Real-world data on the effectiveness of TYRX and TauroPace for preventing CIED infections.

Am J Cardiovasc Dis 2024;14(4):220-229 www.AJCD.us /ISSN:2160-200X/AJCD0158142 Original Article Real-world data on the effectiveness of TYRX and TauroPace for preventing CIED infections Andrea Messori1, Maria Rita Romeo2, Melania Rivano3, Sabrina Trippoli1 Centro Operativo HTA, Regional Health Service, Regione Toscana, Firenze, Italy; 2Ospedale del Cuore, Fondazione Monasterio, Massa, Italy; 3Scientific Committee, Sifact, Torino, Italy 1 Received May 29, 2024; Accepted August 19, 2024; Epub August 25, 2024; Published August 30, 2024 Abstract: Background: The implantation of cardiac implantable electronic devices (CIEDs) carries a known risk of infection. Two devices (TYRX and TauroPace) have been proposed to reduce this risk. Methods: The aim of our study was to compare the effectiveness of TauroPace and TYRX. Real-world comparative studies were included. Data analysis was based on reconstruction of individual patient data from Kaplan-Meier curves using an artificial intelligence algorithm. The endpoint was CIED infection or systemic infection. Statistical tests included heterogeneity assessment, superiority testing, and non-inferiority testing. The primary outcome measure was the hazard ratio (HR) with confidence interval (CI). Results: Our literature search identified two real-world studies suitable for our analysis. Follow-up was 12 months for TauroPace (654 patients) and 60 months for TYRX (872 patients), with a total of 2,083 controls. There was no heterogeneity among controls. Compared to the pooled control group, patients treated with TYRX or TauroPace had fewer CIED infections (HR, 0.3892; 95% CI, 0.2042-0.7419; P=0.00414; HR, 0.3313; 95% CI, 0.1005-1.0925; P=0.06958, respectively). When testing for non-inferiority of TauroPace vs. TYRX, the comparison yielded a HR of 0.8494 (in favor of TYRX) with a 90% CI of 0.27-2.63; this CI of TauroPace did not meet the non-inferiority criterion set at HR>0.75 (i.e., relative difference ≤25%). Conclusions: Both treatments had some important drawbacks. Regarding TYRX, more selective use in higher-risk patients should be advocated to improve its cost-effectiveness, but robust evidence is still lacking. Regarding TauroPace, our analysis testing for a non-inferiority margin of ≤25% did not meet this demonstration. Keywords: TYRX, TauroPace, taurolidine, CIED infection Introduction Each year, approximately 1.2 to 1.4 million patients worldwide receive a cardiac implantable electronic device (CIED) [1-3]. CIED infection rates have been reported to be increasing for a variety of reasons, including CIED patients having more comorbidities, receiving more complex systems, living longer, and requiring revision procedures. The major complications of CIED include failure of the device to perform as expected and the development of infection. Regarding infection, preventive measures have been proposed, such as TauroPace and TYRX, and in fact the present study was specifically designed to compare these two devices. In addition, among the complications that may occur in the long term (e.g., after 5 years), the need to replace the device or its battery is an important factor. Finally, another fac- tor influencing complications is the type of CIED: while traditional transvenous pacemakers have long been the standard, leadless pacemakers are increasingly being used, and their complication profile differs significantly from that of transvenous pacemakers. With respect to TauroPace and TYRX, there are studies that have monitored the occurrence of infections after more than 6 months and, in some cases, evaluated the long-term efficacy of these devices; however, the cause-and-effect relationship of these preventive measures in the long term remains controversial because the TYRX envelope may not have a significant longterm effect as the device is resorbed after 9 weeks, and a long-term effect of TauroPace is also unlikely. In the field of interventions to reduce the risk of CIED infection, the WRAP-IT trial, published in https://doi.org/10.62347/DSHG1684 Preventing CIED infections the New England Journal of Medicine in 2019 [4], was a milestone in demonstrating that an antimicrobial envelope (developed under the proprietary name TYRX) significantly reduced the risk of CIED infection. The randomized design was the major strength of this study; on the other hand, the high price of TYRX has subsequently been the main barrier to widespread use of this device [5]. Numerous cost-effectiveness studies and national and international guidelines [1, 2] have suggested that more selective use of this device in patients at higher risk of infection could significantly improve the otherwise borderline or clearly unfavorable cost-effectiveness profile of TYRX. In an analysis conducted in the Region of Tuscany (Italy) by the regional HTA body for medical devices, the value-based price of TYRX was estimated at €621, compared to the current market price of over €1,000 [6]. TauroPace™ is an antimicrobial solution designed to remove bacterial contamination from the surface of CIEDs [2, 3]. The active ingredient is taurolidine, an amine derived from the amino acid taurine, which provides broad-spectrum and long-lasting activity. According to the device’s instructions for use, the surface of the CIED should be moistened with the TauroPace solution prior to implantation to create a hostile environment for microbial proliferation. Specifically, the TauroPace™ solution should be applied to the entire surface of the CIED and its components by wiping with sterile, product-soaked gauze pads, taking care to keep them moist prior to implantation. From the perspective of evidence-based methods used in comparative analyses [7-11], the use of appropriate statistical techniques is particularly relevant, especially when the clinical material is based on long-term follow-up. Here, we conducted the present comparative analysis using a new artificial intelligence technique (called the “IPDfromKM” method or the Shiny method [7-11]) to review the current literature and compare the incidence of post-implant CIED infections in patients treated with TYRX or TauroPace in a real-world setting. Only realworld comparative studies evaluating these two devices were included in the analysis. This decision to focus exclusively on real-world studies, as opposed to randomized trials, was made with the understanding that no randomized 221 study of TauroPace has been conducted to date. The IPDfromKM method is a new artificial intelligence tool that reconstructs individual patient data from the graph of Kaplan-Meier curves and allows cross-study comparisons based on reconstructed patients [7-11]. It is a relatively new method for generating original clinical evidence and is particularly suitable for indirect comparisons of time-to-event endpoints, especially those with long follow-up. An advantage of the method is that it takes into account the time at which each event occurred, whereas a stan (...truncated)