Pharmacy & Therapeutics - February 2008 - (Page 98)

Use and Outcomes of Antifibrinolytic Therapy In Patients Undergoing Cardiothoracic Surgery At 20 Academic Medical Centers in the United States Karl Matuszewski, MS, PharmD; Robert Schoenhaus, PharmD; Mar y Ellen Bonk, PharmD; James Lane, PharmD; and Michael Oinonen, PharmD, MPH ABSTRACT Background. Several clinical trials have shown an association between the use of aprotinin in cardiothoracic surgery (CTS) patients and an increased risk of adverse renal, cardiovascular, and cerebrovascular events. Other antifibrinolytic agents—aminocaproic acid (AA) and tranexamic acid (TA)— have not shown elevated risks. Using a large administrative data set, we sought to examine these findings. Methods. In our obser vational database study of CTS patients who were discharged from 20 academic medical centers from October 2002 through September 2005, we assessed the use of antifibrinolytic therapy on select patient outcomes using descriptive and inferential statistics to compare the various groups. Results. For the CTS patients, AA was used in 9,751 (15.5% of patients) and aprotinin was used in 6,855 (10.9% of patients). Only 17 patients from four hospitals received TA; therefore, TA was excluded from further analysis. A quarterly analysis showed a slow decline in the use of AA, with a gradual increase in the use of aprotinin over the study time period. Variation by hospital using each option was considerable (range, 0%–50%). Statistically significant differences in mortality rates (P < 0.001) occurred with AA (2.6%), aprotinin (5.2%), and control patients (n = 46,123), who did not use any antifibrinolytic agents (3.9%). Rates of acute renal failure were 6.2% with AA, 10.9% with aprotinin, and 6.1% in controls; hemodialysis rates were 2.8%, 6.4%, and 2.6%, respectively. Postoperative acute myocardial infarction occurred in only two cases of patients receiving AA, in none of those using aprotinin, and in 63 controls. Conclusion. Although the use of aprotinin has been increasing, compared with AA, the overall use of antifibrinolytic agents in patients undergoing CTS has remained relatively stable over a three-year period, at under 30%. Significant differences in patient outcomes were observed between the two treatment groups. Given the growing body of evidence for the use of antifibrinolytic therapy, hospitals might be best served by examining existing patterns of use and by instituting restrictions of aprotinin for patients facing an increased risk for bleeding during CTS. Key words: drug safety, aprotinin, antifibrinolytic therapy, database review INTRODUCTION For many years, the prevention of major blood loss in highrisk patients needing cardiothoracic surgery (CTS) has been a well-accepted use of antifibrinolytic drug therapy.1 The individual pharmacodynamic effects of each of these agents are well known, but few comparative trials of long-term safety and effectiveness have been conducted. The most expensive agent in this class, aprotinin (Trasylol, Bayer), has become the subject of numerous public medical alerts warning of an increased incidence of renal failure and mortality,2–5 subpar or similar clinical performance compared with alternative antifibrinolytic agents,6,7 and deleterious drug8 and laboratory test9 interactions. However, the authors of a 2004 meta-analysis concluded that it was both safe and effective.10 Background Aprotinin is a naturally occurring proteolytic enzyme inhibitor within the class of drugs known as serine protease inhibitors. It was approved by the FDA in 1993 for prophylactic use to reduce perioperative blood loss and the need for blood transfusion in patients undergoing cardiopulmonary bypass in the course of coronar y arter y bypass grafting (CABG). Two other antifibrinolytic agents—aminocaproic acid (AA) and tranexamic acid (TA)—have also been used in an offlabel fashion for these purposes.1,11 In early 2006, the use of aprotinin during CABG surgery was questioned because of its potential to cause adverse effects. In The results of this paper were presented at the 27th annual meeting of the American College of Clinical Pharmacy in October 2006 in St. Louis, Missouri. Disclosure: No external financial support was received for the conduct of this study. Dr. Matuszewski is Senior Director of the Clinical Knowledge Service, Clinical Practice Advancement Center; Dr. Bonk is Manager of the Drug Information Group; and Dr. Oinonen is Director, Clinical Data Base/Clinical Resource Manager and Data Quality, Clinical Data and Informatics, all at at the University HealthSystem Consortium in Oak Brook, Illinois. Dr. Schoenhaus is a Pharmacist Specialist in Pharmacoeconomics; Medication Use Evaluation Coordinator; and Assistant Clinical Professor at the University of California, San Diego, School of Pharmacy. Dr. Lane is a Pharmacist Specialist in Pharmacokinetics at UCSD Medical Center, Hillcrest, Department of Pharmacy, in San Diego; and Associate Clinical Professor in Health Sciences at the UCSD Skaggs School of Pharmacy and Pharmaceutical Sciences in La Jolla, California. Accepted for rapid publication January 14, 2008. 98 P&T® • February 2008 • Vol. 33 No. 2

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Pharmacy & Therapeutics - February 2008 Contents Editorial Medication Errors Prescription: Washington The Language of (Forgive Us) Change, As P&T Enters the Digital Age New Drugs/Drug News/New Medical Devices Drug Forecast Use and Outcomes of Antifibrinolytic Therapy in Patients Undergoing Cardiothoracic Surgery at 20 Academic Medical Centers in the United States Evaluation of the Management of Acute Venous Thromboembolism and Its Outcomes: One Institution's Experience American Society of Hematology, 49th Annual Meeting Pharmaceutical Approval Update

Pharmacy & Therapeutics - February 2008

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