HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Investigation of Evidence-based Practice Using Aprotinin:
Statement from The Society of Thoracic Surgeons Aprotinin Task Force

Recently, the FDA and Bayer Pharmaceuticals Corporation agreed to suspend marketing and distribution of the hemostatic drug, aprotinin (Traysolol®). The action came following preliminary results from a Canadian study: Blood conservation using antifibrinolytics: A randomized trial in a cardiac surgery population (BART), that reportedly showed a trend toward increased mortality in patients receiving aprotinin. In response to the FDA action, STS formed an independent Task Force to review recommendations concerning aprotinin use that are found in two STS clinical guidelines: “Aspirin and Other Antiplatelet Agents During Operative Coronary Revascularization” (1), and “Perioperative Blood Transfusion and Blood Conservation in Cardiac Surgery” (2). Both practice guidelines also are posted in the “About STS” section of www.sts.org and on CTSNet for subscribers of The Annals of Thoracic Surgery.

STS clinical guidelines are developed under the auspices of the Evidence Based Surgery Workforce. When the Workforce chooses a guideline topic, a Task Force is formed and clinical evidence, in the form of peer reviewed, published clinical trials, meta-analyses and rarely, case studies, is collected through extensive literature searches. The evidence is evaluated and classified according to the system published by the Joint Task Force for Guidelines of the American College of Cardiology (ACC) and the American Heart Association (AHA) on line at http://circ.ahajournals.org/manual/manual_IIstep6.shtml. Each recommendation within a guideline is followed by a discussion that includes an analysis of any conflicting evidence, as well as qualifying statements and caveats. In the guidelines noted above, Class 1 and Class 2a recommendations were assigned to statements related to administering aprotinin to certain adults undergoing cardiac surgery in which the benefits outweighed the risks. As noted in the guidelines, most of the safety concerns at that time (2005 and early 2007) related to renal dysfunction, not renal failure, and hypersensitivity. The Blood Transfusion guideline also warned that high dose aprotinin should be used with caution, particularly in patients with certain co-morbidities, such as diabetes, pre-existing conditions such as renal dysfunction, and with certain preoperative medications.

The STS guidelines provide treatment recommendations based on the best clinical evidence available at a particular point in time. In keeping with the ACC/AHA guideline writing process and the requirements of the National Guidelines Clearinghouse (www.guidelines.gov), STS is obligated to update guidelines whenever new evidence becomes available and at least every 5 years. New, preliminary data from the BART trial shows an increased mortality risk for patients receiving aprotinin according to the FDA (http://www.fda.gov/bbs/topics/NEWS/2007/NEW01738.html). This risk was not observed in the reported meta-analyses on studies completed before the STS guidelines were published (3-5). In keeping with the STS process for evaluating evidence, it is premature to change the guideline recommendations until a full analysis of the data from the BART study is complete. However, STS will post a warning on the STS Web site that all recommendations concerning aprotinin in our guidelines are “under review” until the results of the analysis of the BART study are available.

Finally, the guidelines noted above were written for adult patients and procedures. Recommendations were based only on studies in adults. Although results from studies specifically testing the safety and efficacy of aprotinin in pediatric patients have been published (6), pediatric patients and procedures were not the subject of the STS guidelines. As such, further updates and revisions to the above guidelines will not include additional recommendations for the pediatric population, which may have different benefits, contraindications, and risk profiles from the adult population.


REFERENCES

1. Ferraris VA, Ferraris SP, Moliterno DJ, Camp P, Walenga JM, Messmore HL, Jeske WP, Edwards FH, Royston D, Shahian DM, Peterson E, Bridges CR, and Despotis G. The Society of Thoracic Surgeons practice guideline series: aspirin and other antiplatelet agents during operative coronary revascularization (executive summary). Ann Thorac Surg. 2005;79:1454-1461.
2. Ferraris VA, Ferraris SP, Saha SP, Hessel EA, 2nd, Haan CK, Royston BD, Bridges CR, Higgins RS, Despotis G, Brown JR, Spiess BD, Shore-Lesserson L, Stafford-Smith M, Mazer CD, Bennett-Guerrero E, Hill SE, and Body S. Perioperative blood transfusion and blood conservation in cardiac surgery: the Society of Thoracic Surgeons and The Society of Cardiovascular Anesthesiologists clinical practice guideline. Ann Thorac Surg. 2007;83:S27-86.
3. Brown JR, Birkmeyer NJ, and O'Connor GT. Aprotinin in cardiac surgery. N Engl J Med. 2006;354:1953-1957; author reply 1953-1957.
4. Henry DA, Moxey AJ, Carless PA, O'Connell D, McClelland B, Henderson KM, Sly K, Laupacis A, and Fergusson D. Anti-fibrinolytic use for minimising perioperative allogeneic blood transfusion. Cochrane Database Syst Rev. 2001;CD001886.
5. Sedrakyan A, Treasure T, and Elefteriades JA. Effect of aprotinin on clinical outcomes in coronary artery bypass graft surgery: a systematic review and meta-analysis of randomized clinical trials. J Thorac Cardiovasc Surg. 2004;128:442-448.
6. Backer CL, Kelle AM, Stewart RD, Suresh SC, Ali FN, Cohn RA, Seshadri R, and Mavroudis C. Aprotinin is safe in pediatric patients undergoing cardiac surgery. J Thorac Cardiovasc Surg. 2007;134:1421-1426; discussion 1426-1428.