Antithrombotic Drugs:Insights f rom Cardiology

The primary purpose of this overview is to provide an update on the newer antiplatelet drugs evaluated in clinical trials and introduced in clinical practice of modern cardiology. Despite the remarkable clinical developments with the use of new antiplatelet drugs, several fundamental issues remain unresolved. Some of the observed safety/efficacy problems in major clinical trials can be directly attributed to the lack of careful phase II studies where issues such as monitoring, pharmacological profiles, and individual response variations were not considered sufficiently. Nevertheless, none of the available antiplatelet agents meet all the criteria of an ideal antiplatelet agent. Aspirin has been the standard reference agent in cardiovascular disease. However, it is a weak and nonselective antiplatelet compound and is unable to interfere substantially with the thrombogenic activity of a fresh mural thrombus of a stenosed vessel. The newer antiplatelet drug classes such as the ADP receptor blockers (ticlopidine, clopidogrel) and the platelet glycoprotein IIb/IIIa receptor inhibitors produce their therapeutic effects by distinct mechanisms which differ from aspirin. Large clinical trials have documented their efficacy in acute coronary syndromes associated with intracoronary thrombus formation. The future challenge is to evaluate long-term treatment strategies which are equally safe but distinctly more effective than aspirin, e.g. a combination therapy with aspirin and clopidogrel or oral GP IIb/IIIa receptor antagonists.