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Commencing Volume 19, Issue 1, MedReviews has ceased the publication of this journal. Reviews in Cardiovascular Medicine will continue to be published by IMRPress, Ltd. (www.imrpress.com)

Volume 7, Supplement 3, 2006

Volume 7, Supplement 3, 2006

Table of Contents

Platelet Protagonist/Antagonist: Understanding the Distinguishing Characteristics of Anticoagulants Anticoagulation in the Cath Lab
Clinical coagulation laboratory tests do not accurately reflect hemostasis and thrombosis in vivo. Thrombin generation in vivo occurs in 3 overlapping phases: initiation, priming, and propagation. During initiation, injury to the vessel wall exposes the cells to tissue factors, which lead to the production of small amounts of thrombin. During priming, the thrombin that is generated initially binds to platelets and activates them through protease-activated receptors. During the propagation phase, factor X is activated by the factor IXa/VIIIa complex that is assembled on the activated platelet surface. Subsequent formation of factor Xa/Va complexes on the platelet surface leads to a burst of thrombin and fibrin formation. Pharmacologic concentrations of a direct thrombin inhibitor, bivalirudin, inhibit thrombin-induced activation of platelets to a greater extent than pharmacologic concentrations of unfractionated heparin. [Rev Cardiovasc Med. 2006;7(suppl 3):S3-S11]
Bleeding as a Predictor of Mortality Risk Anticoagulation in the Cath Lab
The increased rate of bleeding during and after cardiac procedures is a concern. The best strategy is prevention of bleeding complications with anticoagulant therapy that provides an adequate anti-thrombotic effect while reducing bleeding. The independent relationship between bleeding and blood transfusion and mortality among patients with coronary artery disease is reviewed. Findings suggest that in the modern era of percutaneous coronary intervention, prevention of bleeding should be a goal of therapy, which can be achieved while preserving the low rate of ischemic complications. [Rev Cardiovasc Med. 2006;7(suppl 3):S12-S18]
Practical Guidelines for the Use of Anticoagulants in the Catheterization Laboratory Anticoagulation in the Cath Lab
Optimal treatment of patients during percutaneous coronary interventions (PCIs) is constantly changing as clinical trials provide new and clinically relevant information. Clinicians need to be aware of this information to incorporate these new strategies into clinical practice, leading to improvements in the care of patients. The direct thrombin inhibitor, bivalirudin, will play an increasingly important role as the primary anticoagulant for PCIs because it meets the criteria as a safer, cost-effective, and convenient agent in a spectrum of clinical scenarios. This article will provide practical guidelines to assist the interventional cardiologist to prepare his or her patient for PCI and will focus on some of the more common and more difficult patient cohorts, in particular those patients with chronic kidney disease as well as the elderly, 2 of the fastest growing groups of patients undergoing PCI. [Rev Cardiovasc Med. 2006;7(suppl 3):S19-S26]
Bivalirudin in Acute Coronary Syndromes and Percutaneous Coronary Intervention Anticoagulation in the Cath Lab
The standard of care for patients with acute coronary syndrome is antithrombotic and antiplatelet therapies along with early percutaneous coronary intervention. Because of the limitations of heparin, there has been an interest in direct thrombin inhibitors, such as bivalirudin, which is now the anticoagulant of choice in percutaneous coronary intervention. [Rev Cardiovasc Med. 2006;7(suppl 3):S27-S34]
Economic Implications of Bivalirudin in the Cardiac Catheterization Laboratory Anticoagulation in the Cath Lab
More than 1.2 million percutaneous coronary intervention (PCI) procedures are performed each year in the United States, with average hospital costs of more than $10,000 per procedure. Despite ongoing improvements in device technology and adjunct pharmacology, both ischemic complications (eg, periprocedural myocardial infarction) and bleeding complications remain relatively common and are associated with both increased costs (in the short term) and mortality (in the longer term). Recently, the Randomized Evaluation of PCI Linking Angiomax to Reduced Clinical Events (REPLACE)-2 clinical trial demonstrated that the use of the direct thrombin inhibitor, bivalirudin, with provisional glycoprotein (GP) IIb/IIIa inhibitor for selected patients in place of a conventional anticoagulation strategy of heparin and routine use of a GP IIb/IIIa inhibitor, resulted in comparable rates of ischemic complications and a significant reduction in the frequency of both major and minor bleeding complications. A prospectively designed economic analysis was performed using data from 4651 US patients who participated in REPLACE-2. In this analysis, patients who were assigned to the bivalirudin and provisional GP IIb/IIIa inhibitor strategy had anticoagulation costs during PCI that were approximately $400 per patient lower than those with heparin plus routine GP IIb/IIIa inhibition. Bivalirudin also produced corresponding decreases in total in-hospital costs and aggregate 30-day medical care costs. These cost savings derived both from the lower acquisition cost of the antithrombotic therapy and the reduced rate of bleeding complications, which accounted for approximately 20% of the cost offsets. These results suggest that for patients similar to those studied in REPLACE-2 (ie, low to moderate risk PCI procedures), use of bivalirudin and provisional GP IIb/IIIa inhibition compared with heparin and routine GP IIb/IIIa inhibition can result in similar rates of ischemic complications, reduced bleeding, and substantial cost savings to both hospitals and the healthcare system. Whether these benefits can be extended to higher risk patient subsets including patients with non-ST elevation or ST elevation myocardial infarction is currently under investigation. [Rev Cardiovasc Med. 2006;7(suppl 3):S35-S42]
Future Perspectives on Antithrombin and Antiplatelet Therapies: Novel Antiplatelet and Antithrombin Therapies Anticoagulation in the Cath Lab
The recognition that thrombosis is fundamental to acute coronary syndromes (ACS) has inspired the development of novel therapies to inhibit platelet aggregation and thrombus formation. Several recent advances have been made in the management of patients undergoing percutaneous coronary revascularization and those with acute coronary syndromes to improve early and late clinical outcomes. The research efforts leading to these improvements in care have focused on antiplatelet and anticoagulant therapies coupled with early invasive treatment options. In particular, ongoing clinical trials seek to refine treatment strategies for patients relative to individual risk presentation and to determine the appropriate timing of the administration of antithrombotic therapies and revascularization. Simultaneous with attention toward improving efficacy with novel antithrombotic therapies, however, is an ongoing need to minimize bleeding risk. The purpose of this review is to provide a pathophysiologic rationale for the development of novel antiplatelet and antithrombin therapies in ACS and percutaneous coronary intervention, to examine the results of recent trials, and to present future directions for clinical investigation. [Rev Cardiovasc Med. 2006;7(suppl 3):S43-S52]
Expert Discussion of the Latest Trial Results: Summary Remarks Trial Update
On March 18, 2006, Dr. Gregg W. Stone, Professor of Medicine at Columbia University Medical Center and Chairman of the Cardiovascular Research Foundation in New York, led an expert panel discussion of new data presented at the American College of Cardiology on management of patients with acute coronary syndromes. Following is a summary of the transcript of Dr. Stone’s introduction to this panel discussion, starting with an overview of the ACUITY trial, of which Dr. Stone is the lead investigator. [Rev Cardiovasc Med. 2006;7(suppl 3):S53-S59]