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Letters to the Editor |
Therapeutic Area BioSurgery, Global Clinical R&D, Baxter BioScience, Vienna, Austria
Received 14 September 2007; accepted 21 November 2007.
* Corresponding author. Address: Baxter AG, IZD-Tower, Wagramer Street 17-19, 22-01, A-1220 Vienna, Austria. Tel.: +43 664 812 0209. (Email: raymond_nistor{at}baxter.com).
Key Words: Fibrin sealant • Coronary artery bypass grafting • Myocardial infarction
In 2002 the retrospective observational study of Lamm et al. [1] identified a statistical association (without causality confirmation) between the utilization of fibrin sealant and increased mortality after CABG surgery. He reported 57 fatalities as being possibly related to the application of the fibrin sealant. It was hypothesized that improper thawing and mixing of the sealer components may release free thrombin leading to occlusion of the anastomosed coronary grafts with subsequent myocardial infarction and death.
As the leader of the Baxter Vigilance Team investigating the statistical signals of the publications of Lamm et al. [1] and Goerler et al. [2], I’d like to clarify a few issues raised by these publications and share the facts with your readers. Our investigation has resulted in the 2006 regulatory and pharmacovigilance resolution of this suspected safety signal.
Although we commend Lamm and associates for bringing this important observation to everyone's attention, we’d like to share the conclusions of our scientific investigation to put these observations into the right perspective with regard to therapies that have been repeatedly proven to be effective and safe in CABG surgery in two RCTs in more than 580 patients [3,4].
The parallel Baxter and Paul Ehrlich Institute (PEI) investigations concluded that use of fibrin sealant is a predictor and not the cause of increased mortality, and have ruled out the speculative pathophysiological explanations provided by Lamm et al. In both publications [1,2] the difference in occurrence of myocardial infarction between treatment and control groups was not significant, clearly indicating that graft occlusion is not the reason for the reported difference in mortalities.
To determine if the ‘statistical signal’ vs our investigational evidence requires vigilant corrective action, the findings have been evaluated against the Bradford-Hill causality criteria [5]. Out of the 10 criteria indicating a possible causal relationship, seven criteria were pointing into the direction of a non-causal association. This would favor an increased vigilance, but not restrictive measures. This position is enforced also by the conclusions of Goerler et al. [2].
From the above mentioned investigations it seemed plausible that improper fibrin sealant thawing and also potential misuse of the fibrin sealant could not be completely ruled out. As a consequence Baxter has proactively, and in agreement with key regulatory bodies (PEI, FDA) decided to implement labeling changes to ensure the correct preparation technique and to enforce the existing warning against intravascular application of the fibrin sealant.
Ever since these reports were made public in 2002, we have closely monitored the safety data from clinical trials and from spontaneous safety reports and we cannot report any serious adverse events in either.
In conclusion, the use of fibrin sealant is a predictor and not the cause of increased mortality and the products have been shown repeatedly and across studies to be safe and efficacious with favorable risk–benefit profile. Regardless of these findings application of a fibrin sealant in coronary surgery needs to be always based on a thorough product and application knowledge and a critical individual risk–benefit assessment.
Footnotes
\#9734; The authors of ref. [2] were also invited to comment on this Letter to the Editor but declined the offer.
References
This article has been cited by other articles:
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  P. Lamm and B. Reichart Reply to Nistor Eur. J. Cardiothorac. Surg., February 1, 2008; 33(2): 318 - 318. [Full Text] [PDF]
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