complex; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors; D013917:Thrombin / Q000037:antagonists & inhibitors; D013927:Thrombosis / Q000188:drug therapy; D013931:Thromboxanes / Q000037:antagonists & inhibitors*
D010975:Platelet Aggregation Inhibitors; D019038:Platelet Glycoprotein GPIb-IX Complex; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D013931:Thromboxanes; C032193:glycoprotein receptor GPIb-IX; D000244:Adenosine Diphosphate; D013917:Thrombin; D001241:Aspirin