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Ann Thorac Surg 2004;77:642-643
© 2004 The Society of Thoracic Surgeons
Department of Anesthesiology Mount Sinai School of Medicine One Gustave L. Levy Place Box 1010 New York, NY 10029 USA
Department of Anesthesiology Mount Sinai School of Medicine One Gustave L. Levy Place Box 1010 New York, NY 10029 USA
Mount Sinai School of Medicine Department of Cardiothoracic Surgery Mount Sinai Medical Center 1190 Fifth Ave New York, NY 10029 USA
e-mail: linda.shore{at}mssm.edu
e-mail: david.reich{at}msnyuhealth.org
e-mail: david.adams{at}mountsinai.org
Economic analyses that evaluate the short- and long-term implications of costly perioperative therapies are a sound method of determining the relative merits of these interventions. This study by Smith et al utilizes an elegant mathematical model of estimating the cost-effectiveness of aprotinin therapy in short- and long-term perspectives. This complex analysis may be summarized as follows:
1. FDA-sponored trials demonstrate superiority of full-dose aprotinin with respect to bleeding and stroke rate in reoperations.
2. Using cost-analyses derived from index data from Duke University Medical Center, a mathematical model was developed to estimate total perioperative costs (including the long-term costs of complications) of cardiac surgical procedures.
3. Application of this model led to the conclusion that aprotinin therapy reduced total cost in repeat cardiac operations, and was cost-neutral in primary operations.The authors have provided a comprehensive description of their methodology, as well as the limitations of their study. We will elaborate on these and several other points to place this important publication into context.
The current standard of care for patients undergoing repeat cardiac surgery includes the selection of either aprotinin or a synthetic antifibrinolytic agent [1,2], assuming there is no contraindication to such use. Thus the comparison of aprotinin with placebo in this context is not clinically meaningful. The literature supporting the positive hemostatic effects of antifibrinolytic therapy relative to placebo derives from a high level of evidence from prospective randomized studies and meta-analyses [3–5]. As noted by Smith et al, comparisons of aprotinin against the synthetic anti-fibrinolytics are most relevant clinically, but their ability to perform an economic analysis was limited by the relative paucity of comparative trials in high-risk patients.
It is not surprising that Smith et al found aprotinin to be cost-neutral in primary cardiac operations. This is a low-risk population in which bleeding and transfusions are not prevalent. Casati et al demonstrated that in a low risk population of 1000 patients, differences between agents are difficult to demonstrate [6]. In routine primary coronary artery bypass grafting surgery, the use of antifibrinolytic agents is clinician and institution dependent; there have yet been no cost-benefit analyses evaluating this issue. However, if some form of anti-fibrinolysis is desired, the lower cost of the synthetic antifibrinolytics represents at least an economic advantage.
In a multicenter trial comparing aprotinin to epsilon-aminocaproic acid in repeat cardiac surgery, Bennett-Guerro et al demonstrated that aprotinin was more effective in reducing transfusions; however, epsilon-aminocaproic acid was more cost-effective than aprotinin when the costs of drug, transfusion-related resources, and morbidity were considered [7]. The cost-savings potentially attributable to stroke reduction, however, were not considered at that time.
The ability of aprotinin to reduce the incidence of ischemic stroke due to its antiinflammatory properties remains a controversial point. Prospective evidence that aprotinin reduces the risk of stroke in repeat cardiac surgery is derived predominantly from a single study by Levy et al with a relatively small number of subjects [8]. That study and other trials that were designated to measure the hemostatic effects of aprotinin did not stratify group assignment based upon acknowledged risk factors for stroke. Neither did they use a standardized or uniform definition for postoperative stroke among trials. A retrospective investigation at a single institution that did control for stroke risk factors found a lower incidence of stroke in patients receiving full-dose aprotinin (0 out of 26), compared with half-dose aprotinin (15 out of 67) and no aprotinin (9 out of 56) [9]. The definitive answer to this question, however, awaits prospective randomized trials specifically designed to measure neurological outcomes by virtue of stratification of group assignment based upon stroke risk factors. There is as yet no level A evidence that aprotinin reduces perioperative stroke in repeat cardiac surgery nor a convincing demonstration that the proposed mechanism of action is directly responsible for the effect. Any potential cost-savings should be considered hypothesis-generating at this time.
In summary, an elegant study by Smith et al has demonstrated that aprotinin use may be cost-neutral in primary operations and cost-beneficial in repeat cardiac surgery. The potential for similar or superior cost effectiveness using less expensive synthetic antifibrinolytic therapy is an intriguing question that the current investigation does not address. Nevertheless, the authors' use of cost modeling is an exemplary means of analyzing the long-term benefits of aprotinin and other expensive perioperative therapies.
| Drs Smith and Nadel disclose that they have a financial relationship with Bayer Corp.
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References
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