Antiplatelet Agents in Cardiovascular and Cerebrovascular Diseases

Abstract

Aspirin has become a widely accepted platelet function inhibitor and is used to prevent arterial occlusions in coronary cerebral and peripheral vascular disease. The results of clinical studies with aspirin in the area of peripheral arterial occlusive disease are critically reviewed. Two thienopyridine compounds, ticlopidine and clopidogrel, have been effectively used in the prevention of myocardial infarction and stroke in several clinical trials, especially in the recently published CAPRIE-trial. Potent new platelet function inhibitors recently were developed. Intravenous treatment with abciximab, a new platelet membrane glycoprotein IIb/IIIa-inhibitor, effectively prevented coronary reocclusions in patients with high-risk coronary events. A series of promising new oral IIb/IIIainhibitors have been developed and may become effective drugs in the prevention of reocclusions in patients with peripheral vascular disease and in coronary or cerebral vascular disease.

Review of Currently Available GP IIb/IIIa Inhibitors and Their Role in Peripheral Vascular Interventions

“…Existing antiplatelet medications interfere with platelet activation mechanisms such as TXA2 in the case of aspirin, or ADP with the thienopyridines ticlopidine and clopidogrel. 5,6 These medications block only one of many activators of platelets and thus they are inherently weak and provide partial inhibition of platelet aggregation at best.…”

Use of Antiplatelet Inhibitors in Peripheral Vascular Interventions

“…Aspirin blocks only arachidonic acid metabolism and is therefore only a partial inhibitor of platelet aggregation. 3,4,15 Thienopyridines such as the oral medications ticlopidine and clopidogrel interfere with platelet membrane function by irreversibly inhibiting ADP-induced plateletfibrinogen binding and subsequent platelet-platelet interactions. Regardless of what agonists activate the platelet, the final common pathway to platelet aggregation is the GP IIb/IIIa receptor.…”

“…1,2 Aspirin primarily affects the biosynthesis of cyclic prostanoids such as thromboxane A 2 (TXA 2 ) by irreversibly inhibiting both the function of cyclooxygenase (COX-1) in platelets and the vascular synthesis of prostacyclin. 3,4 Although the efficacy of aspirin in preventing thrombotic complications during percutaneous coronary interventions (PCIs) is well established, [5][6][7][8] aspirin is a relatively weak platelet antagonist and some patients may be resistant to its effects. Other non-TXA 2 -dependent activators of platelet aggregation such as thrombin, adenosine diphosphate (ADP), and collagen 3,4 are not affected by aspirin.…”

“…3,4 Although the efficacy of aspirin in preventing thrombotic complications during percutaneous coronary interventions (PCIs) is well established, [5][6][7][8] aspirin is a relatively weak platelet antagonist and some patients may be resistant to its effects. Other non-TXA 2 -dependent activators of platelet aggregation such as thrombin, adenosine diphosphate (ADP), and collagen 3,4 are not affected by aspirin. The current general recommendation for aspirin use during PCI is an empirical dose of aspirin, 80 to 325 mg, given at least 2 hours prior to an intervention.…”

Klinische Bedeutung von Thrombozytenfunktionshemmern

“…Eine Reihe von relativ kleinen Studien hat gezeigt, daß ASS in Dosierungen von 1,5 g/Tag Reverschlüsse bei Patienten mit gefäßchirurgischen Eingriffen und schlechten Ausflußbedingungen nach der Operation verminderte und bis zu einem gewissen Grad auch neue Gefäßverschlüsse bei Patienten mit peripherer arterieller Ver-schlußkrankheit verhüten konnte (8). Vieles spricht dafür, daß eine ASS-Prophylaxe so früh wie möglich erfolgen sollte.…”