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[New antithrombotic agents in coronary disease]
1Service de cardiologie, hôpital de la Pitié-Salpêtrière, Paris, France.
Insights
New antiplatelet drugs, like GP IIb/IIIa antagonists, improve outcomes for unstable angina and high-risk PTCA. While effective acutely, long-term benefits and bleeding risks require careful consideration for antithrombotic therapy.
Area of Science:
- Cardiology
- Pharmacology
- Thrombosis Research
Context:
- Unstable angina and myocardial infarction require effective antithrombotic strategies.
- Optimal aspirin dosing and aspirin resistance remain areas of investigation.
- Low molecular weight heparins show comparable or superior efficacy to unfractionated heparin.
Purpose:
- To review the efficacy of various antithrombotic agents in acute coronary syndromes.
- To evaluate the role of new antiplatelet drugs, particularly GP IIb/IIIa antagonists, in periprocedural management.
- To discuss the benefits and risks of novel antithrombotic therapies.
Summary:
- Aspirin is a cornerstone, but optimal use is debated.
- Low molecular weight heparins offer advantages over unfractionated heparin in unstable angina.
- GP IIb/IIIa antagonists (e.g., c7E3) significantly reduce ischemic events in high-risk PTCA and unstable angina, with a notable reduction in death and myocardial infarction.
- While potent, GP IIb/IIIa antagonists increase hemorrhage risk; low-dose heparin regimens may mitigate this.
- Other agents like direct antithrombins have shown negative results, but oral antiplatelet drugs hold future promise.
Impact:
- GP IIb/IIIa antagonists have demonstrated immediate and sustained benefits in reducing mortality and myocardial infarction in high-risk patients.
- The development of potent antithrombotic drugs is improving the prognosis of acute coronary syndromes.
- Further research into oral antiplatelet agents may revolutionize future treatment paradigms.
Abstract:
Aspirin is effective in, treating patients with unstable angina or myocardial infarction. However, questions remain about the optimal dose of aspirin and aspirin-resistance in subgroups of patients. Heparin also has beneficial effects mostly during the acute phase of unstable angina, but thrombolytics are effective only in acute myocardial infarction and not in unstable angina. Recently, low molecular weight heparins have proved to be as effective (FRIC trial) or more effective (ESSENCE trial) than unfractionated heparin in unstable angina. Ongoing studies (TIMI 11B) are evaluating the efficacy of a prolonged administration of low molecular weight heparin to alter the chronic process of unstable angina. The new antiplatelet drugs directed against GP IIb/IIIa receptors are now available to improve the acute results of high risk percutaneous transluminal angioplasty (PTCA). This new drug (c7E3) binds rapidly to GP IIb/IIIa and prevents fibrinogen binding to the receptor. This very potent and irreversible effect prevents platelet aggregation and decreases the incidence of acute occlusions following PTCA. especially in patients with unstable angina. The counterpart is an increased risk of hemorrhage, knowing that patients receive simultaneously aspirin and heparin. The first results of the EPILOG study also demonstrate a better outcome in elective angioplasty without significant increase of serious bleeding, thanks to a low dose heparin regimen. In contrast to thrombolytics, the GP IIb/IIIa antagonist does not increase the risk of intracranial bleeding. The results of the CAPTURE trial also confirm the clinical benefit obtained with this drug in refractory unstable angina. The reduction of death and myocardial infarction is very consistent throughout the studies performed with c7E3. The Kaplan-Meier curves of freedom of death and myocardial infarction diverge immediately after start of study medication. The acute benefits are preserved at 3 years in the EPIC trial. Similar trends were present during the acute phase with other compounds (tirofiban, integrelin), meaning that a class effect may exist but the long term results are disappointing. The results with new direct antithrombins such as hirudin, or hirulog in acute myocardial infarction or in PTCA for unstable angina are negative. The development of new potent oral antiplatelet drugs might change the treatment of acute coronary syndromes in the future. The current progress made with antithrombotic drugs should improve the prognosis of acute coronary syndromes.