Clinical trials report
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Journal Article↗
Biomedical subjects
RA Harrington
Publications and source records attributed to RA Harrington.
Platelet Inhibition in Cardiovascular Disease Management: Aspirin and Beyond.
Intracoronary thrombosis is the central event in the pathophysiology of the acute coronary syndromes and of the complications of percutaneous coronary intervention. Hemostasis and thrombosis involve a complex series of interactions of both platelets and the coagulation system. Standard antithrombotic therapy for cardiovascular disease typically combines use of antiplatelet therapy with aspirin and antithrombin therapy with heparin. Ticlopidine appears to be a reasonable alternative as an antiplatelet agent in the patient who is intolerant of aspirin. The combination of ticlopidine and aspirin may be especially effective in preventing coronary events in the post-coronary stenting patient. Clopidogrel may offer incremental benefit beyond aspirin in a broad array of vascular diseases, but the cost effectiveness of such a strategy remains to be determined. Finally, potent antiplatelet therapy with platelet glycoprotein IIb/IIIa receptor inhibition clearly improves angioplasty outcomes and may have a role in the treatment of patients with acute coronary syndromes.
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Physicians' Use of Heparin Following Thrombolytic Therapy: An International Perspective.
Background: The current prevalence, timing, and route of heparin use after thrombolytic therapy for acute myocardial infarction both within and outside the United States (U.S.) have not been extensively studied. Method: An 18-item questionnaire was mailed to cardiologists and emergency medicine practitioners in the U.S. and to physicians in 5 countries considering participation in an international trial of thrombolytic therapy. Results: Almost all used some form of heparin after recombinant tissue-plasminogen activator; 8% withheld heparin after streptokinase. Non-U.S. physicians used subcutaneous heparin more frequently than did U.S. physicians (26% vs. 4%). Time to heparin initiation varied greatly. Most physicians used the activated partial thromboplastin time to monitor anticoagulation, although there was little consensus about the appropriate way to determine the efficacy of heparin therapy. Conclusions: This survey shows considerable disagreement about the preferred administration of heparin among physicians treating patients with myocardial infarction. This lack of agreement reflects uncertainty about how heparin therapy should be used. When the results of well-designed clinical trials examining the optimal dosing, timing, and monitoring of heparin therapy have been published, perhaps the clinical community can reach a consensus.
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Platelet Glycoprotein IIb/IIIa Integrin Blockade in Coronary Artery Disease: Current State of the Art.
Platelets have been shown to play an important role in the pathogenesis of atherosclerosis, acute coronary syndromes, and ischemic complications after percutaneous coronary intervention. Fibrinogen binding via platelet surface glycoprotein (GP) IIb/IIIa receptors constitutes the "final pathway" in platelet aggregation leading to thrombus formation. The GP IIb/IIIa receptor inhibitors, a new class of antiplatelet agents that have emerged in recent years, show great promise in reducing complications of coronary angioplasty and acute coronary syndromes. This review will examine the biology of platelet GP IIb/IIIa receptors, the various classes of GP IIb/IIIa receptor antagonists, the results of the latest clinical trials, and their implications in current clinical practice.
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Adjunctive Antiplatelet Therapy in Acute Myocardial Infarction: The Road to Improved Infarct-Related Artery Patency.
A direct relationship exists between infarct artery patency and survival in patients with acute myocardial infarction. Currently available thrombolytic regimens produce 90 minute patency rates on the order of 80%. Preliminary trials suggest that adjunctive anti-platelet therapy with glycoprotein IIb/IIIa inhibitors, in conjunction with thrombolytic therapy, may significantly improve 90 minute infarct related artery patency and thereby survival, in patients with acute myocardial infarction.
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Randomized, Placebo-Controlled Study of Lamifiban with Thrombolytic Therapy for the Treatment of Acute Myocardial Infarction: Rationale and Design for the Platelet Aggregation Receptor Antagonist Dose Investigation and Reperfusion Gain in Myocardial Infarction (PARADIGM) Study.
The benefits of thrombolytic therapy in the treatment of acute myocardial infarction are incontrovertible. Large-scale studies combining angiographic and clinical end-points have demonstrated a perfusion-mortality relationship, with the highest survival rate among patients with early restoration of TIMI grade 3 coronary arterial flow. Despite advances in thrombolytic strategies, a substantial number of patients fail to rapidly achieve and maintain adequate coronary perfusion with thrombolysis. Conjunctive therapy with aspirin has proven useful in thrombolytic regimens, likely countering the heightened platelet activity central to acute coronary syndromes. The antiplatelet effect of aspirin is relatively weak compared with that of glycoprotein IIb/IIIa platelet receptor antagonists, which block the final common pathway of platelet aggregation. Lamifiban is a nonpeptide glycoprotein IIb/IIIa receptor antagonist. In early experimental studies, Lamifiban in combination with thrombolytic therapy has been shown to effectively restore coronary arterial patency, and phase I and phase II data have shown its use to be safe. To determine the optimal dose with regard to safety and efficacy of Lamifiban to be used with thrombolytic therapy in a large-scale trial, a phase II study is underway. The Platelet Aggregation Receptor Antagonist Dose Investigation and Reperfusion Gain in Myocardial Infarction (PARADIGM) study is a randomized, placebo-controlled study of Lamifiban in 400 patients receiving thrombolysis as treatment for acute myocardial infarction. By studying 90-minute angiography, platelet aggregation, continuous electrocardiography, and clinical outcome in PARADIGM, important insights will be obtained to determine the optimal dose of Lamifiban for phase III study. We provide the background and rationale for the study of Lamifiban in PARADIGM and other ongoing studies in acute coronary syndromes.
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Antithrombotic Therapy during Percutaneous Coronary Intervention.
Ischemic complications of percutaneous coronary intervention occur commonly and are among the major limitations of the procedure. Both platelets and thrombin play an essential role in the response to the arterial injury that follows coronary intervention and in the pathophysiology of the ischemic complications of the procedure. Aspirin and heparin are essential treatments for the patient undergoing coronary intervention. Novel thrombin and platelet inhibitors are being developed that may be useful for improving both acute and long-term clinical outcomes of percutaneous coronary intervention.
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